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The photophysical properties of tris(polypyridyl)ruthenium(II) complex [Ru(dmbpy)3]2+ [dmbpy = 4,4′-dimethyl-2,2′-bipyridine] were investigated and compared with [Ru(bpy)3]2+ following both experimental and computational approaches. The variations in the electronic properties of the complex in the ground and excited states were determined by density functional theory (DFT) methods, and their effects on the anticancer, antioxidant, and antimicrobial activities were also evaluated by molecular docking and dynamic simulation studies. The potential of these complexes to serve as bioanalytes was investigated by their ability to bind with quinones, the well-known electron mediators in numerous light-driven reactions. Following the above, the anticancer properties were evaluated against breast cancer-related proteins. The results revealed that the complex possesses comparable anticancer and antioxidant potential to that of [Ru(bpy)3]2+. The physical, electronic, and biological properties of this complex depend on the nature of the ligands and the medium of investigation. Herein, the potential applications of [Ru(bpy)3]2+ in clinical diagnostics as antioxidants and therapeutic agents were evaluated. [ABSTRACT FROM AUTHOR]

Series of indole‐1,3,4‐thiadiazole compounds (IT 1–7) were synthesized and characterized by FT‐IR, 1H NMR, 13C NMR and ESI‐MS spectral data. Further, the compounds (IT 1–7) were screened for antidiabetic, antioxidant and anti‐inflammatory activities. Most of these compounds exhibited moderate to good antidiabetic, antioxidant and anti‐inflammatory activities against α‐amylase enzyme, ABTS and lipoxygenase enzyme, respectively. Among these, IT‐1 displayed the better activity compared to that of standard drugs. The mechanism of binding of IT‐1, IT‐5 and IT‐6 with a transporter protein, human serum albumin was investigated by fluorescence spectroscopic and circular dichroism studies. These compounds quenched the intrinsic fluorescence intensity of HSA and moderate binding was evident from the values of binding constants which are in the order of 105 M−1. The molecular docking studies of the compounds were performed against human pancreatic alpha‐amylase in complex with montbretin A (PDB ID: 4W93). The studied compounds interacted with amino acid residues (ASP197, GLU240 and TYR151) which were similar to that of the reference drug, acarbose. The ADME properties of designed compounds were studied using SwissADME software. All the compounds obeyed Lipinski's rule of five. All the compounds showed low or non‐toxicity towards different toxicity classes as analyzed using ProTox‐II online tool. [ABSTRACT FROM AUTHOR]

The binding studies of DNA with small molecules have been an emerging field of research all the time since DNA as the genetic material is a major biological target for various drugs. Interpretation of small molecule-DNA binding helps in understanding their interactions with designing new drugs of greater medicinal activity. Posaconazole is an antifungal drug in the class of triazoles which are known to possess numerous pharmacological properties. In this work, the nature of the binding of posaconazole with calf-thymus DNA has been studied using spectroscopic techniques and molecular docking studies. A binding constant of the order of 103 M−1 was observed from UV–visible and fluorescence studies for the interaction between posaconazole and calf-thymus DNA. The fluorescence property of posaconazole was found to be quenched by calf-thymus DNA with a quenching constant of the order of 103 M−1. Competitive displacement of ethidium bromide and Hoechst 33258 by posaconazole using fluorescence technique suggested minor groove binding of posaconazole in calf-thymus DNA. Confirmation of the binding mode was further complemented by the viscosity measurement and DNA melting studies followed by KI quenching experiments. The studies on the effect of ionic strength on the binding suggested a possible role of electrostatic force in the interaction. Molecular docking studies reflected a crescent shape of the posaconazole within the minor groove of calf-thymus DNA validating the experimental findings showing the residues involved in the interaction. [ABSTRACT FROM AUTHOR]

