Momin Khan

Synthesis of novel inhibitors of β-glucuronidase based on benzothiazole skeleton and study of their binding affinity by molecular docking.

Benzothiazole derivatives 1-26 have been synthesized and their in vitro β-glucuronidase potential has been evaluated. Compounds 4 (IC(50)=8.9 ± 0.25 μM), 5 (IC(50)=36.1 ± 1.80 μM), 8 (IC(50)=8.9 ± 0.38 μM), 13 (IC(50)=19.4 ± 1.00 μM), 16 (IC(50)=4.23 ± 0.054 μM), and 18 (IC(50)=2.26 ± 0.06 μM) showed β-glucuronidase activity potent than the standard (d-saccharic acid 1,4-lactone, IC(50)=48.4 ± 1.25 μM). Compound 9 (IC(50)=94.0 ± 4.16 μM) is found to be the least active among the series. All active analogs were also evaluated for cytotoxicity and none of the compounds showed any cytotoxic effect. Furthermore, molecular docking studies were performed using the gold 3.0 program to investigate the binding mode of benzothiazole derivatives. This study identifies a novel class of β-glucuronidase inhibitors.

Evaluation of bisindole as potent β-glucuronidase inhibitors: Synthesis and in silico based studies

Bisindole analogs 1-17 were synthesized and evaluated for their in vitro β-glucuronidase inhibitory potential. Out of seventeen compounds, the analog 1 (IC50=1.62±0.04 μM), 6 (IC50=1.86±0.05 μM), 10 (IC50=2.80±0.29 μM), 9 (IC50=3.10±0.28 μM), 14 (IC50=4.30±0.08 μM), 2 (IC50=18.40±0.09 μM), 19 (IC50=19.90±1.05 μM), 4 (IC50=20.90±0.62 μM), 7 (IC50=21.50±0.77 μM), and 3 (IC50=22.30±0.02 μM) showed superior β-glucuronidase inhibitory activity than the standard (d-saccharic acid 1,4-lactone, IC50=48.40±1.25 μM). In addition, molecular docking studies were performed to investigate the binding interactions of bisindole derivatives with the enzyme. This study has identified a new class of potent β-glucouronidase inhibitors.

2,4,6-Trichlorophenylhydrazine Schiff Bases as DPPH Radical and Super Oxide Anion Scavengers

Syntheses of thirty 2,4,6-trichlorophenylhydrazine Schiff bases 1-30 were carried out and evaluated for their in vitro DPPH radical and super oxide anion scavenging activities. Compounds 1-30 have shown a varying degree of DPPH radical scavenging activity and their IC50 values range between 4.05-369.30 µM. The compounds 17, 28, 18, 14, 8, 15, 12, 2, 29, and 7 exhibited IC50 values ranging between 4.05±0.06-24.42±0.86 µM which are superior to standard n-propylgallate (IC50=30.12±0.27 µM). Selected compounds have shown a varying degree of superoxide anion radical scavenger activity and their IC50 values range between 91.23-406.90 µM. The compounds 28, 8, 17, 15, and 14, showed IC50 values between 91.23±1.2-105.31±2.29 µM which are superior to standard n-propylgallate (IC50=106.34±1.6 µM).

Synthesis of Benzophenonehydrazone Schiff Bases and their In Vitro Antiglycating Activities

Benzophenonehydrazone Schiff bases 1-25 were synthesized and their in vitro antiglycation potential has been studied. Out of twenty-five compounds, thirteen showed varying degrees of antiglycation activity with IC50 values ranging between 25.7 - 305 μM, if compared with the standard rutin (IC50 = 70.5 ± 0.50 μM). Compounds 21 (2,3- dihydroxybenzaldehyde N-(diphenylmethylene)hydrazine) IC50 = 25.7 ± 0.003 μM, 14 (diphenylmethanone N-[1-(2,4- dihydroxy-5-nitrophenyl)ethylidene]hydrazine) IC50 = 36.6 ± 0.004 μM, 6 (3,4-dihydroxybenzaldehyde N- (diphenylmethylene)hydrazine) IC50 = 49.5 ± 0.001 μM, 13 (diphenylmethanone N-[1-(2,5-dihydroxyphenyl)ethylidene] hydrazine) IC50 = 52.6 ± 0.023 μM, and 15 (diphenylmethanone N-[1-(3,4-dihydroxyphenyl)ethylidene]hydrazine) IC50 = 57 ± 0.002 μM, showed showed much better antiglycation potential superior to the standard rutin. The compounds 7 (2,5- dihydroxybenzaldehyde N-(diphenylmethylene)hydrazine) IC50 = 66 ± 0.002 μM, and 25 (diphenylmethanone N-[1-(2,5- dihydroxyphenyl)propylidene] hydrazine) IC50 = 67.9 ± 0.001 μM showed compareably good antiglycation activity to standard rutin. All compounds were characterized by spectroscopic techniques and gave satisfactory elemental analysis.

Molecular modeling-based antioxidant arylidene barbiturates as urease inhibitors.

Previously we have reported arylidene barbiturates 1-18 as a novel class of antioxidants; however, their urease inhibitory potential has not yet been explored. In this communication, molecular docking studies were used to predict the potential ligands from compounds 1-18 which culminated in the identification of certain new urease inhibitors. Ligands were screened in vitro for their urease inhibitory potential. Compound 1, as deduced from modeling studies, was found to be the most active urease inhibitor (13.0 ± 1.2 μM), when compared with the standard thiourea (IC₅₀=21.1 ± 0.3 μM). All of the compounds were found to be nontoxic to Artemia salina in brine shrimp lethality bioassay.

