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The single-stranded RNA genome of SARS-CoV-2 encodes several structural and non-structural proteins, among which the papain-like protease (PLpro) is crucial for viral replication and immune evasion and has emerged as a promising therapeutic target. The current study aims to discover new inhibitors of PLpro that can simultaneously disrupt its protease and deubiquitinase activities. Using multiple computational approaches, six compounds (CP1-CP6) were selected from our in-house compounds database, with higher docking scores (−7.97 kcal/mol to −8.14 kcal/mol) and fitted well in the active pocket of PLpro. Furthermore, utilizing microscale molecular dynamics simulations (MD), the dynamic behavior of selected compounds was studied. Those molecules strongly binds at the PLpro active site and forms stable complexes. The dynamic motions suggest that the binding of CP1 - CP6 brought the protein to a closed conformational state, thereby altering its normal function. In an in vitro evaluation, CP2 showed the most significant inhibitory potential for PLpro (protease activity = 2.71 ± 0.33 μM and deubiquitinase activity = 3.11 ± 0.75 μM), followed by CP1 , CP5 , CP4 and CP6. Additionally, CP1 - CP6 showed no cytotoxicity at a concentration of 30 μM in the human BJ cell line. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat pain, fever, and inflammation. In this paper, we report four new alkali metal complexes (1–4) containing 1,10-phenanthroline (phen), and two NASID drugs, that is, ibuprofen (ibu) and flurbiprofen (fibu). Complexes 1–4 were characterized by a variety of analytical techniques including infrared and UV-vis spectroscopy, 1H NMR, and single-crystal and powder X-ray diffraction analysis. In complexes 1–4, phen binds via an N,N′-chelate pocket, while the ibu and fibu ligands coordinate in a bidentate fashion in all four complexes. The complexes were evaluated for their anticancer activity against lung and oral cancer cell lines. The complexes displayed excellent activities against oral and lung cancer cells with the least toxicity toward normal cells when compared to the standard drug 5-fluorouracil. [ABSTRACT FROM AUTHOR]

The coordination chemistry of 1,10‐phenanthroline (phen) and sodium 1,3‐benzothiazole‐2‐thiolate (SBT) with selected s‐block elements has been investigated. Four metal complexes were prepared and their structures were characterized using a variety of analytical techniques including infrared, UV–visible, 1H NMR and 13C NMR spectroscopies, elemental analysis, mass spectrometry and single‐crystal X‐ray diffraction. The reactions of phen and SBT with M(X)n (M = K(I), Cs(I), Mg(II), Sr(II); X = OH−, CO3−, Cl−; n = 1, 2) in MeOH–H2O yielded one‐dimensional chains of both potassium [K2(phen)2(BT)2(H2O)4]n (1) and caesium [Cs(phen)(BS)(H2O)]n (2) (where BT = 1,3‐benzthiazole‐2‐thiolate and BS = 1,3‐benzthiazole‐2‐sulfinothiolate) and mononuclear complexes of both magnesium {[Mg(phen)(H2O)4](BT)2·phen} (3) and strontium {[Sr(phen)2(H2O)4](BT)2} (4). In these complexes, phen binds via an N,N′ chelate pocket, while the monoanonic BT− ligands either coordinate in a bidentate fashion (in the case of 1) or remain uncoordinated (in the case of 3 and 4). In complex 2, SBT ligand was oxidized in situ into a new BS ligand. The sulfinothiolate oxygen atoms in BS coordinate with caesium in a tridentate fashion. Complexes 1–4 were evaluated against urease for enzyme inhibition. The complexes displayed significant inhibition with IC50 values in the range 10.8–45.8 μM. In order to examine the structure–activity relationship, the complexes were docked at the active site of urease. Docking results clearly demonstrate the binding of each complex within the active site of the enzyme. [ABSTRACT FROM AUTHOR]

Pyranone natural products have attracted great attention in recent years from chemists and biologists due to their fascinating stereoisomeric structural features and impressive bioactivities. A large number of stereoselective total syntheses of these compounds have been described in the literature. The natural pyranones with long side chains have recently received significant importance in the synthetic field. In the present article, we aim to review the modern progress of the stereoselective total syntheses of these natural pyranones containing long-chain substituents. [ABSTRACT FROM AUTHOR]

