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Chemical modification of active scaffolds from natural products has gained interest in pharmaceutical industries. Nevertheless, the metabolites extraction is time-consuming while the lead is frequently mismatched with the receptor. Here, the diazo coupling approach was introduced to generate a series of vanillin derivatives featuring halogenated azo dyes ( 1a-h ). The vanillin derivatives showed effective inhibition of S. aureus (7-9 mm) and E. coli (7-8 mm) compared to the parent vanillin, while 1b had the highest inhibition zone (9 mm) against S. aureus comparable to the reference ampicillin. The presence of N = N, C = O, -OH, -OCH3 and halogens established strategic binding interactions with the receptor. The potential vanillin-azo as an antimicrobial drug was supported by in silico docking with penicillin-binding proteins and DFT (using Gaussian 09) with binding affinity -7.5 kcal/mol and energy gap (Egap) 3.77 eV, respectively. This study represents a significant advancement in drug discovery for effective antibiotics with excellent properties.

Novel strategies against parasitic infections are of great importance. Here, we describe a G4 DNA ligand with subnanomolar antiparasitic activity against T. brucei and a remarkable selectivity index (IC 50 MRC-5/ T. brucei ) of 2285-fold. We also correlate the impact of small structural changes to G4 binding activity and antiparasitic activity.

New azo Schiff base disperse dyes based on a chromene moiety were synthesized by reacting (2-amino-7-hydroxy-4-(4-methoxyphenyl)-4 H-chromene-3 carbonitrile) and(2-amino-4-(3,4-dimethoxyphenyl)-7-hydroxy-4 H-chromene-3-carbonitrile), with vanillin and ninhydrin, producing new chromene Schiff base derivatives, which in turn were coupled with 2-chloro-4-nitroaniline diazonium salt to give new 4 azo disperse dyes (1-4). The structures of the prepared dyes were confirmed using elemental analysis, 1 HNMR spectroscopy, mass spectrometry, and IR. The synthesized dyes were applied to polyester and nylon fabrics using different dyeing techniques: high temperature- high pressure, and ultrasonic dyeing methods. The highest K/S values for all investigated dyes were achieved usinga high temperature-high pressure dyeing technique. Also, the color reflectance of all synthesized dyes with different dyeing shades (1%, 2%, and 3%) was obtained. The fastness properties of the dyed samples using the investigated dyes showed good color fastness toward light, washing, rubbing, and perspiration fastness. The presence of a chromene moiety and Schiff base in the investigated dyes promotes a higher antimicrobial activity on nylon and polyester fabrics against all tested bacteria (E. coli gram-negative and Staphylococcus aureus gram-positive) and two fungi, Aspergillus Niger and Candida albicans., (© 2024. The Author(s).)

The present work involves the synthesis of novel dispersed mono-azo dyes using different coupling components and 2-methoxy-5-nitro aniline as amine through a simple and convenient diazo-coupling method. The structures of the newly synthesized mono azo dyes were confirmed by using various spectral techniques such as 1 H NMR, Fourier transform infrared, and high-resolution mass spectrometry. At room temperature, the electronic absorption spectra and fluorescence spectra of the synthesized mono azo dyes were recorded with different solvents. The global reactive parameters for the synthesized azo molecules were evaluated by performing density functional theory through the 6-311++G (d, p) basis set. The anti-microbial activities for the synthesized azo compounds were carried out, and the compounds G1 and G2 exhibited good antibacterial and anti-fungal activities. The in silico molecular docking studies of the azo molecules revealed that all the compounds exhibited extraordinary binding affinity as that of the standard drug. Further, the anti-tuberculosis study against the Mycobacterium tuberculosis for the synthesized azo dyes was evaluated, and from the results, it was revealed that the compound G4 showed good sensitivity among the other synthesized azo compounds., (© 2024 John Wiley & Sons Ltd.)

2-((1-(4-((2,4,6-trioxohexahydropyrimidin-5-yl)diazenyl) phenyl) ethylidene) amino) benzoic acid (H 3 L), and its V(IV), Co(II), Ni(II), Cu(II), Pd(II) and Ag(I) chelates were synthesized. They were defined using multiple spectral and analytical techniques. With the exception of Ag(I) chelate, all chelates possessed non-electrolytic character. Square pyramidal shape was proposed for V(IV) chelate and Square planar for the other chelates. The analysis of functional group bands of H 3 L and its coordination compounds alludes that H 3 L chelated as neutral tetradentate via nitrogen atoms of azo and azomethine groups, oxygen atom of carbonyl of barbituric acid and OH of the carboxylic group. TG/DTG predicted the thermal behaviors of all compounds. The antibacterial activity of H 3 L and its coordination compounds was conducted against Proteus mirabilis at concentrations of 250, 500, and 1000 µg/mL. Ag(I) at 1000 µg/mL, showed the most inhibiting potency against P. mirabilis and registered zone of inhibition of 28.33 ± 0.84 mm and highest biofilm inhibition of 70.31%. At 50 Gy of gamma irradiation, the reducing effect of Ag(I) chelate was improved. The protein interruption of P. mirabilis was greatly interrupted by increasing the concentration of the chaletes. Also, Ag(I) showed the highest cytotoxicity with IC 50 value of 11.5 µg/ mL. The novelty of this study is the synthesis of a new azo-Schiff base and this is almost the first publication of the effect of azo-Schiff ligands against that bacterial strain P. mirabilis., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Photo-switchable nuclear receptor modulators ("photohormones") enable spatial and temporal control over transcription factor activity and are valuable precision tools for biological studies. We have developed a new photohormone chemotype by incorporating a light-switchable motif in the scaffold of a cinalukast-derived PPARα ligand and tuned light-controlled activity by systematic structural variation. An optimized photohormone exhibited PPARα agonism in its light-induced (Z)-configuration and strong selectivity over related lipid-activated transcription factors representing a valuable addition to the collection of light-controlled tools to study nuclear receptor activity., (© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

A set of arylazopyrazole-based inhibitors targeting the mitotic motor protein CENP-E was discovered through the chemical platform using the quantitative cyclization of 1,3-diketone intermediate with various hydrazines under mild conditions. Through this efficient platform, the structure-activity relationship pertaining to the pyrazole photoswitch in photoswitchable CENP-E inhibitors not only in vitro but also in cells was successfully clarified., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

G-quadruplexes (G4s) are important therapeutic and photopharmacological targets in cancer research. Small-molecule ligands targeting G4s offer a promising strategy to block DNA transactions and induce genetic instability in cancer cells. While numerous G4-ligands have been reported, relatively few examples exist of compounds whose G4-interactive binding properties can be modulated using light. Herein, we report the photophysical characterization of a novel ortho -fluoroazobenzene derivative, Py-Azo4F-3N , that undergoes reversible two-way isomerization upon visible light exposure. Using a combination of biophysical techniques, including affinity and selectivity assays, structural and computational analysis, and cytotoxicity experiments in cancer cell lines, we carefully characterized the G4-interactive binding properties of both isomers. We identify the trans isomer as the most promising form of interacting and stabilizing G4s, enhancing their ablation capability in cancer cells. Our research highlights the importance of light-responsive molecules in achieving precise control over G4 structures, demonstrating their potential in innovative anticancer strategies.