Synthesis and structure–activity relationship of thiobarbituric acid derivatives as potent inhibitors of urease

A series of thiobarbituric acid derivatives 1-27 were synthesized and evaluated for their urease inhibitory potential. Exciting results were obtained from the screening of these compounds 1-27. Compounds 5, 7, 8, 11, 16, 17, 22, 23 and 24 showed excellent urease inhibition with IC50 values 18.1 ± 0.52, 16.0 ± 0.45, 16.0 ± 0.22, 14.3 ± 0.27, 6.7 ± 0.27, 10.6 ± 0.17, 19.2 ± 0.29, 18.2 ± 0.76 and 1.61 ± 0.18 μM, respectively, much better than the standard urease inhibitor thiourea (IC₅₀=21 ± 0.11 μM). Compound 3, 4, 10, and 26 exhibited comparable activities to the standard with IC₅₀ values 21.4 ± 1.04 and 21.5 ± 0.61 μM, 22.8 ± 0.32, 25.2 ± 0.63, respectively. However the remaining compounds also showed prominent inhibitory potential The structure-activity relationship was established for these compounds. This study identified a novel class of urease inhibitors. The structures of all compounds were confirmed through spectroscopic techniques such as EI-MS and (1)H NMR.

Discovery of novel oxindole derivatives as potent α-glucosidase inhibitors.

A series of 6-chloro-3-oxindole derivatives 1-25 were synthesized in high yields by the reaction of 6-chlorooxindole with different aromatic aldehydes in the presence of piperidine. All the synthesized compounds were isolated with E configuration. The structures were confirmed using spectroscopic techniques, including (1)H NMR and EIMS. These compounds showed varying degree of yeast α-glucosidase inhibition and seven were found as potent inhibitors of the enzyme. Compounds 2, 3, 4, 5, 6, 23, and 25 exhibited IC50 values 2.71±0.007, 11.41±0.005, 37.93±0.002, 15.19±0.004, 24.71±0.007, 17.33±0.001, and 14.2±0.002μM, respectively, as compared to standard acarbose (IC50, 38.25±0.12μM). Docking studies helped to find interactions between the enzyme and the active compounds. As a result of this study, oxindoles have been discovered as a new class of α-glucosidase inhibitors which have not been reported earlier.

Identification of potent urease inhibitors via ligand- and structure-based virtual screening and in vitro assays

A pharmacophore model was developed based on three structurally diverse urease inhibitors by using the GASP program. This model comprises the positions and tolerance for two acceptor atoms (AA1 and AA2), one donor atom (DA1), and one hydrophobic center (HYP1). This derived phamacophore model was employed to screen an in-house database of organic compounds. Hits obtained were evaluated by molecular docking using GOLD software. On the basis of ligand- and structural-based predictions, an in vitro testing of short-listed compounds was conducted and a novel class of urease inhibitors (2-aminothiophines) was identified. The potent in vitro activity and selectivity of these compounds, along with their non-toxic nature against the plant cells indicated that they can serve as leads for solving urease-associated health and agriculture problems.

Benzimidazole, coumrindione and flavone derivatives as alternate UV laser desorption ionization (LDI) matrices for peptides analysis

BackgroundMatrix-assisted laser desorption/ionization (MALDI) is a soft ionization mass spectrometric technique, allowing the analysis of bio-molecules and other macromolecules. The matrix molecules require certain characteristic features to serve in the laser desorption/ionization mechanism. Therefore, only a limited number of compounds have been identified as ultraviolet- laser desorption/ionization (UV-LDI) matrices. However, many of these routine matrices generate background signals that useful information is often lost in them. We have reported flavones, coumarindione and benzimidazole derivatives as alternate UV-LDI matrices.ResultsThirty one compounds have been successfully employed by us as matrices for the analysis of low molecular weight (LMW) peptides (up to 2000 Da). Two peptides, bradykinin and renin substrate tetra-decapeptide were analyzed by using the newly developed matrices. The MS measurements were made after mixing the matrix solution with analyte by using dried droplet sample preparation procedures. The synthesized matrix materials showed better S/N ratios and minimal background signals for low mass range. Furthermore, pico molar concentrations of [Glu1]-fibrinopeptide B human could be easily analyzed with these matrices. Finally, BSA-digest was analyzed and identified through database search against Swiss-Prot by using Mascot.ConclusionsThese results validate the good performance of the synthesized UV-laser desorption/ionization (LDI) matrices for the analysis of low molecular weight peptides.

In vitro enzyme inhibition activities of Myrtus communis L.

The crude methanolic extract and chloroform, ethyl acetate and n-butanol fractions of Myrtus communis L. were examined as inhibitors of acetylcholinesterase, butyrylcholinesterase and lipoxygenase. A significant enzyme inhibition activity (81 to 91%) was shown by the crude methanolic extract and its fractions against acetylcholinesterase, while high to outstanding enzyme inhibitory activity (72.5 to 99%) was shown against butyrylcholinesterase. The crude methanolic extract and its various fractions also demonstrated significant activity (79 to 94.5%) against lipoxygenase.