Squaramide–quaternary ammonium salt is illustrated as a simple, tunable, and competent metal‐free binary catalytic platform for the atom‐economic conversion of epoxides and isocyanates into oxazolidinones. Although, various metal catalysts have been employed for the title reaction, application of organocatalysis is scarce. At first, a rational survey of catalytic activity of several air‐stable and architecturally distinct squaramides was undertaken. Thereafter, the impact on catalytic capability of different parameters, such as temperature, catalyst loading, and nature of nucleophiles, was examined. This binary organocatalytic system for the oxazolidinone synthesis, composed of a squaramide entity along with a suitable halide anion, was applied to the challenging conversion of a plethora of alkyl‐ and aryl‐substituted epoxides– including disubstituted and enantioenriched ones– and isocyanates into the corresponding oxazolidinones in high‐to‐excellent yields. The time‐dependent formation of oxazolidinone from epoxide and isocyanate was monitored by FTIR‐ATR and 1H NMR spectroscopy and the scalability of this process was also described. In light of 1H NMR experiment, a hydrogen‐bonding/anion‐binding mechanism was proposed wherein the nucleophilic ring‐opening operation, and oxo‐ and carbamate‐anions stabilization occur cooperatively towards isocyanate fixation. [ABSTRACT FROM AUTHOR]

In the current investigation, 5- epi -incensole (3) and 5- epi -incensole acetate (5) were synthesized from the most potent anti-depressant constituents incensole (1) and incensole acetate (2) of Boswellia papyrifera Hochst. The resulting compounds were evaluated for their ability to ameliorate depressive symptoms in forced swim test (FST) and tail suspension test (TST) in chronic unpredictable mild stress (CUMS) induced depression paradigm. The results demonstrated that compounds 3 and 5 at the doses of 1 and 3 mg/kg administered for 28 days, significantly reduced the immobility time in FST and TST and were devoid of any effect on locomotor activity in the open field test (OFT). Both compounds 3 and 5 also reversed CUMS-induced reduction in the weight of animals and aversion in sucrose preference. The tested compounds also inhibited Monoamine oxidase-A (MAO) enzyme and increased the levels of brain noradrenaline (NA) and 5-Hydroxytryptamine (5-HT), decreased plasma corticosterone and pro-inflammatory cytokines including TNF-α, IL-6 in hippocampal homogenates. Compounds 3 and 5 also significantly reduced the increased lipid peroxidation and nitrite levels; decreased glutathione levels, and catalase activities in mice undergoing CUMS protocol. The binding mode of compounds 3 and 5 was predicted at the monoamine oxidase substrate binding site by molecular docking having docking scores of > −6 kcal/mol. Taken together these data revealed that compounds 3 and 5 exerted antidepressant-like effects in chronic unpredictable mild stress-induced depression paradigm and are likely mediated via modulating the central oxidative stress, MAO-A activity with a consequent increase in brain NA and 5-HT levels in inflammatory pathways. • 5-epi-incensole (3) and 5-epi-incensole acetate (5) were synthesized from potent anti-depressant constituents incensole (1) and incensole acetate (2) of Boswellia papyrifera. • Both compounds 3 and 5 were evaluated in forced swim test and tail suspension test in chronic unpredictable mild stress. • These compounds also inhibited Monoamine oxidase-A (MAO) and decreased the levels of plasma corticosterone and pro-inflammatory cytokines including TNF-α, IL-6 in hippocampal homogenates. • Compounds 3 and 5 also significantly reduced lipid peroxidation and nitrite levels, decreased glutathione levels and catalase [ABSTRACT FROM AUTHOR]