[Display omitted] • 1,3,4-oxadiazole-thiazolidine-2,4-dione hybrid compounds (TOT-1 to 15) were synthesized, characterized and screened for various biological activities. • Single-crystal X-ray diffraction data was collected for the intermediate compound, TOT and its structure was proposed. • The compounds, TOT 12–15 exhibited significant anti-cancer activity. • Molecular docking studies were carried out. Two synthetic methods were proposed for the preparation of a new series of thiophene-1,3,4-oxadiazole-thiazolidine-2,4-dione hybrids (TOT-1 to 15) and their structures were elucidated based on spectral data. Studies on cytotoxicity, ROS, cellular uptake and interactions of TOT-14 with calf thymus DNA were carried out. Anticancer activity of compounds, TOT-1 to 15 on breast cancer (MCF-7) cell lines was investigated. The IC 50 values for the standard, epirubicin hydrochloride and TOT-12, 13, 14 and 15 were found to be 6.78, 5.52, 6.53, 4.83 and 5.57 µg/mL, respectively. Notably, TOT-14 exhibited a remarkable antiproliferative activity with a strikingly selective inhibitory effect compared to standard. This specific selectivity could be attributed to the synergistic effect of increased cellular uptake and generation of higher ROS in cancer cells after irradiation. The binding constant of 4.25 x 103 M−1 indicated the moderate interaction between TOT-14 and ct-DNA. The docking score of TOT derivatives was substantially identical to the docking score of epirubicin hydrochloride. The designed molecules complied with the requirements for drug-likeness and ADME. [ABSTRACT FROM AUTHOR]

In this study we report the in vitro activities of four cyclic opioid peptides with various sequence length/macrocycle size and N -methylamino acid residue content. N -Methylated amino acids were incorporated and cyclization was employed to enhance conformational rigidity to various extent. The effect of such modifications on ligand structure and binding properties were studied. The pentapeptide containing one endocyclic and one exocyclic N -methylated amino acid displayed the highest affinity to the mu-opioid receptor. This peptide was also shown to be a full agonist, while the other analogs failed to activate the mu opioid receptor. Results of molecular docking studies provided rationale for the explanation of binding properties on a structural basis. [ABSTRACT FROM AUTHOR]

The physicochemical properties of polybrominated diphenyl ethers are important for modeling their transport, but these data are often missing. Here, satisfactory bioactivity results were obtained using human serum albumin as the carrier, 2,2′,4,4′,5,6′-hexabromodiphenyl ether (BDE154) and 3-hydroxy-2,2′,4,4′, 5,6′-hexabromodiphenyl ether (3OH-BDE154) as the ligands, using UV–visible absorbance, fluorescence, circular dichroism, molecular docking, and molecular dynamics methods. The interactions between human serum albumin and BDE154 or 3OH-BDE154 were verified, consistent with the static quenching procedure. At pH 7.4, the binding constants of the complexes for site I were relatively comparable and increased in the order BDE154 < 3OH-BDE154. Then, the secondary structure and kinetic parameters of albumin were analyzed using the circular dichroism spectra and GROMACS software. The data obtained from these simulations indicate that hydrophobic attraction might be the key factor for the stability of complexes. The docking experiments provided further insight into the hydrophobic pocket and showed that 3OH-BDE154 has a stronger binding affinity to human serum albumin than BDE154. The experimental spectral data were obtained and compared with the simulation results, showing good agreement. A detailed analysis of PBDEs–HSA interactions would provide valuable information to better understand the interaction on this class of compounds. [ABSTRACT FROM AUTHOR]

Morphiceptin (Tyr-Pro-Phe-Pro-NH 2 ), a tetrapeptide amide, is a selective ligand of the μ-opioid receptor (MOR). This study reports the synthesis and biological evaluation of a series of novel morphiceptin analogs modified in positions 2 or/and 4 by introduction of 4,4-difluoroproline (F 2 Pro) in l or d configuration. Depending on the fluorinated amino acid configuration and its position in the sequence, new analogs behaved as selective full MOR agonists showing high, moderate, or relatively low potency. The most potent analog, Tyr-F 2 Pro-Phe- d -F 2 Pro-NH 2 , was also able to activate the κ-opioid receptor (KOR), although with low potency. Docking studies and the comparison of results with the high resolution crystallographic structure of a MOR-agonist complex revealed possible structure–activity relationships of this compound family. [ABSTRACT FROM AUTHOR]