Photoregulation of biomolecules has become crucial tools in chemical biology, because light enables access under mild conditions and with delicate spatiotemporal control. The control of enzyme activity in a reversible way is a challenge. To achieve it, a facile approach is to use photoswitchable inhibitors. This review highlights recent progress in photoswitchable inhibitors based on azobenzenes units. The progress suggests that the incorporation of an azobenzene unit to a known inhibitor is an effective method for preparing a photoswitchable inhibitor, and with these photoswitchable inhibitors, the activity of enzymes can be regulated by optical control, which is valuable in both basic science and therapeutic applications.

NMDA receptors (NMDARs) are glutamate-gated ion channels playing a central role in synaptic transmission and plasticity. NMDAR dysregulation is linked to various neuropsychiatric disorders. This is particularly true for GluN2B-containing NMDARs (GluN2B-NMDARs), which have major pro-cognitive, but also pro-excitotoxic roles, although their exact involvement in these processes remains debated. Traditional GluN2B-selective antagonists suffer from slow and irreversible effects, limiting their use in native tissues. We therefore developed OptoNAM-3, a photoswitchable negative allosteric modulator selective for GluN2B-NMDARs. OptoNAM-3 provided light-induced reversible inhibition of GluN2B-NMDAR activity with precise temporal control both in vitro and in vivo on the behavior of freely moving Xenopus tadpoles. When bound to GluN2B-NMDARs, OptoNAM-3 displayed remarkable red-shifting of its photoswitching properties allowing the use of blue light instead of UV light to turn-off its activity, which we attributed to geometric constraints imposed by the binding site onto the azobenzene moiety of the ligand. This study therefore highlights the importance of the binding site in shaping the photochemical properties of azobenzene-based photoswitches. In addition, by enabling selective, fast, and reversible photocontrol of native GluN2B-NMDARs with in vivo compatible photochemical properties (visible light), OptoNAM-3 should be a useful tool for the investigation of the GluN2B-NMDAR physiology in native tissues.

Photoswitchable lipids, particularly azobenzene-derivatized phosphatidylcholine (azoPC) lipids, offer a unique mechanism for reversible modification of membrane properties upon exposure to ultraviolet (UV) radiation. Through all-atom molecular dynamics simulations, we explore how UV irradiation-induced trans-to-cis photoisomerization (TCPI) of AzoPC lipid influences the structure and dynamics of a lipid membrane, composed of dipalmitoylphosphatidylcholine (DPPC) and cholesterol with similar composition to that of the DOXIL®. Structural and dynamical analyses of two states of the membrane, 'dark' state (containing cis-azoPC lipid) and 'bright' state (containing 85 % cis-azoPC and 15 % trans-azoPC lipids) reveal that the TCPI reduces membrane packing density and increases diffusivity of lipids. We have demonstrated an enhanced intercalation of doxorubicin (DOX), an anticancer drug, in the 'bright' state of the membrane compared to that in the 'dark' state. This study - elucidating the complex interplay between lipid composition, photoswitching, and lipid-drug interactions - contributes to the design of lipid-based systems for targeted drug delivery and biomedical applications., (© 2024 Wiley-VCH GmbH.)

The conventional approach to developing light-sensitive glycosidase activity regulators, involving the combination of a glycomimetic moiety and a photoactive azobenzene module, results in conjugates with differences in glycosidase inhibitory activity between the interchangeable E and Z-isomers at the azo group that are generally below one-order of magnitude. In this study, we have exploited the chemical mimic character of sp 2 -iminosugars to access photoswitchable p- and o-azobenzene α-O-glycosides based on the gluco-configured representative ONJ. Notably, we achieved remarkably high switching factors for glycosidase inhibition, favoring either the E- or Z-isomer depending on the aglycone structure. Our data also indicate a correlation between the isomeric state of the azobenzene module and the selectivity towards α- and β-glucosidase isoenzymes. The most effective derivative reached over a 10 3 -fold higher inhibitory potency towards human β-glucocerebrosidase in the Z as compared with the E isomeric form. This sharp contrast is compatible with ex-vivo activation and programmed self-deactivation at physiological temperatures, positioning it as a prime candidate for pharmacological chaperone therapy in Gaucher disease. Additionally, our results illustrate that chemical tailoring enables the engineering of photocommutators with the ability to toggle inhibition between α- and β-glucosidase enzymes in a reversible manner, thus expanding the versatility and potential therapeutic applications of this approach., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Hepatitis C virus (HCV) is a global health concern and the NS5B RNA-dependent RNA polymerase (RdRp) of HCV is an attractive target for drug discovery due to its role in viral replication. This study focuses on NS5B thumb site II inhibitors, specifically phenylalanine derivatives, and explores bioisosteric replacement and prodrug strategies to overcome limitations associated with carboxylic acid functionality. The synthesized compounds demonstrated antiviral activity, with compound 6d showing the most potent activity with an EC 50 value of 3.717 μM. The hydroxamidine derivatives 7a-d showed EC 50 values ranging from 3.9 μM to 11.3 μM. However, the acidic heterocyclic derivatives containing the oxadiazolone (8a-d) and oxadiazolethione (9a-d) rings did not exhibit measurable activity. A methylated heterocycle 10b showed a hint of activity at 8.09 μM. The pivaloyloxymethyl derivatives 11a and 11b did not show antiviral activity. Further studies are warranted to fully understand the effects of these modifications and to explore additional strategies for developing novel therapeutic options for HCV., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Cardiovascular diseases pose a significant global health challenge, contributing to high mortality rates and impacting overall well-being and quality of life. Nitric oxide (NO) plays a pivotal role as a vasodilator, regulating blood pressure and enhancing blood flow-crucial elements in preventing cardiovascular diseases, making it a prime therapeutic target. Herein, metal-based nanozymes (NZs) designed to induce NO release from both endogenous and exogenous NO-donors are investigated. Successful synthesis of gold, platinum (Pt) and cerium oxide NZs is achieved, with all three NZs demonstrating the ability to catalyze the NO release from various NO sources, namely S-nitrosothiols and diazeniumdiolates. Pt-NZs exhibit the strongest performance among the three NZ types. Further exploration involved investigating encapsulation and coating techniques using poly(lactic-co-glycolic acid) nanoparticles as experimental carriers for Pt-NZs. Both strategies showed efficiency in serving as platforms for Pt-NZs, successfully showing the ability to trigger NO release., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. The funders had no role in the design of the study nor in the decision to publish the results., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Enzyme-responsive self-assembled nanostructures for drug delivery applications have gained a lot of attention, as enzymes exhibit dysregulation in many disease-associated microenvironments. Azoreductase enzyme levels are strongly elevated in many tumor tissues; hence, here, we exploited the altered enzyme activity of the azoreductase enzyme and designed a main-chain azobenzene-based amphiphilic polyurethane, which self-assembles into a vesicular nanostructure and is programmed to disassemble in response to a specific enzyme, azoreductase, with the help of the nicotinamide adenine dinucleotide phosphate (NADPH) coenzyme in the hypoxic environment of solid tumors. The vesicular nanostructure sequesters, stabilizes the hydrophobic anticancer drug, and releases the drug in a controlled fashion in response to enzyme-triggered degradation of azo-bonds and disruption of vesicular assembly. The biological evaluation revealed tumor extracellular matrix pH-induced surface charge modulation, selective activated cellular uptake to azoreductase overexpressed lung cancer cells (A549), and the release of the anticancer drug followed by cell death. In contrast, the benign nature of the drug-loaded vesicular nanostructure toward normal cells (H9c2) suggested excellent cell specificity. We envision that the main-chain azobenzene-based polyurethane discussed in this manuscript could be considered as a possible selective chemotherapeutic cargo against the azoreductase overexpressed cancer cells while shielding the normal cells from off-target toxicity.