[Display omitted] • Different derivatives of incensole (1) and incensole acetate (2) were synthesized in the present study. • The structures of synthesized compounds were confirmed using advance spectroscopic techniques NMR and Mass Spectrometry. • Compounds 3a - e and 4a - c were investigated for their putative anti-depression activities using classical mouse models of depression of FST and TST. • The results determined that compounds 3a-e caused dose dependent reduction in immobility time compared to the vehicle control, with 4c-4e demonstrating higher potency and efficacy. • Similar results were obtained with compounds 4a-c , with 4b and 4c found to be the most potent and efficacious among the studied compounds. • Furthermore, molecular docking has predicted that compounds 3e and 4c bind at the GABA binding site of GABA A receptor in order to produce GABAergic effects. Encouraged by the potent anti-depression activities of incensole (1) and incensole acetate (2) isolated from the resin of Boswellia papyrifera in our previous work, different derivatives of 1 and 2 were synthesized in the present study. The reaction of 1 with m -CPBA afforded the mono-epoxide derivative 3a , while the same reaction with 2 led to three different epoxide derivatives 3a , 3b , and 3c. Oxidation of 1 with PCC to get compound 3b , however along with the target 3b, the reaction gave three interesting side products (3c-3e). Oxime (3b-1) resulted from the reaction of 3b with hydroxylamine hydrochloride in pyridine, while epoxidation of 2 generate three epoxide products (4a-4c). The structures of all products were unambiguously confirmed using NMR and Mass spectrometry. Compounds 3a - e and 4a - c (0.1–3 mg/kg, i.p.) demonstrated promising anti-depression activities in classical mouse models of depression of FST and TST. The results showed that compounds 3a-e and 4a-c (0.1–3 mg/kg, i.p.) caused dose dependent reduction in immobility time compared to the vehicle control, with 3c-3e and 4b-4c demonstrating higher potency and efficacy. The findings of the open field test excluded the motor effects of these compounds, thus further confirming their anti-depression activity. Preliminary investigation into their mechanism of action using GABA antagonist, PTZ and molecular docking has predicted that compounds 3e and 4c bind at the GABA binding site of GABA A receptor to produce GABAergic effects. Furthermore, the promising anti-depression potency of compounds 1 and 2 and their derivatives make them lead compounds for drug discovery. [ABSTRACT FROM AUTHOR]

β -Boswellic acid (β -BA) and 11-keto- β -boswellic acid (β -KBA) are crucial bioactive compounds, mostly isolated from frankincense. These compounds are known for their potent anticancer and anti-inflammatory activities. Herein, we have explored the complete anti-diabetic potential of β -BA and β -KBA with detailed parameters. This research revealed that treatment with β -BA and β -KBA at a dose of 1, 2, and 10 mg/kg body weight for 21 days significantly improved body weight loss, water consumption, and specifically the concentration of blood glucose level (BGL) in diabetic animals, which indicated that the β -BA and β -KBA possess strong anti-diabetic activities. Serum total superoxide dismutase (SOD) and malondialdehyde (MDA) assays were also performed to evaluate the antioxidant effects. The biochemical analysis revealed that these compounds improve an abnormal level of several biochemical parameters like serum lipid values including total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C) to a normal level and the high-density lipoprotein cholesterol level (HDL-C). To understand the mechanism of action of β -BA and β -KBA, their most probable biological targets were searched through the inverse docking approach. Our computational analysis reflects that among other probable targets, the Dipeptidyl peptidase 4 (DPP-4) enzyme could be one of the possible binders of β -BA and β -KBA to produce their anti-diabetic activities. These in-silico results were validated by an in-vitro experiment. It indicates that the anti-diabetic effects of β -BA and β -KBA are produced by the inhibition of DDP-4. Thus, these anti-diabetic, antioxidant, and anti-hyperlipidemic effects of β -BA and β -KBA suggest these compounds as potential therapeutics for diabetic conditions. [Display omitted] • β -BA and β -KBA were isolated from oleo-gum resins of B. sacra. • In-vivo antidiabetic potential of β -BA and β -KBA was evaluated in STZ-induced high-fat diet diabetes mellitus. • β -BA and β -KBA reduced the hyperglycemia condition and improved biochemical parameters like lipid profile. • Both compounds possess in-vitro antioxidant potential. • DPP-4 was identified as prominent target for β -BA and β -KBA by in-silico target fishing. • In-silico results were validated by in-vitro assay of DPP-4. [ABSTRACT FROM AUTHOR]

The hyperactivity of urease enzyme is associated with clinically important complications including stomach ulcers and kidney stones. This enzyme provides a suitable environment to Helicobacter pylori at low pH in the stomach, a causative agent of peptic and ulcer gastric that may lead to cancer. Natural and synthetic small molecules were reported to inhibit urease enzyme. Within this context, a new series of 1,4-benzodioxane-based thiosemicarbazones (3a-p) were synthesized and screened in vitro against urease enzyme to elucidate their anti-urease activity. All the compounds displayed potent inhibitory potential with IC 50 values ranging between 3.65 ± 2.64 to 31.9 ± 1.094 μM, under positive control of thiourea (IC 50 = 20.8 ± 0.75 μM). Structural activity relationship (SAR) has revealed a variation based on substituents pattern at R group. The results of docking study suggest that these compounds thermodynamically binds via nickel atoms present in the active-site of urease. The in silico docking analysis and our experimental findings are in excellent co-relation. The pharmacokinetic behavior of all the compounds were also predicted. Image 1 • A new series 1,4-benzodioxane-based Thiosemicarbazones derivatives (3a-p) were synthesized. • The structures were confirmed by 1H NMR, 13C NMR, ESI-MS, and single crystal X-ray diffraction. • All compounds showed significant inhibition with IC 50 values in range of 3.65–31.9 μ M. • The structure-activity relationship were predicted by molecular docking. • Molecular docking studies were performed to know the binding interaction at atomic level. [ABSTRACT FROM AUTHOR]

