Mehbub Momin

Novel 2-(1-(substitutedbenzyl)-1H-tetrazol-5-yl)-3-phenylacrylonitrile derivatives: synthesis, in vitro antitumor activity and computational studies

This work describes the two-step synthesis of new series of 2-(1-(substitutedbenzyl)-1H-tetrazol-5-yl)-3-phenylacrylonitrile derivatives (6a–k) starting from substituted benzyl halides (5a–k) and 3-phenyl-2-(1H-tetrazol-5-yl)acrylonitrile (4). Initially, compound 4 was synthesized using benzaldehyde, malononitrile and sodium azide. All the synthesized compounds were obtained in good yields and were characterized using 1H NMR, 13C NMR, FTIR and HRMS spectral data. The new compounds (6a–k) were evaluated for their potential in vitro antitumor activity against four human cancer cell lines (MCF-7, CaCO2, HeLa and SkBr3) by MTT assay. The most potent compounds 6b, 6h and 6j show good activity (IC50 values) relative to 5-fluorouracil, with potential to be antitumor agents. Compounds 6a, 6c, 6g, 6f and 6k showed moderate activity. The best performing three compounds (6b, 6h and 6j) were evaluated for in silico analysis on the PharmMapper web server, and the human mitogen-activated protein kinase 1 (MEK-1) enzyme was recognized as the main target protein. MEK-1 inhibition by these compounds was further confirmed by the docking study to corroborate the target.Graphical Abstract

SYNTHESIS AND ANTIOXIDANT EVALUATION OF NOVEL PHENOTHIAZINE LINKED SUBSTITUTEDBENZYLIDENEAMINO-1,2,4-TRIAZOLE DERIVATIVES

ABSTRACT A series of novel 5-((10 H -phenothiazin-10yl)methyl)-4-(substitutedbenzylideneamino)-4 H -1,2,4-triazole-3-thiol derivatives (6a-i) have been synthesized from compound (1) through a multi-step reaction. The key intermediate (5) afforded a series of title compounds (6a–i) on condensation with various suitable aldehydes in the presence of H 2 SO 4 . The structures of novel compounds were characterized based on their elemental analysis, IR, 1 H-NMR, 13 C-NMR and MS spectral data. All these novel compounds were screened for their in vitro antioxidant activity by employing nitric oxide, hydrogen peroxide, and DPPH radical scavenging assays. The compounds 6d, 6e and 6i demonstrated potent antioxidant activity as these contain the electron-releasing groups. Keywords: Synthesis, Anti-oxidant activity, 1,2,4-Triazole, Phenothiazines. INTRODUCTION The heterocyclic compounds chemistry continues to be an emerging field in the organic and pharmaceutical chemistry 1 . Heterocyclic compounds are present in various drugs, several natural products, some vitamins, biomolecules, and biologically active compounds such as anti-inflammatory, antitumour, antimalarial, antidepressant, anti-HIV, antibiotic and antimicrobial agents etc

The synthesis, structural elucidation and antimicrobial activity of 2- and 4-substituted-coumarinyl chalcones.

Coumarinyl chalcones are hybrid molecules combining the skeletal frameworks of coumarins (aromatic lactones) and chalcones (aromatic α,β-unsaturated carbonyl compounds). Both these skeletal frameworks are found abundantly in nature and may have a role to play in themedicinal effects of the extracts of plants. Because both coumarins and chalcones each have a variety of medicinal properties, combining both these pharmacophores into one molecule could result in either enhanced activity of each of their properties individually or a broader spectrum of medicinal properties than either of them on their own. These hybrid heterocyclic molecules were first synthesized from 3-acetyl coumarin and substituted benzaldehydes by the Claisen–Schimdt condensation carried out in an alcoholic solvent and using either an ionic or organic base. This has been a popular method for synthesizing coumarinyl chalcones; however, variations such as microwave solvent free synthesis have been carried out with decreased reactions times and optimized yields. Although the preferred method has been to use bases such as sodium hydroxide and piperidine, a greener approach involving cellulose sulphonic acid as a catalyst was also employed. Hybrid coumarinyl chalcones have recently shown anticancer, antioxidant, analgesic, antiinflammatory and antibacterial activity and when complexed with Ni and Cu together with fluoroquinolones, played a part in developing highly active anticancer and antioxidant complexes. This is not surprising, because the two pharmacophores individually have shown activity in all these assays. To our knowledge, there have been no reports on docking studies with coumarinyl chalcones to any of the known protein targets which we have used in this work; however, chalcones themselves have been docked to the HIV-integrase enzyme and the colchine region of tubulin, where the carbonyl group was found to be essential for docking. Coumarins have been docked to the COX-1 and COX-2 enzymes and themetabolic enoyl-ACP-reductase enzyme of bacteria. There are no reports of coumarinyl chalcones being docked to the penicillin binding protein 2X (PBP 2X) used in this study. We herein report the synthesis and antibacterial activity of coumarinyl chalcones and explore the effect that chloro, fluoro, hydroxy, methoxy and prenyl groups have on activity as well as determine which of the 2 or 4 positions were better for substitution with