Biofilm is a community of microorganisms attached to the substrate and plays a significant role in microbial pathogenesis and medical device-related infection. Pseudomonas aeruginosa (PA) is a highly infectious gram-negative opportunistic biofilm-forming bacterium with high antibiotic resistance. Several reports underscore the antimicrobial activity of natural and synthetic food coloring agents, including carmoisine, turmeric dye, red amaranth dye, and phloxine B. However, their ability to suppress the PA biofilm is not clearly understood. Carmoisine is a red-colored synthetic azo dye containing naphthalene subunits and sulfonic groups and is widely used as a food coloring agent. This study investigated the antibiofilm potential and possible mechanism of biofilm inhibition by carmoisine against PA. Computational studies through molecular docking revealed that carmoisine strongly binds to QS regulator LasR (-12.7) and relatively less strongly but significantly with WspR (-6.9). Further analysis of the docked LasR-carmoisine complex using 100 ns MD simulation (Desmond, Schrödinger) validated the bonding strength and stability. Crystal violet assay, triphenyl tetrazolium chloride salt assay, and confocal microscopic studies were adopted for biofilm quantification, and the results indicated the dose-dependent antibiofilm activity of carmoisine against PA. We hypothesise that the carmoisine-mediated reduction of biofilm in PA is due to its interaction with LasR and interference with the QS system. The computational and biochemical analysis of another compound, 1,2-naphthoquinone-4-sulphonic acid, reiterated the role of the naphthalene ring in biofilm inhibition. Hence, this work will pave the way for the future discovery of antibiofilm drugs based on naphthalene ring-based lead compounds.Communicated by Ramaswamy H. Sarma.

This study introduces (S)-Opto-prop-2, a second-generation photoswitchable ligand designed for precise modulation of β 2 -adrenoceptor (β 2 AR). Synthesised by incorporating an azobenzene moiety with propranolol, (S)-Opto-prop-2 exhibited a high PSS cis (photostationary state for cis isomer) percentage (∼90 %) and a favourable half-life (>10 days), facilitating diverse bioassay measurements. In vitro, the cis-isomer displayed substantially higher β 2 AR binding affinity than the trans-isomer (1000-fold), making (S)-Opto-prop-2 one of the best photoswitchable GPCR (G protein-coupled receptor) ligands reported so far. Molecular docking of (S)-Opto-prop-2 in the X-ray structure of propranolol-bound β 2 AR followed by site-directed mutagenesis studies, identified D113 3.32 , N312 7.39 and F289 6.51 as crucial residues that contribute to ligand-receptor interactions at the molecular level. In vivo efficacy was assessed using a rabbit ocular hypertension model, revealing that the cis isomer mimicked propranolol's effects in reducing intraocular pressure, while the trans isomer was inactive. Dynamic optical modulation of β 2 AR by (S)-Opto-prop-2 was demonstrated in two different cAMP bioassays and using live-cell confocal imaging, indicating reversible and dynamic control of β 2 AR activity using the new photopharmacology tool. In conclusion, (S)-Opto-prop-2 emerges as a promising photoswitchable ligand for precise and reversible β 2 AR modulation with light. The new tool shows superior cis-on binding affinity, one of the largest reported differences in affinity (1000-fold) between its two configurations, in vivo efficacy, and dynamic modulation. This study contributes valuable insights into the evolving field of photopharmacology, offering a potential avenue for targeted therapy in β 2 AR-associated pathologies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Inhibiting the PD-1/PD-L1 protein-protein interaction is a key immunotherapy for cancer. Antibodies dominate the clinical space but are costly, with limited applicability and immune side effects. We developed a photo-controlled azobenzene peptide that selectively inhibits the PD-1/PD-L1 interaction when in the cis isomer only. Activity is demonstrated in in vitro and cellular assays.

Water pollution and antimicrobial resistance (AMR) have become two global threats; 80% of diseases and 50% of child deaths are due to poor water quality. In this study, hydrothermal processing was employed to manufacture manganese oxide nanorods. Silver dopant was deposited on the surface of manganese oxide. XRD diffractogram confirmed the facile synthesis of Ag/Mn 2 O 3 nanocomposite. XPS survey analysis demonstrated silver content of 9.43 atom %. Photocatalytic measurements demonstrated the outstanding efficiency of the Ag-Mn 2 O 3 compared to virgin oxide particles under visible radiation. Degradation efficiencies Mn 2 O 3 and Ag/Mn 2 O 3 on methyl orange (MO) dye was found to be 53% and 85% under visible spectrum. Silver dopant was found to decrease the binding energy of valence electrons; this action could support electron-hole pair generation under visible spectrum and could promote catalytic performance. Ag/Mn 2 O 3 NPs demonstrated most effective performance (95% removal efficiency) at pH 3; this could be ascribed to the electrostatic attraction between positively charged catalyst and the negatively charged MO. Ag/Mn 2 O 3 demonstrated enhanced antibacterial activity against Gram-positive Staphylococcus aureus (S. aureus) (19 mm ZOI), and Gram-negative Escherichia coli (E. coli) (22 mm ZOI) respectively; the developed nanocomposite demonstrated advanced anti-film activity with inhibition percentage of 95.5% against E. coli followed by 89.5% against S. aureus., (© 2024. The Author(s).)

We developed a centromere-associated protein E (CENP-E) inhibitor employing trans to cis photoisomerization with 405 nm visible light illumination and fast thermal relaxation. This photoswitching characteristic of the inhibitor enabled selective blockage or release of the motion of particular chromosomes within a single mitotic cell. Using this technique, we successfully demonstrated targeted chromosome gain and loss in daughter cells by introducing asymmetric chromosome segregation.

Azopolymers are light-responsive materials that hold promise to transform in vitro cell culture systems. Through precise light illumination, they facilitate substrate pattern formation and erasure, allowing for the dynamic control and creation of active interfaces between cells and materials. However, these materials exhibit a tendency to locally detach from the supporting glass in the presence of aqueous solutions, such as cell culture media, due to the formation of blisters, which are liquid-filled cavities generated at the azopolymer film-glass interface. These blisters impede precise structurization of the surface of the azomaterial, limiting their usage for surface photoactivation in the presence of cells. In this study, we present a cost-effective and easily implementable method to improve the azopolymer-glass interface stability through silane functionalization of the glass substrate. This method proved to be efficient in preventing blister formation, thereby enabling the dynamic modulation of the azopolymer surface in situ for live-cell experiments. Furthermore, we proved that the light-illumination conditions used to induce azopolymer surface variations do not induce phototoxic effects. Consequently, this approach facilitates the development of a photoswitchable azopolymer cell culture platform for studying the impact of multiple in situ inscription and erasure cycles on cell functions while maintaining a physiological wet microenvironment.