Fourteen triterpene acids, viz., three tirucallane-type (1–3), eight ursane-type (4–11), two oleanane-type (12, 13) and one lupane type (21), along with boswellic aldehyde (14), α-amyrine (15), epi-amyrine (16), straight chain acid (17), sesquiterpene (19) and two cembrane-type diterpenes (18, 20) were isolated, first time, from the methanol extract of Boswellia elongata resin. Compound (1) was isolated for first time as a natural product, while the remaining compounds (2‒21) were reported for first time from B. elongata. The structures of all compounds were confirmed by advanced spectroscopic techniques including mass spectrometry and also by comparison with the reported literature. Eight compounds (1–5, 11, 19 and 20) were further screened for in vitro α-glucosidase inhibitory activity. Compounds 3–5 and 11 showed significant activity against α-glucosidase with IC50 values ranging from 9.9–56.8 μM. Compound 4 (IC50 = 9.9 ± 0.48 μM) demonstrated higher inhibition followed by 11 (IC50 = 14.9 ± 1.31 μM), 5 (IC50 = 20.9 ± 0.05 μM) and 3 (IC50 = 56.8 ± 1.30 μM), indicating that carboxylic acid play a key role in α-glucosidase inhibition. Kinetics studies on the active compounds 3–5 and 11 were carried out to investigate their mechanism (mode of inhibition and dissociation constants Ki). All compounds were found to be non-competitive inhibitors with Ki values in the range of 7.05 ± 0.17–51.15 ± 0.25 µM. Moreover, in silico docking was performed to search the allosteric hotspot for ligand binding which is targeted by our active compounds investigates the binding mode of active compounds and it was identified that compounds preferentially bind in the allosteric binding sites of α-glucosidase. The results obtained from docking study suggested that the carboxylic group is responsible for their biologic activities. Furthermore, the α-glucosidase inhibitory potential of the active compounds is reported here for the first time. [ABSTRACT FROM AUTHOR]

Drug induced liver damage remains a prevalent concern in healthcare and may reduce the effectiveness of therapy by compromising therapeutic regimens. Many Commiphora species are known for their medicinal properties, and some of them are used traditionally for hepatoprotective effect. In the course of our drugs discovery from natural sources, phytosterols (lophenol (Lop) and lathosterol (Lat)), isolated from Commiphora kua were studied to evaluate their hepatoprotective effects in acetaminophen (APAP) induced hepatotoxicity in mice. To evaluate the hepatoprotective effects of phytosterols isolated from C. kua using in vivo experimental model. Mice of either sex were divided into 7 groups: Vehicle, silymarin (SLY), acetaminophen (APAP), Lop 25, Lop 50, Lat 25, Lat 50 (n = 5). Vehicle group received only vehicle (0.1% DMSO solution) for 7 days, APAP group received single dose of acetaminophen on day 7 and SLY group received silymarin for 7 days. Lop 25 and Lop 50 received low and high doses of Lop (25 μg/kg BW and 50 μg/kg BW), respectively, for 7 days, while Lat 25 and Lat 50 received low and high doses of Lat (25 μg/kg BW and 50 μg/kg BW) for 7 days. On day 7, all animals except Vehicle group kept fasted for 18 h and received APAP i. p. 400 mg/kg BW. After 20 h of APAP administration, the animals anesthetized with light chloroform and scarified by cervical decapitation. The blood serum and liver tissue samples were collected for biochemical and histopathological analysis. Liver function tests (LFTs) including lactate deydrogenase (LDH), alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST) and direct bilirubin) were used as biochemical parameters. While catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH) were taken as anti-oxidant enzymes. Significant increase in levels of ALT, AST, ALP, LDH and direct bilirubin, and significant decrease in concentration of anti-oxidant enzymes (SOD, CAT and GSH) was observed in APAP-treated group. Similarly, histological slides showed obvious signs of damage to liver cells, reflecting acetaminophen induced hepatotoxicity. Treatment of test animals with phytosterols resulted in significant recovery of LFTs profile and concentration of anti-oxidant enzymes. Similarly, significant improvement of liver tissues was noted in histological analysis. Both phytosterols possessed hepatoprotective potential and should be further evaluated for acute toxicity studies and pharmacokinetics/pharmacodynamics profile. Image 1 [ABSTRACT FROM AUTHOR]