• The synthesized compounds displayed potent in vitro antidiabetic activity. • The single-crystal X-ray investigation validated the molecular structure. • The interaction of compounds with HSA has been studied. • Molecular docking studies were carried out. 2,4-thiazolidinedione-phenothiazine molecular hybrids, 9a–9t were synthesized, characterized and screened for antidiabetic activities viz., α -amylase inhibition and glucose uptake assay. The synthesized compounds were characterized by spectroscopic techniques. The molecule 9p was grown into single crystals, and its crystal structure and refinement data were deliberated. Most of the compounds displayed a significant to moderate α-amylase inhibition and glucose uptake activity. The compounds, 9m-9p showed a significant α-amylase inhibition with IC 50 values (83.7 ± 0.7 - 60.8 ± 0.8 µM), which are greater than that of the standard, acarbose (101.7 ± 2.0 µM). Most of the compounds showed good glucose uptake assay and compounds, 9a- 9 g showed IC 50 values in the range of 169.8 ± 1.2 - 213.3 ± 0.5 µM which are ∼2-fold greater compared to that of the standard, metronidazole (441.5 ± 2.1 µM). The compound, 9l showed acceptable values for both α-amylase inhibition (IC 50 = 130.6 ± 2.0 µM) and glucose uptake assay (IC 50 = 459.3 ± 2.2 µM) compared to those of the standard. Molecular docking studies confirmed interactions of the compounds with the human pancreatic α-amylase protein with PDB ID: 2QV4. Further, the interactions of 9o and 9p with human serum albumin were also investigated. [Display omitted] [ABSTRACT FROM AUTHOR]

Cyclic pentapeptide Tyr-c[D-Lys-Phe-Phe-Asp]NH 2, based on the structure of endomorphin-2 (EM-2), which shows high affinity to the μ-opioid receptor (MOR) and a very strong antinociceptive activity in mice was used as a parent compound for the structure–activity relationship studies. In this report we synthesized analogs of a general sequence Dmt-c[D-Lys-Xaa-Yaa-Asp]NH 2 , with D-1- or D-2-naphthyl-3-alanine (D-1-Nal or D-2-Nal) in positions 3 or 4. In our earlier papers we have indicated that replacing a phenylalanine residue by the more extended aromatic system of naphthylalanines may result in increased bioactivities of linear analogs. The data obtained here showed that only cyclopeptides modified in position 4 retained the sub-nanomolar MOR and nanomolar κ-opioid receptor (KOR) affinity, similar but not better than that of a parent cyclopeptide. In the in vivo mouse hot-plate test, the most potent analog, Dmt-c[D-Lys-Phe-D-1-Nal-Asp]NH 2 , exhibited higher than EM-2 but slightly lower than the cyclic parent peptide antinociceptive activity after peripheral (ip) and also central administration (icv). Conformational analyses in a biomimetic environment and molecular docking studies disclosed the structural determinants responsible for the different pharmacological profiles of position 3- versus position 4-modified analogs. [ABSTRACT FROM AUTHOR]

• Three characteristic phenylethanol glycosides (PhGs) were selected to investigate the cytotoxicity on hela cells. • The binding mechanism of three phgs with human serum albumin (HSA) were elaborated by spectroscopic, microscopic, and simulative technologies. • A rare fluorescence increase behavior was observed when phgs 3 was added into HSA solution. Phenylethanol glycosides (PhGs) possessing various biological activities and good safety, are a large group of natural compounds extensively distributed in plant species. However, the interaction of PhGs with human serum albumin (HSA) is not reported, which is of guiding significance to expound the absorption and metabolism mechanism of PhGs in vivo. In this work, three natural PhGs containing biogenetic relationships, namely acteoside, cistanoside F, and decaffeoylacteoside were selected to investigate the cytotoxicity activity on human cervical cancer cell line (HeLa). Further, the binding affinity and mechanism of three PhGs with HSA were comprehensively elaborated by fluorescence spectroscopy, nuclear magnetic resonance, circular dichroism, atomic force microscopy and molecular docking. The results displayed that three PhGs inhibited the HeLa cells growth in a concentration-dependent manner with the IC 50 values of 22.84, 78.20 and 47.86 μM, respectively. Fluorescence spectra demonstrated the fluorescence strength of HSA was obviously quenched by acteoside and cistanoside F, while amazingly the fluorescence strength of HSA was enhanced by decaffeoylacteoside. Spectroscopic technologies demonstrated three PhGs can be bound to HSA with the higher affinity (the binding constant K a of PhGs 1, 2 and 3 was 1.23, 1.14 and 0.65 × 105, respectively) mainly through hydrophobic forces and hydrogen bonds, and the secondary configuration of HSA after treating with the PhGs was also mainly α -helix. Microscopic technology exhibited that HSA became more expanded and dispersed when combined with the PhGs. Molecular docking presented the molecular recognition pattern and evaluated the stability of the binary system between the PhGs and HSA. [Display omitted] [ABSTRACT FROM AUTHOR]