Photopharmacology can be implemented in a way of regulating drug activities by light-controlling the molecular configuations. Three photochromic ligands (PCLs) that bind on one or two sites of GABARs and nAChRs were reported here. These multiphoton PCLs, including FIP-AB-FIP, IMI-AB-FIP, and IMI-AB-IMI, are constructed with an azobenzene (AB) bridge that covalently connects two fipronil (FIP) and imidacloprid (IMI) molecules. Interestingly, the three PCLs as well as FIP and IMI showed great insecticidal activities against Aedes albopictus larvae and Aphis craccivora . IMI-AB-FIP in both trans / cis isomers can be reversibly interconverted depending on light, accompanied by insecticidal activity decrease or increase by 1.5-2.3 folds. In addition, IMI-AB-FIP displayed synergistic effects against A. craccivora (LC 50, IMI-AB-FIP = 14.84-22.10 μM, LC 50, IMI-AB-IMI = 210.52-266.63 μM, LC 50, and FIP-AB-FIP = 36.25-51.04 μM), mainly resulting from a conceivable reason for simultaneous targeting on both GABARs and nAChRs. Furthermore, modulations of wiggler-swimming behaviors and cockroach neuron function were conducted and the results indirectly demonstrated the ligand-receptor interactions. In other words, real-time regulations of receptors and insect behaviors can be spatiotemporally achieved by our two-photon PCLs using light.

Nanotechnology and nanoparticles have gained massive attention in the scientific community in recent years due to their valuable properties. Among various AgNPs synthesis methods, microbial approaches offer distinct advantages in terms of cost-effectiveness, biocompatibility, and eco-friendliness. In the present research work, investigators have synthesized three different types of silver nanoparticles (AgNPs), namely AgNPs-K, AgNPs-M, and AgNPs-E, by using Klebsiella pneumoniae (MBC34), Micrococcus luteus (MBC23), and Enterobacter aerogenes (MBX6), respectively. The morphological, chemical, and elemental features of the synthesized AgNPs were analyzed by using UV-Vis spectroscopy (UV-Vis), Fourier transform-infrared spectroscopy (FTIR), X-ray diffraction (XRD), field emission scanning electron microscope (FESEM) and energy-dispersive spectroscopy (EDX). UV-Vis absorbance peaks were obtained at 475, 428, and 503 nm for AgNPs-K, AgNPs-M, and AgNPs-E, respectively. The XRD analysis confirmed the crystalline nature of the synthesized AgNPs, having peaks at 26.2°, 32.1°, and 47.2°. At the same time, the FTIR showed bands at 599, 963, 1,693, 2,299, 2,891, and 3,780 cm -1 for all the types of AgNPs indicating the presence of bacterial biomolecules with the developed AgNPs. The size and morphology of the AgNPs varied from 10 nm to several microns and exhibited spherical to porous sheets-like structures. The percentage of Ag varied from 37.8% (wt.%) to 61.6%, i.e ., highest in AgNPs-K and lowest in AgNPs-M. Furthermore, the synthesized AgNPs exhibited potential for environmental remediation, with AgNPs-M exhibiting the highest removal efficiency (19.24% at 120 min) for methyl orange dye in simulated wastewater. Further, all three types of AgNPs were evaluated for the removal of methyl orange dye from the simulated wastewater, where the highest dye removal percentage was 19.24% at 120 min by AgNPs-M. Antibacterial potential of the synthesized AgNPs assessment against both Gram-positive (GPB) Bacillus subtilis (MBC23), B. cereus (MBC24), and Gram-negative bacteria Enterococcus faecalis (MBP13) revealed promising results, with AgNPs-M, exhibiting the largest zone of inhibition (12 mm) against GPB B. megaterium . Such investigation exhibits the potential of the bacteria for the synthesis of AgNPs with diverse morphology and potential applications in environmental remediation and antibacterial therapy-based synthesis of AgNPs., Competing Interests: The authors declare that they have no competing interests., (© 2024 Patel et al.)

The present work elicits a novel approach to combating COVID-19 by synthesizing a series of azo-anchored 3,4-dihydroimidazo[4,5-b]indole derivatives. The envisaged methodology involves the L-proline-catalyzed condensation of para-amino-functionalized azo benzene, indoline-2,3-dione, and ammonium acetate precursors with pertinent aryl aldehyde derivatives under ultrasonic conditions. The structures of synthesized compounds were corroborated through FT-IR, 1 H NMR, 13 C NMR, and mass analysis data. Molecular docking studies assessed the inhibitory potential of these compounds against the main protease (M pro ) of SARS-CoV-2. Remarkably, in silico investigations revealed significant inhibitory action surpassing standard drugs such as Remdesivir, Paxlovid, Molnupiravir, Chloroquine, Hydroxychloroquine (HCQ), and (N3), an irreversible Michael acceptor inhibitor. Furthermore, the highly active compound was also screened for cytotoxicity activity against HEK-293 cells and exhibited minimal toxicity across a range of concentrations, affirming its favorable safety profile and potential suitability. The pharmacokinetic properties (ADME) of the synthesized compounds have also been deliberated. This study paves the way for in vitro and in vivo testing of these scaffolds in the ongoing battle against SARS-CoV-2., (© 2024. The Author(s).)

PD-1 blockade is a first-line treatment for recurrent/metastatic cervical cancer but benefits only a small number of patients due to low preexisting tumor immunogenicity. Using immunogenic cell death (ICD) inducers is a promising strategy for improving immunotherapy, but these compounds are limited by the hypoxic environment of solid tumors. To overcome this issue, the nanosensitizer AIBA@MSNs were designed based on sonodynamic therapy (SDT), which induces tumor cell death under hypoxic conditions through azo free radicals in a method of nonoxygen radicals. Mechanistically, the azo free radicals disrupt both the structure and function of tumor mitochondria by reversing the mitochondrial membrane potential and facilitating the collapse of electron transport chain complexes. More importantly, the AIBA@MSN-based SDT serves as an effective ICD inducer and improves the antitumor immune capacity. The combination of an AIBA@MSN-based SDT with a PD-1 blockade has the potential to improve response rates and provide protection against relapse. This study provides insights into the use of azo free radicals as a promising SDT strategy for cancer treatment and establishes a basic foundation for nonoxygen-dependent SDT-triggered immunotherapy in cervical cancer treatment.

Photochemical regulation provides precise control over enzyme activities with high spatiotemporal resolution. A promising approach involves anchoring "photoswitches" at enzyme active sites to modulate substrate recognition. However, current methods often require genetic mutations and irreversible enzyme modifications for the site-specific anchoring of "photoswitches", potentially compromising the enzyme activities. Herein, we present a pioneering reversible nano-inhibitor based on molecular imprinting technique for bidirectional regulation of intracellular enzyme activity. The nano-inhibitor employs a molecularly imprinted polymer nanoparticle as its body and azobenzene-modified inhibitors ("photoswitches") as the arms. By using a target enzyme as the molecular template, the nano-inhibitor acquires oriented binding sites on its surface, resulting in a high affinity for the target enzyme and non-covalently firm anchoring of the azobenzene-modified inhibitor to the enzyme active site. Harnessing the reversible isomerization of azobenzene units upon exposure to ultraviolet and visible light, the nano-inhibitor achieves bidirectional enzyme activity regulation by precisely docking and undocking inhibitor at the active site. Notably, this innovative approach enables the facile in situ regulation of intracellular endogenous enzymes, such as carbonic anhydrase. Our results represent a practical and versatile tool for precise enzyme activity regulation in complex intracellular environments., (© 2024 Wiley-VCH GmbH.)