• A novel series of (R)-4-fluorophenyl-1 H -1,2,3-triazole derivatives (8a-n) were synthesized. • The structures were confirmed by 1H NMR, 13C NMR, 19F NMR, ESI-MS, and single crystal X-ray diffraction. • All compounds displayed significant α -glucosidase inhibition with IC 50 values of 17.9–193.7 µM. • Molecular docking studies were performed to establish their structure-activity relationship and binding interaction at atomic level. Diabetes is a non-communicable disease, which occurs either due to the lack of insulin or the inability of the human body to recognize it. The recent data indicates an increase in the trend of people diagnosed with Type 2 diabetes mellitus (T2DM). α -Glucosidase inhibitors are known to reduce the impact of carbohydrates on blood glucose level and prevent the digestion of carbohydrates. α -glucosidase inhibitors hold great potential for the treatment of T2DM. In search of better α -glucosidase inhibitors, a series of novel (R)-4-fluorophenyl-1 H -1,2,3-triazole derivatives were synthesized (6 and 8a-n) and evaluated for their α -glucosidase inhibitory activity in vitro. All new compounds were characterized by 1H NMR, 13C NMR, 19F NMR, ESI-MS, and where applicable by single crystal X-ray diffraction (8 m). A preliminary structure-activity relationship suggested that the presence of 1 H -1,2,3-triazole ring in (R)-4-fluorophenyl-1 H -1,2,3-triazole derivatives has remarkable contribution in the overall activity. Molecular docking studies were carried out to investigate the binding mode of compounds within the active site of the α -glucosidase enzyme. Docking results are in complete agreement with the experimental finding. This study unravelled a new class of triazole derivatives with α -glucosidase inhibitory activity. [ABSTRACT FROM AUTHOR]

COVID-19 appeared as a highly contagious disease after its outbreak in December 2019 by the virus, named SARS-CoV-2. The threat, which originated in Wuhan, China, swiftly became an international emergency. Among different genomic products, spike protein of virus plays a crucial role in the initiation of the infection by binding to the human lung cells, therefore, SARS-CoV-2's spike protein is a promising therapeutic target. Using a combination of a structure-based virtual screening and biochemical assay, this study seeks possible therapeutic candidates that specifically target the viral spike protein. A database of ~ 850 naturally derived compounds was screened against SARS-CoV-2 spike protein to find natural inhibitors. Using virtual screening and inhibitory experiments, we identified acetyl 11-keto-boswellic acid (AKBA) as a promising molecule for spike protein, which encouraged us to scan the rest of AKBA derivatives in our in-house database via 2D-similarity searching. Later 19 compounds with > 85% similarity with AKBA were selected and docked with receptor binding domain (RBD) of spike protein. Those hits declared significant interactions at the RBD interface, best possess and excellent drug-likeness and pharmacokinetics properties with high gastrointestinal absorption (GIA) without toxicity and allergenicity. Our in-silico observations were eventually validated by in vitro bioassay, interestingly, 10 compounds (A3, A4, C3, C6A, C6B, C6C, C6E, C6H, C6I, and C6J) displayed significant inhibitory ability with good percent inhibition (range: > 72-90). The compounds C3 (90.00%), C6E (91.00%), C6C (87.20%), and C6D (86.23%) demonstrated excellent anti-SARS CoV-2 spike protein activities. The docking interaction of high percent inhibition of inhibitor compounds C3 and C6E was confirmed by MD Simulation. In the molecular dynamics simulation, we observed the stable dynamics of spike protein inhibitor complexes and the influence of inhibitor binding on the protein's conformational arrangements. The binding free energy ΔG TOTAL of C3 (-38.0 ± 0.08 kcal/mol) and C6E (-41.98 ± 0.08 kcal/mol) respectively indicate a strong binding affinity to Spike protein active pocket. These findings demonstrate that these molecules particularly inhibit the function of spike protein and, therefore have the potential to be evaluated as drug candidates against SARS-CoV-2., (© 2024. The Author(s).)