Synthesis and Evaluation of Novel Fluorinated 2-Styrylchromones as Antibacterial Agents

A range of fluorinated 2-styrylchromones (5a–g) of which six were new (5a–f) were prepared in three steps using the Baker-Venkataraman rearrangement along with two methoxylated derivatives (5h-i) and a methylenedioxy derivative (5j) and screened for their antibacterial activity using Gram-positive bacteria (Staphylococcus aureus, sciuri, and xylosus as well as Bacillus subtilis) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumonia). The compounds were most effective against B. subtilis followed by S. aureus and a single strain of E. coli (ATCC 25922). Difluorination on the phenyl ring was shown to enhance antibacterial activity, and fluorine substitution at the 6 position was shown to be far superior to substitution at the 7 position. In comparison to tetracycline, the activity indices of the fluorinated styrylchromones ranged from 0.50 to 0.75 against B. subtilis. The crystal structure of 2′-fluoro-2-styrylchromone is also presented, and the molecule was shown to be planar.

Structure elucidation of a series of fluoro-2-styrylchromones and methoxy-2-styrylchromones using 1D and 2D NMR spectroscopy.

2-Styrylchromones (2-SCs) are a chemical family of oxygen heterocyclic compounds, similar to the flavonoids (2-phenylchromones), but with a vinyl group bridging the chromone ring to the phenyl moiety. Many derivatives of 2-SCs have been synthesized, and their occurrence in nature has also been reported. There have also been numerous reports on the biological activity of the synthesized derivatives of 2-SCs, which has recently been reviewed by Gomes et al., and these compounds were seen to have antioxidant, antiviral, anticancer, antiallergic, and hepatoprotective activity and shown to be A3 adenosine receptor antagonists and xanthine oxidase inhibitors. Although the NMR data for 2-SCs are always reported in synthetic publications that also report the biological activity, full structural elucidation of these compounds is rare. We have only noticed one publication on the structural elucidation of this class of compounds in which the nitro derivatives were described. To the best of our knowledge, there are no publications where the structural elucidation of these compounds has been discussed with substituents on the aromatic rings that donate electrons by resonance into the aromatic rings. Furthermore, the structural elucidation of fluorinated molecules is more challenging because of F being NMR active and coupling with both the protons and the carbon atoms. We have recently reported the synthesis and antibacterial activity of these compounds and herein report the structural elucidation of seven fluorinated, two methoxylated, and a methylenedioxy derivative of 2-SC along with their cinnamoyloxyacetophenone and 3-hydroxy-2,4-pentadien-1-one intermediates. The structural elucidation and NMR data reported here can help one identify newly isolated or synthesized derivatives of 2-SCs, especially fluorinated derivatives.

2-Acetyl-phenyl (2E)-3-(4-fluoro-phen-yl)acrylate.

In the title compound, C17H13FO3, the dihedral angle between the benzene rings is 70.34 (5)°. In the crystal, molecules are linked via pairs of bifurcated C—H⋯(O,O) hydrogen bonds, forming inversion dimers. These dimers are linked via C—H⋯O and C—H⋯F interactions, forming a three-dimensional structure.

6-Hy-droxy-2H-1,3-benzodioxole-5-carbaldehyde.

The title compound, C8H6O4, crystallizes with two independent molecules in the asymmetric unit. The benzodioxole ring system is almost planar in each molecule, with maximum deviations of 0.008 (1) and 0.007 (1) Å. The molecular structure is characterized by strong electrostatic intramolecular O⋯O contacts [2.649 (3) Å] and intramolecular O—H⋯O hydrogen-bonding interactions. Intermolecular O⋯O interactions [3.001 (2) Å] are observed in the crystal structure.