Azomethine imines, as a prominent class of 1,3-dipolar species, hold great significance and potential in organic and medicinal chemistry. However, the reported synthesis of centrally chiral azomethine imines relies on kinetic resolution, and the construction of axially chiral azomethine imines remains unexplored. Herein, we present the synthesis of axially chiral azomethine imines through copper- or chiral phosphoric acid catalyzed ring-closure reactions of N'-(2-alkynylbenzylidene)hydrazides, showcasing high efficiency, mild conditions, broad substrate scope, and excellent enantioselectivity. Furthermore, the biological evaluation revealed that the synthesized axially chiral azomethine imines effectively protect dorsal root ganglia (DRG) neurons by inhibiting apoptosis induced by oxaliplatin, offering a promising therapeutic approach for chemotherapy-induced peripheral neuropathy (CIPN). Remarkably, the (S)- and (R)-atropisomers displayed distinct neuroprotective activities, underscoring the significance of axial stereochemistry., (© 2023 Wiley-VCH GmbH.)

Background: Pyrazolines and azo-pyrazolines are influential groups of heterocyclic compounds with two nitrogen atoms inside the five-membered ring. They play an important role in a wide range of biological processes, such as antifungal, antioxidant, antimalarial and other antimicrobial activities., Objective: The main objective of this study is to synthesize some new heterocyclic compounds with antioxidant and antimicrobial activity Methods: One-pot three components and traditional synthesis of new azo-pyrazoline compounds were achieved in this work. The preparation process has been started by diazotizing 4-(6-methylbenzothiazol-2-yl) benzamine and its coupling reaction with 4-hydroxy acetophenone producing azo-acetophenone, followed by benzylation with benzyl chloride to form the starting material, azo-benzyloxy acetophenone. A series of substituted benzaldehydes were reacted with the latter compound via one pot and classical methods, forming new chalcones containing azo linkages and benzyloxy moieties, which were then converted into new target azo-pyrazoline derivatives., Results: The structures of the synthesized compounds were confirmed by spectroscopic techniques using FT-IR, 1 H-NMR, 13 C-NMR, and 13 C- DEPT- 135 spectra. Finally, the synthesized compounds were screened for their antioxidant and antimicrobial activities against Staphylococcus aureus and Escherichia coli ., Conclusion: Overall, the one-pot three-component synthesis of pyrazoline compounds generally provides advantages in terms of efficiency, simplicity, and time-consumption compared to classical synthesis methods. Hence, the study advocates the one-pot method because it eliminates the tedious process of making chalcones, which takes time, materials, and unnecessary effort. Therefore, this is the most convenient and effective approach to green chemistry., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Hydrazones 1-6, azo-pyrazoles 7-9 and azo-pyrimidines 10-15 are compounds that exhibit antibacterial activity. The mode of action and structures of these derivatives have been previously confirmed as antibacterial. In this investigation, biological screening and molecular docking studies were performed for derivatives 1-15, with compounds 2, 7, 8, 14 and 15 yielding the best energy scores (from -20.7986 to -10.5302 kcal/mol). Drug-likeness and in silico ADME prediction for the most potent derivatives, 2, 7, 8, 14 and 15, were predicted (from 84.46 to 96.85%). The latter compounds showed good recorded physicochemical properties and pharmacokinetics. Compound 8 demonstrated the strongest inhibition, which was similar to the positive control (eflornithine) against Trypanosoma brucei brucei (WT), with an EC 50 of 25.12 and 22.52µM, respectively. Moreover, compound 14 exhibited the best activity against Leishmania mexicana promastigotes and Leishmania major promastigotes (EC 50 =46.85; 40.78µM, respectively).

Background: Azolium salts are the organic salts used as stable precursors for generating N-Heterocyclic Carbenes and their metal complexes. Azolium salts have also been reported to have significant biological potential. Hence, in the current study, four tetra-dentate azolium salts were derived from bis-azolium salts by a new synthetic strategy., Methods: The tetra azolium salts have been synthesized by reacting the imidazole or methyl imidazole with dibromo xylene (meta, para)/ 1-bromo methyl imidazole or dibromo ethane resulting in the mono or bis azolium salts namely I-IV. V-VII have been obtained by reacting I with II-IV, resulting in the tetra azolium salts. Each product was analyzed by various analytical techniques, i.e., microanalysis, FT-IR, and NMR (1H & 13C). Salts V-VII were evaluated for their antiproliferative effect against human colon cancer cells (HCT-116) using MTT assay., Results: Four chemical shifts for acidic protons between 8.5-9.5 δ ppm in 1H NMR and resonance of respective carbons around 136-146 δ ppm in 13C NMR indicated the successful synthesis of tetra azolium salts. Salt V showed the highest IC50 value, 24.8 μM among all synthesized compounds., Conclusion: Tetra-azolium salts may play a better cytotoxicity effect compared to mono-, bi-& tri-azolium salts., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The emergence of drug-resistant viruses is a serious concern in current chemotherapy for human immunodeficiency virus type-1 (HIV-1) infectious diseases. Hence, antiviral drugs aiming at targets that are different from those of approved drugs are still required, and the RNase H activity of HIV-1 reverse transcriptase is a suitable target. In this study, a search of a series of natural compounds was performed to identify the RNase H inhibitors. Three compounds were found to block the RNase H enzymatic activity. A laccaic acid skeleton was observed in all three natural compounds. A hydroxy phenyl group is connected to an anthraquinone backbone in the skeleton. An acetamido-ethyl, amino-carboxy-ethyl, and amino-ethyl are bound to the phenyl in laccaic acids A, C, and E, respectively. Laccaic acid C showed a 50% inhibitory concentration at 8.1 μM. Laccaic acid C also showed inhibitory activity in a cell-based viral proliferation assay. Binding structures of these three laccaic acids were determined by X-ray crystallographic analysis using a recombinant protein composed of the HIV-1 RNase H domain. Two divalent metal ions were located at the catalytic center in which one carbonyl and two hydroxy groups on the anthraquinone backbone chelated two metal ions. Molecular dynamics simulations were performed to examine the stabilities of the binding structures. Laccaic acid C showed the strongest binding to the catalytic site. These findings will be helpful for the design of potent inhibitors with modification of laccaic acids to enhance the binding affinity.

The control of DNA assembly systems on cells has increasingly shown great importance for precisely targeted therapies. Here, we report a controllable DNA self-assembly system based on the regulation of G-quadruplex DNA topology by a reduction-sensitive azobenzene ligand. Specifically, three azobenzene multiamines are developed, and AzoDiTren is identified as the best G4 binder, which displays high affinity and specificity for G4 DNA. Moreover, the reduction-sensitive nature of the azobenzene scaffold allows AzoDiTren to induce a complete change of the G4 topology in a tissue-specific manner, even at high metal cation concentrations. On this basis, the AzoDiTren-induced G4 conformational switch achieves control of the self-assembly of G4-functionalized DNAs on cells. This strategy enables the regulation of G4 and DNA self-assembly by the bioreductant-responsive ligand.