In recent decades, nanopores have become a promising diagnostic tool. Protein and solid-state nanopores are increasingly used for both RNA/DNA sequencing and small molecule detection. The latter is of great importance, as their detection is difficult or expensive using available methods such as HPLC or LC-MS. DNA aptamers are an excellent detection element for sensitive and specific detection of small molecules. Herein, a method for quantifying small molecules using a ready-to-use sequencing platform is described. Taking ethanolamine as an example, a strand displacement assay is developed in which the target-binding aptamer is displaced from the surface of magnetic particles by ethanolamine. Non-displaced aptamer and thus the ethanolamine concentration are detected by the nanopore system and can be quantified in the micromolar range using our in-house developed analysis software. This method is thus the first to describe a label-free approach for the detection of small molecules in a protein nanopore system., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Prolyl specific oligopeptidase (POP), is one of the highly expressed enzymes in the brain and is a prime target to treat disorders related to the central nervous system. Here, we describe the structure-based design of the tacrine derivatives, selective, and brain-permeable POP inhibitors. These compounds inactivate POP in-vitro specifically and sustainably at very low concentrations (nano molar). Among this series, compound 6b (IC 50 = 0.81 ± 0.04 µM) exhibited most potent inhibition. Furthermore, kinetic study revealed that these molecules target active site of POP which is further confirmed by in-silico molecular interaction analysis. The computational docking results indicates that the compounds are well fitted in the active site with high binding score (i.e., > -7 to > -4 kcal/mol) where Trp595, Arg643, Tyr473, and Ser554 plays important role in binding with the active compounds. The molecular dynamic simulation of most active compounds ( 6a , 6b , 6d , and 6f ) displayed higher free energy binding, when compared to the standard drug in MM-PBSA based binding free energy calculation. In addition, the predicted pharmacokinetic profile suggests that these compounds can serve as excellent inhibitors upon additional optimization which makes them prime choice for further investigation.Communicated by Ramaswamy H. Sarma.

This study aimed to develop a local 3 D-printed bioactive graft using poly-caprolacton (PCL) as a drug carrier and 3- O -acetyl-β-boswellic acid (β-ABA) as an anticancer compound. β-ABA-loaded 3 D-printed scaffold was fabricated and physically characterized. The results indicated more desirable mechanical and physical properties of the β-ABA-loaded PCL mat in comparison with the PCL scaffold. Following sustained release of β-ABA, the β-ABA-loaded PCL scaffold revealed selective cytotoxic activity against melanoma cells, while the PCL + ABA with the bolus delivery of β-ABA was toxic against fibroblast cells. Followed by the induction of apoptosis in melanoma cells at the gene level, the result of the western blot showed that the β-ABA-loaded scaffold significantly up-regulated P53 and down-regulated BCL2, with an increment in the ratio of Bax/BCL2. The selective anti-cancer properties of β-ABA-loaded 3 D printed scaffold against melanoma cells indicated that this scaffold could be potentially used as a bioactive graft to improve the melanoma treatment.

This study aimed to compare the effect of Boswellic acid derivatives on the viability, apoptosis, and epigenomic profiling of breast cancer. According to the viability assays, 3-O-acetyl-11-keto-β-Boswellic acid (AKBA) showed more toxicity against MDA-MB-231 cells when compared with the 3-O-acetyl-β-Boswellic acid (ABA). In contrast, ABA revealed less toxicity against MCF-10A. Cell cycle and apoptosis assays determined the maximum apoptotic effect of AKBA on MCF-7, and MDA-MB-231 cells. Interestingly, β-Boswellic acid (BA) and ABA did not promote the apoptosis in MCF-10A cells. Transwell migration assay indicated the greatest normalized inhibition (around 160%) in the migration of MDA-MB-231 cells induced by AKBA. The expression of P53, BAX, and BCL2 genes in cancerous cell lines has affirmed that both AKBA and ABA could induce the maximal apoptosis. Western-blot investigation demonstrated that the maximum over-expression of P53 protein (1.96 times) was caused by AKBA in MDA-MB-231 cells, followed by ABA in MCF-7 cells. The BCL2 protein expression was in agreement with the previously reported results. The global DNA methylation in both cancerous cells was reduced by ABA. These results suggest that ABA represented more epigenetic modulatory effect while AKBA shows more cytotoxic and apoptotic effect against breast cancer cell lines., (© 2022. The Author(s).)