• Ascorbic acid or vitamin C is an antioxidant prescribed in flu infections (COVID). • Colchicine is used to treat gouty arthritis Ascorbic acid or. • Plasma protein binding plays significant role in pharmacokinetics of drugs. • Colchicine and vitamin C can displace each other from plasma protein binding site. • Effect of vitamin C was investigated on colchicine-BSA interaction. Two or more drugs are prescribed commonly to patients depending on their physical health conditions. Concomitant drugs might lead to specific drug-drug interactions with serum albumin, the main transporter protein present in the blood. This study evaluated the effect of colchicine on the binding of ascorbic acid (vitamin C) commonly prescribed in viral infections to bovine serum albumin (BSA). The interaction was evaluated using fluorescence spectroscopy, absorption spectroscopy, molecular docking, and molecular dynamic simulation. A static quenching mechanism was observed for both BSA-colchicine and BSA-ascorbic interaction. The binding constant for the BSA-ascorbic acid system decreased from 1.23 × 105 to 0.26 × 102 in the presence of colchicine, whereas the binding constant of BSA-colchicine decreased from 1.39 × 105 to 4.81 × 102 in the presence of ascorbic acid. Thus, the binding of ascorbic acid and colchicine was significantly affected in the presence of each other. Co-administration of colchicine and ascorbic acid needs to be studied further as the co-administration may lead to serious adverse events in patients taking vitamin C supplements and under treatment with colchicine. [ABSTRACT FROM AUTHOR]

Tobacco mosaic virus helicase (TMV-Hel) plays important roles in viral multiplication. TMV-Hel is a potential target of anti-TMV agents. Our previous studies expressed and purified TMV-Hel as target protein for cytosinpeptidemycin. In this study, we preform molecular docking to study the binding sites of commercial antiviral agents with TMV-Hel. Then we verify the interactions between the potential anti-TMV agents and TMV-Hel in vitro using Microscale Thermophoresis experiment and study the inhibiting expression of TMV-Hel with the potential anti-TMV agents in vivo using Western-blot (WB) method. The results showed that ribavirin bound to TMV-Hel with a dissociation constant of 1.55 μM by direct interaction with eight binding sites, which was consistent with the docking studies. Ribavirin inhibited the expression of TMV-Hel in Nicotiana benthamiana. Docking studies combined Microscale Thermophoresis and WB experiment provided a new method to screen anti-TMV agents targeting TMV-Hel. Diseases of crops caused by tobacco mosaic virus (TMV) are severe threat to both the quality and yield of these agricultural products globally, and they are proven extremely difficult, if not possible to control. Studies aiming at controlling TMV have been focusing on hunting for disease resistance proteins. Viral helicase proteins, on the other hand, have been rarely targeted for the development of antiviral compounds. In this study, by using both in vitro and in vivo assay developed for the effects of compounds on TMV helicase, we found that ribavirin, was able to binding directly to TMV-Hel and inhibited the expression of TMV-Hel in Nicotiana benthamiana. In vitro combined and in vivo experiment provided a new method to screen anti-TMV agents targeting TMV-Hel. Unlabelled Image • Ribavirin bound to TMV-Hel protein with a dissociation constant of 1.55 μM. • Ribavirin direct interacts with TMV-Hel via hydrogen bonding. • Ribavirin inhibited the expression of TMV-Hel in Nicotiana benthamiana. • A new method to screen Anti-TMV agents targeting TMV-Hel. [ABSTRACT FROM AUTHOR]