The emergence of drug-resistant pathogenic microorganisms has become a public health concern, with demand for strategies to suppress their proliferation in healthcare facilities. The present study investigates the physicochemical and antimicrobial properties of carbon dots (CD-MR) derived from the methyl red azo dye. The morphological and structural analyses reveal that such carbon dots present a significant fraction of graphitic nitrogen in their structures, providing a wide emission range. Based on their low cytotoxicity against mammalian cells and tunable photoluminescence, these carbon dots are applied to bioimaging in vitro living cells. The possibility of using CD-MR to generate reactive oxygen species (ROS) is also analyzed, and a high singlet oxygen quantum efficiency is verified. Moreover, the antimicrobial activity of CD-MR is analyzed against pathogenic microorganisms Staphylococcus aureus , Candida albicans , and Cryptococcus neoformans . Kirby-Bauer susceptibility tests show that carbon dots synthesized from methyl red possess antimicrobial activity upon photoexcitation at 532 nm. The growth inhibition of C. neoformans from CD-MR photosensitization is investigated. Our results show that N-doped carbon dots synthesized from methyl red efficiently generate ROS and possess a strong antimicrobial activity against healthcare-relevant pathogens.

Studies on adverse health consequences of azo dyes are limited and conflicting. Coenzyme Q10 (CoQ10) supplementation has been shown to have benefits associated with antioxidant and anti-inflammatory characteristics on several body systems. This work investigates the possible toxic effects of the widely used food additive sunset yellow and the probable protective effects of CoQ10 on testicular tight and gap junctions in rats by assessing molecular, immunohistochemical, and histopathological changes. Sixty Sprague-Dawley male weanling rats were randomly divided into six groups (n = 10). The rats received their treatments via daily oral gavages for 6 weeks. The treatments included as follows: low dose of sunset yellow (SY-LD) (2.5 mg/kg/day), high dose of sunset yellow (SY-HD) (70 mg/kg/day), CoQ10 (10 mg/kg/day), CoQ10 with low dose of sunset yellow (CoQ10 + LD), CoQ10 with high dose of sunset yellow (CoQ10 + HD), and distilled water as the control treatment. At the end of the experiment, the rats were anesthetized, and the testes were removed for molecular (real-time quantitative PCR), immunohistochemical, and histopathological (H & E staining) assessments. Claudin 11 and occludin gene expression significantly decreased in HD and CoQ10 + HD groups compared with the controls. Connexin 43 (Cx43) expression in the control and CoQ10 groups was significantly higher than in the HD group. The immunohistochemical and histopathological data were largely in line with these findings. The results showed that exposure to a high dose of sunset yellow led to disturbances in cell-to-cell interactions and testicular function. Simultaneous treatment with CoQ10 had some beneficial effects but did not completely improve these undesirable effects., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

COVID-19 is a global health problem caused by SARS-CoV-2, which has led to over 600 million infections and 6 million deaths. Developing novel antiviral drugs is of pivotal importance to slow down the epidemic swiftly. In this study, we identified five azo compounds as effective antiviral drugs to SARS-CoV-2, and mechanism study revealed their targets for impeding viral particles' ability to bind to host receptors. Direct Blue 53, which displayed the strongest inhibitory impact, inhibited five mutant strains at micromole. In vitro, mechanism study demonstrated Direct Blue 53 inhibited viral infection through interaction with the spike of SARS-CoV-2. And 25 mg/kg/d compound treatment showed 50% or 60% survival protection against lethal Delta or Omicron BA.2 infection in vivo. Taken together, our results demonstrate that azo compounds with dimethyl-biphenyl-diyl-bis(azo)bis structure may be promising anti-SARS-CoV-2 drug candidates, which provide practicable therapies with the aid of structural optimizations and further research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Risdiplam is a daily, orally dosed, survival of motor neuron 2 (SMN2) mRNA splicing-modifying agent approved for the treatment of spinal muscular atrophy (SMA). RG7800 is a closely related SMN2 mRNA-splicing compound. Effects on secondary mRNA splice targets such as Forkhead Box M1 (FOXM1) and MAP kinase-activating death domain protein (MADD), which have been implicated in cell-cycle regulation, were observed in non-clinical studies with both risdiplam and RG7800. Potential effects of risdiplam on male fertility via FOXM1 and MADD are important as these secondary splice targets exist in humans. This publication reports the findings from 14 in vivo studies that investigated the reproductive tissues of male animals in various stages of development. Exposure to risdiplam or RG7800 induced changes within the germ cells in the testes of male cynomolgus monkeys and rats. Germ-cell changes included both cell-cycle gene changes (alteration of mRNA-splicing variants) and seminiferous tubule degeneration. In monkeys treated with RG7800, there was no evidence of damage to spermatogonia. Observed testicular changes were stage-specific with spermatocytes in the pachytene stage of meiosis and were fully reversible in monkeys following a sufficient recovery period of eight weeks following cessation of RG7800. In rats, seminiferous tubule degeneration was present, and full reversibility of germ-cell degeneration in the testes was observed among half of the rats that were exposed to risdiplam or RG7800 and then allowed to recover. With these results, coupled with histopathological findings, the effects on the male reproductive system are expected to be reversible in humans for these types of SMN2 mRNA-splicing modifiers., Competing Interests: Declaration of Competing Interests The authors declare the following which may be considered as potential competing interests: Lutz Mueller, Björn Jacobsen, and Martin Ebeling are employees and shareholders of F. Hoffmann-La Roche Ltd. At the time of the study, Paul Barrow was an employee of F. Hoffmann-La Roche Ltd and Gerhard Weinbauer was an employee of Labcorp Early Development Services., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Despite the plethora of research that exists on recombinant human bone morphogenetic protein-2 and -7 (rhBMP-2 and rhBMP-7) and has been clinically approved, there is still a need to gain information that would allow for their more rational use in bone implantology. The clinical application of supra-physiological dosages of these superactive molecules causes many serious adverse effects. At the cellular level, they play a role in osteogenesis and cellular adhesion, migration, and proliferation around the implant. Therefore, in this work, we investigated the role of the covalent binding of rhBMP-2 and rhBMP-7 separately and in combination with ultrathin multilayers composed of heparin and diazoresin in stem cells. In the first step, we optimized the protein deposition conditions via quartz crystal microbalance (QCM). Then, atomic force microscopy (AFM) and enzyme-linked immunosorbent assay (ELISA) were used to analyze protein-substrate interactions. The effect of the protein binding on the initial cell adhesion, migration, and short-term expression of osteogenesis markers was tested. In the presence of both proteins, cell flattening and adhesion became more prominent, resulting in limited motility. However, the early osteogenic marker expression significantly increased compared to the single protein systems. The presence of single proteins resulted in the elongation of cells, which promoted their migration activity.