A series of new para -terphenyls derivatives have been efficiently synthesized by a ligand-free heterogeneous Pd/C-catalyzed two-fold Suzuki-Miyaura coupling reaction. Methyl 5-bromo-2-iodobenzoate was selected to react with a variety of different aryl boronic acids ( 2a-i ). Nine new p -terphenyl derivatives ( 3a - i ) were prepared and the structures were confirmed by several analytical techniques including infrared, spectroscopy, 1 H and 13 C NMR spectroscopy, mass spectrometry, and in the case of compound 3 b, by X-ray diffraction method. The new derivatives were obtained in very good yields (78-91%). This synthetic facile route is envisioned to improve the preparation of p -terphenyl-based natural products.

Cancer is a leading cause of death worldwide. Proper efficient drugs are required to treat this deadly disease. Natural products have long been a vital source of anticancer agents and they have generated various "lead compounds" suitable for drug developments. With the recent advancement of chemical synthesis and bioevaluation techniques, these lead compounds of natural origins have been utilized for the production of useful anticancer drugs. Among the naturally occurring bioactive compounds, various O-heterocycles have been evaluated as remarkable cancer therapeutic agents. These compounds generally possess unique structures and novel mechanisms of action. In the present review article, some selected O-heterocycles as promoting anticancer agents have been discussed in brief. Various natural sources and chemistry, as well as bioactivities of these compounds, have been described. The development of improved analogues of these compounds through synthetic modifications and efficient bioevaluation, along with proper studies on structure-activity relationship and mechanism of actions, has been mentioned. The article has demonstrated the recent relevance of naturally occurring O-heterocyclic compounds in the current anticancer drug discovery and development scenario., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The development of anti-cancer drugs with the ability to inhibit brain metastasis through the blood-brain barrier (BBB) is substantially limited due to the lack of reliable in vitro models., Main Methods: In this study, the Geltrex-based Transwell and microfluidic BBB models were applied to screen the effect of β-boswellic acid (β-BA) on the metastasis of MDA-MB-231 cells through the BBB in static and dynamic conditions, respectively., Major Results: The toxicity assay revealed that β-BA deteriorates MDA-MB-231 cells, while β-BA had no detectable toxic effects on human umbilical vein endothelial cells (HUVECs) and astrocytes. Trans-endothelial electrical resistance evaluation showed sustainable barrier integrity upon treatment with β-BA. Vimentin expression in HUVECs, evaluated using western blot, confirmed superior barrier integrity in the presence of β-BA. The obtained results were confirmed using an invasion study with a cell tracker and a scanning electron microscope. β-BA significantly inhibited metastasis by 85%, while cisplatin (Cis), a positive control, inhibited cancer cell migration by 12% under static conditions. Upon applying a dynamic BBB model, it was revealed that β-BA-mediated metastasis inhibition was significantly higher than that mediated by Cis., Conclusions and Implications:  In summary, the current study proved the anti-metastatic potential of β-BA in both static and dynamic BBB models., (© 2021 Wiley-VCH GmbH.)

Herein, a series of novel 1 H -1,2,3-triazole and carboxylate derivatives of metronidazole ( 5a-i and 7a-e ) were synthesized and evaluated for their antimicrobial activity in vitro. All the newly synthesized compounds were characterized by 1 H NMR, 13 C NMR, HRMS, and 19 F NMR ( 5b , 5c and 5h ) spectroscopy wherever applicable. The structures of compounds 3 , 5c and 7b were unambiguously confirmed by single crystal X-ray analysis diffraction method. Single crystal X-ray structure analysis supported the formation of the metronidazole derivatives. The antimicrobial (antifungal and antibacterial) activity of the prepared compounds was studied. All compounds (except 2 and 3 ) showed a potent inhibition rate of fungal growth as compared to control and metronidazole. The synthetic compounds also showed higher bacterial growth inhibiting effects compared to the activity of the parent compound. Amongst the tested compounds 5b , 5c , 5e , 7b and 7e displayed excellent potent antimicrobial activity. The current study has demonstrated the usefulness of the 1 H -1,2,3-triazole moiety in the metronidazole skeleton., (Copyright © 2021, Avula et al.)