Recent studies have shown that bacterial membrane potential is dynamic and plays signaling roles. Yet, little is still known about the mechanisms of membrane potential dynamics regulation-owing to a scarcity of appropriate research tools. Optical modulation of bacterial membrane potential could fill this gap and provide a new approach for studying and controlling bacterial physiology and electrical signaling. Here, the authors show that a membrane-targeted azobenzene (Ziapin2) can be used to photo-modulate the membrane potential in cells of the Gram-positive bacterium Bacillus subtilis. It is found that upon exposure to blue-green light (λ = 470 nm), isomerization of Ziapin2 in the bacteria membrane induces hyperpolarization of the potential. To investigate the origin of this phenomenon, ion-channel-deletion strains and ion channel blockers are examined. The authors found that in presence of the chloride channel blocker idanyloxyacetic acid-94 (IAA-94) or in absence of KtrAB potassium transporter, the hyperpolarization response is attenuated. These results reveal that the Ziapin2 isomerization can induce ion channel opening in the bacterial membrane and suggest that Ziapin2 can be used for studying and controlling bacterial electrical signaling. This new optical tool could contribute to better understand various microbial phenomena, such as biofilm electric signaling and antimicrobial resistance., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The synthetic food additive dye induces amyloid fibrillation has many implications in the laboratory and industries. The effect of Allura red (AR), on the fibrillation of ovalbumin (Ova) at pH 2.0 was investigated. The influence of salt and pH was also seen on AR-induced Ova aggregation. We have used several spectroscopic and microscopy techniques to characterize the changes. The turbidity data suggest that concentrations above 0.05 mM of AR induce aggregation, and the size of aggregates increased in response to AR concentration. The kinetics data showed that the AR induces Ova aggregation quickly without lag time. The aggregates induced by AR have amyloid-like aggregates confirmed by far-UV CD and TEM. NaCl has very marginal effects in AR-induced aggregation. The turbidity results clearly state that Ova is not forming aggregates with pH above 4.0 due to electrostatic repulsion. However, Ova forms bigger aggregates in the presence of 0.5 mM AR at a pH below 4.0. These spectroscopic data suggest that the amyloid fibrillation that occurs in Ova is due to electrostatic and hydrophobic interaction. The amyloid fibrillation induced by AR dye in protein should be taken seriously for food safety purposes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Photoresponsive inhibitor and noninhibitor systems have been developed to achieve on-demand enzyme activity control. However, inhibitors are only effective for a specific and narrow range of enzymes. Noninhibitor systems usually require mutation and modification of the enzymes, leading to irreversible loss of enzymatic activities. Inspired by biological membranes, we herein report a lipidoid-based artificial compartment composed of azobenzene (Azo) lipidoids and helper lipids, which can bidirectionally regulate the activity of the encapsulated enzymes by light. In this system, the reversible photoisomerization of Azo lipidoids triggered by UV/vis light creates a continuous rotation-inversion movement, thereby enhancing the permeability of the compartment membrane and allowing substrates to pass through. Moreover, the membrane can revert to its impermeable state when light is removed. Thus, enzyme activity can be switched on and off when encapsulating enzymes in the compartments. Importantly, since neither mutation nor modification is required, negligible loss of activity is observed for the encapsulated enzymes after repeated activation and inhibition. Furthermore, this approach provides a generic strategy for controlling multiple enzymes by forgoing the use of inhibitors and may broaden the applications of enzymes in biological mechanism research and precision medicine.

NMDA receptors play critical roles in numerous physiological and pathological processes in CNS that requires development of modulating ligands. In particular, photoswitchable compounds that selectively target NMDA receptors would be particularly useful for analysis of receptor contributions to various processes. Recently, we identified a light-dependent anti-NMDA activity of the azobenzene-containing quaternary ammonium compounds DENAQ (diethylamine-azobenzene-quaternary ammonium) and DMNAQ (dimethylamine-azobenzene-quaternary ammonium). Here, we developed a series of light-sensitive compounds based on the DENAQ structure, and studied their action on glutamate receptors in rat brain neurons using patch-clamp method. We found that the activities of the compounds and the influence of illumination strongly depended on the structural details, as even minor structural modifications greatly altered the activity and sensitivity to illumination. The compound PyrAQ (pyrrolidine-azobenzene-quaternary ammonium) was the most active and produced fast and fully reversible inhibition of NMDA receptors. The IC 50 values under ambient and monochromic light conditions were 2 and 14 μM, respectively. The anti-AMPA activity was much weaker. The action of PyrAQ did not depend on NMDA receptor activity, agonist concentration, or membrane voltage, making it a useful tool for photopharmacological studies., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The role of nitric oxide (NO) in cancer has been a continuous challenge and particularly the contradictory findings in the literature reporting NO with either anti-cancer properties or pro-cancer properties. This dilemma was largely resolved by the level of NO/inducible nitric oxide synthase in the tumor environment as well as other cancer-associated gene activations in different cancers. The initial findings on the role of NO as an anti-cancer agent was initiated in the late 1990's in Dr. Larry Keefer's laboratory, who had been studying and synthesizing many compounds with releasing NO under different conditions. Using an experimental model with selected NO compounds they demonstrated for the first time that NO can inhibit tumor cell proliferation and sensitizes drug-resistant cancer cells to chemotherapy-induced cytotoxicity. This initial finding was the backbone and the foundation of subsequent reports by the Keefer's laboratory and followed by many others to date on NO-mediated anti-cancer activities and the clinical translation of NO donors in cancer therapy. Our laboratory initiated studies on NO-mediated anti-cancer therapy and chemo-immuno-sensitization following Keefer's findings and used one of his synthesized NO donors, namely, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETANONOate), throughout most of our studies. Many of Keefer's collaborators and other investigators have reported on the selected compound, O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl] diazen-1-ium-1,2-diolate (JS-K), and its therapeutic role in many tumor model systems. Several lines of evidence that investigated the treatment with NO donors in various cancer models revealed that a large number of gene products are modulated by NO, thus emphasizing the pleiotropic effects of NO on cancers and the identification of many targets of therapeutic significance. The present review reports historically of several examples reported in the literature that emanated on NO-mediated anti-cancer activities by the Keefer's laboratory and his collaborators and other investigators including my laboratory at the University of California at Los Angeles.