A series of novel 1 H -1,2,3-triazole analogs ( 9a-j ) were synthesized via "Click" chemistry and Suzuki-Miyaura cross-coupling reaction in aqueous medium. The compounds were evaluated for their carbonic anhydrase-II enzyme inhibitory activity in vitro . The synthesis of triazole 7a was accomplished using ( S )-(-) ethyl lactate as a starting material. This compound ( 7a) underwent Suzuki-Miyaura cross-coupling reaction with different arylboronic acids in aqueous medium to afford the target molecules, 9a-j in good yields. All newly synthesized compounds were characterized by 1 H NMR, 13 C NMR, FT-IR, HRMS, and where applicable 19 F NMR spectroscopy ( 9b , 9e , 9h , and 9j ). The new compounds have shown moderate inhibition potential against carbonic anhydrase-II enzyme. A preliminary structure-activity relationship suggested that the presence of polar group at the 1 H -1,2,3-triazole substituted phenyl ring in these derivatives ( 9a-j ) has contributed to the overall activity of these compounds. Furthermore, via molecular docking, it was deduced that the compounds exhibit inhibitory potential through direct binding with the active site residues of carbonic anhydrase-II enzyme. This study has unraveled a new series of triazole derivatives as good inhibitors against carbonic anhydrase-II., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Avula, Khan, Halim, Khan, Al-Riyami, Csuk, Das and Al-Harrasi.)

Psoriasis is a chronic autoimmune disease that affects 2-3% of the global population and requires an effective treatment. Frankincense has been long known for its potent anti-inflammatory activities. In this study, a structural bioinformatics approach was used to evaluate the efficacy of individual active components of frankincense, macrocyclic diterpenoid derivatives ( 1 - 27 ), and boswellic acids ( 28 - 46 ) in the treatment of psoriasis. Initially, major druggable targets of psoriasis were identified. Subsequently, structure-based screening was employed by using three different docking algorithms and scoring functions (MOE, AutoDock Vina, and MVD) for the target fishing of compounds against 18 possible targets of psoriasis. Janus Kinase 1, 2, 3 (JAK 1/2/3), eNOS, iNOS, interleukin-17 (IL-17), and Tumor necrosis factor-α (TNF-α) were identified as the preferred molecular targets for these compounds. This computational analysis reflects that frankincense diterpenoids and triterpenoids can serve as excellent anti-psoriatic agents by targeting major cytokines (TNF-α, IL-17, IL-13, IL-23, and IL-36γ,) exacerbated in psoriasis, and inflammatory pathways particularly JAK1/2/3, eNOS, iNOS, MAPK2, and IFNγ. The results were compared with the reported experimental findings which correlates well with our in-silico verdicts., (Copyright © 2020 Halim, Khan, Csuk, Al-Rawahi and Al-Harrasi.)

Introduction: Incensole can be considered as a biomarker for Boswellia species which is a diterpene that has received remarkable pharmacological interest recently due to its potent anti-inflammatory and anti-depressant activity., Objective: Near-infrared (NIR) spectroscopy coupled with PLSR (partial least squares regression) as a robust, rapid and alternative method was used to quantify the content of incensole in three species namely B. papyrifera, B. sacra and B. serrata and cross-validated by high-performance liquid chromatography (HPLC)., Materials and Methods: NIR spectrophotometer was used for the quantification of incensole standards and Boswellia species in absorption mode in the wavelength range between 700 and 2500 nm. A PLSR model was built from the obtained spectral data using 70% of the incensole working standard solutions (training set), ranging from 0.5 to 100 ppm. The PLSR model obtained has a R 2 value of 98% with a correlationship of 0.99 and a good prediction with root mean square error for prediction (RMSEP) value of 3.2%., Results: The results indicated that the methanol (MeOH) extract of B. papyrifera resin has the highest concentration of incensole (18.4%) followed by n-hexane (13.5%) and ethyl acetate (3.6%) while trace amounts was detected in the fractions of B. sacra and no incensole was detected in the fractions of B. serrata., Conclusion: The findings are in total agreement with the HPLC analysis suggesting that NIR spectroscopy coupled with PLSR is a robust, rapid and non-destructive alternate method for the quantification of incensole in B. papyrifera. Copyright © 2018 John Wiley & Sons, Ltd., (Copyright © 2018 John Wiley & Sons, Ltd.)