Background: Textile materials are susceptible to microbial attack as they provide suitable conditions for their growth. The microbes grow with normal body secretions on garments. These microbes are responsible for the weakening, brittleness, and discoloration of the substrate. Furthermore, they cause many health issues to the wearer, including dermal infection, bad odour etc. They threaten the human health as well as create tenderness in fabric., Objectives: Usually, antimicrobial textiles are prepared by applying antimicrobial finishes after dyeing, which is an expensive approach. Concerning these adversities, in the present study, a series of antimicrobial acid-azo dyes have been synthesized by incorporating antimicrobial sulphonamide moiety into the dye molecules during its synthesis., Methods: A commercially available sulphonamide-based compound, sulfadimidine Na-salt was used as a diazonium component and coupled with different aromatic amines to get desired dye molecules. Since dyeing and finishing are two separate energy-intensive processes, in the current research work, an approach to combine both processes in one step has been adopted that would be economical, timesaving, and environment friendly. Structures of the resultant dye molecules have been confirmed using different spectral techniques such as Mass spectrometry, 1 H-NMR spectroscopy, FT-IR, and UV-Visible spectroscopy., Results: Thermal stability of the synthesized dyes was also determined. These dyes have been applied to wool and nylon-6 fabrics. Their various fastness properties were examined using ISO standard methods., Conclusion: All the compounds exhibited good to excellent fastness properties. The synthesized dyes and the dyed fabrics were screened biologically against Staphylococcus aureus ATCC 6538 and Escherichia coli ATCC 10536, resulting in significant antibacterial activities., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aryl hydrocarbon receptor (AhR) antagonism is known to expand human hematopoietic stem cells (HSCs). However, its regulatory effect on the lineage-skewed differentiation of HSCs has not been sufficiently studied. Here, we investigate the effect of the AhR-selective antagonist CH223191 on the regulation of HSC differentiation. Consistent with the well-known effects of AhR antagonists, CH223191 treatment increase phenotypic HSCs (Lin-CD34 + CD38-CD90 + CD45RA-) and preserves their functionality. On the other hand, CH223191 leads to an overall expansion of megakaryocyte (MK)-lineage populations, such as MK progenitors (MKps, CD34 + CD41 +), immature MKs (CD41 + CD42b-), and mature MKs (CD41 + CD42b +), and it also activates MK/platelet-associated signaling pathways. Furthermore, CH223191 expands MKps, mature MKs, and p-selectin (CD62p)-positive platelet-like particles in immune thrombocytopenia (ITP) patient bone marrow (BM). These results highlight the numerical expansion of human MK-lineage progeny through AhR antagonism with CH223191. This approach using CH2231291 may be applicable in the development of auxiliary treatment regimens for patients with abnormal thrombopoiesis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Protein-ligand (GOLD) docking of the NCI compounds into the ligand-binding site of Plasmodium falciparum adenosine deaminase (PfADA) identified three most active azo compounds containing 4-[(4-hydroxy-2-oxo-1H-quinolin-3-yl) moiety. These compounds showed IC 50 of 3.7-15.4 μM against PfADA, as well as inhibited the growth of P. falciparum strains 3D7 (chloroquine (CQ)-sensitive) and K1 (CQ-resistant) with IC 50 of 1.8-3.1 and 1.7-3.6 μM, respectively. The identified compounds have structures similar to the backbone structure (4-N-(7-chloroquinolin-4-yl)) in CQ, and NSC45545 could mimic CQ by inhibiting the bioformation of hemozoin in parasitic food vacuole. The amount of in situ hemozoin in the ring-stage parasite was determined using a combination of synchrotron transmission Fourier transform infrared microspectroscopy and Principal Component Analysis. Stretching of the C-O bond of hemozoin propionate group measured at 1220-1210 cm -1 in untreated intraerythrocytic P. falciparum strains 3D7 and K1 was disappeared following treatment with 1.85 and 1.74 μM NSC45545, similar to those treated with 0.02 and 0.13 μM CQ, respectively. These findings indicate a novel dual function of 4-[(4-hydroxy-2-oxo-1H-quinolin-3-yl) azo compounds in inhibiting both PfADA and in situ hemozoin biocrystallization. These lead compounds hold promise for further development of new antimalarial therapeutics that could delay the onset of parasitic drug resistance., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Dihydromaniwamycin E ( 1 ), a new maniwamycin derivative featuring an azoxy moiety, has been isolated from the culture extract of thermotolerant Streptomyces sp. JA74 along with the known analogue maniwamycin E ( 2 ). Compound 1 is produced only by cultivation of strain JA74 at 45 °C, and this type of compound has been previously designated a "heat shock metabolite (HSM)" by our research group. Compound 2 is detected as a production-enhanced metabolite at high temperature. Structures of 1 and 2 are elucidated by NMR and MS spectroscopic analyses. The absolute structure of 1 is determined after the total synthesis of four stereoisomers. Though the absolute structure of 2 has been proposed to be the same as the structure of maniwamycin D, the NMR and the optical rotation value of 2 are in agreement with those of maniwamycin E. Therefore, this study proposes a structural revision of maniwamycins D and E. Compounds 1 and 2 show inhibitory activity against the influenza (H1N1) virus infection of MDCK cells, demonstrating IC 50 values of 25.7 and 63.2 μM, respectively. Notably, 1 and 2 display antiviral activity against SARS-CoV-2, the causative agent of COVID-19, when used to infect 293TA and VeroE6T cells, with 1 and 2 showing IC 50 values (for infection of 293TA cells) of 19.7 and 9.7 μM, respectively. The two compounds do not exhibit cytotoxicity in these cell lines at those IC 50 concentrations.

Light has been used increasingly as an external stimulus in drug design. Herein, we report a novel photoswitchable azo-PI3K inhibitor, which bears an azobenzene moiety and can be efficiently converted between trans and cis configuration with changes of anticancer activity upon different light irradiation. Its photochemical properties were characterized by UV, LC-MS and NMR techniques. In biological assessment, trans and cis isomers of the azo-PI3K inhibitor exhibited differential anticancer activity in inhibition of PI3K pathway, cell migratory ability, and colony formation and can be switched at a cellular level upon light irradiation. Moreover, both isomers of the azo-PI3K inhibitor significantly inhibited tumor growth in a zebrafish xenograft model. Together, this photoswitchable azo-PI3K inhibitor may be useful as a valuable tool compound for studying the PI3K pathway and further optimization toward optically-controlled anticancer activity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Novel photoswitches offering features complementary to the well-established azobenzenes are increasingly driving high-precision research in cellular photopharmacology. Styrylthiazolium (StyTz) and styrylbenzothiazolium (StyBtz) are cellularly untested E / Z -isomerisation photoswitches which are nearly isosteric to azobenzenes, but have distinct properties: including ca. 60 nm red-shifted π → π* absorption, self-reporting fluorescence, Z → E relaxation on typical biological timescales, and decent solubility (positive charge). We tested StyTz and StyBtz for their potential as photopharmaceutical scaffolds, by applying them to photocontrol microtubule dynamics. They light-specifically disrupt microtubule network architecture and block cell proliferation: yet, testing lead compound StyBtz2 for its molecular mechanism of action showed that it did not inhibit microtubule dynamics. Using its self-reporting fluorescence, we tracked its localisation in live cells and observed accumulation of E -StyBtz2 into mitochondria; during prolonged illumination, it was released into the cytosol, and blebbing and cell death were observed. We interpret this as light-dependent rupturing of mitochondria on acute timescales. We conclude that StyTz/StyBtz can be interesting photopharmaceutical scaffolds for addressing mitochondrial, rather than cytosolic, targets.

Azo molecules, characterized by the presence of a -N=N- double bond, are widely used in various fields due to their sensitivity to external stimuli, ch as light. The emergence of bacterial resistance has pushed research towards designing new antimicrobial molecules that are more efficient than those currently in use. Many authors have attempted to exploit the antimicrobial activity of azobenzene and to utilize their photoisomerization for selective control of the bioactivities of antimicrobial molecules, which is necessary for antibacterial therapy. This review will provide a systematic and consequential approach to coupling azobenzene moiety with active antimicrobial molecules and drugs, including small and large organic molecules, such as peptides. A selection of significant cutting-edge articles collected in recent years has been discussed, based on the structural pattern and antimicrobial performance, focusing especially on the photoactivity of azobenzene and the design of smart materials as the most targeted and desirable application., Competing Interests: The authors declare no conflict of interest.