Kovashnee Naicker

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, characterization, and cytotoxic and antimicrobial activities of ruthenium(II) arene complexes with N,N-bidentate ligands

Abstract Three new complexes, [(η6-C6H6)RuCl(C5H4N-2-CH=N-Ar)]PF6 (Ar = phenylmethylene (1), (4-methoxyphenyl)methylene (2), and phenylhydrazone (3)), were prepared by reacting [(η6-C6H6)Ru(μ-Cl)Cl]2 with N,N′-bidentate ligands in a 1 : 2 ratio. Full characterization of the complexes was accomplished using 1H and 13C NMR, elemental and thermal analyses, UV–vis and IR spectroscopy and single crystal X-ray structures. Single crystal structures confirmed a pseudo-octahedral three-legged, piano-stool geometry around Ru(II), with the ligand coordinated to the ruthenium(II) through two N atoms. The cytotoxicity of the mononuclear complexes was established against three human cancer cell lines and selectivity was also tested against non-cancerous human epithelial kidney (HEK 293) cells. The compounds were selective toward the tumor cells in contrast to the known anti-cancer drug 5-fluoro uracil which was not selective between the tumor cells and non-tumor cells. All the compounds showed moderate activity against MCF7 (human breast adenocarcinoma), but showed low antiproliferative activity against Caco-2 and HepG2. Also, antimicrobial activities of the complexes were tested against a panel of antimicrobial-susceptible and -resistant Gram-negative and Gram-positive bacteria. Of special interest is the anti-mycobacterial activity of all three synthesized complexes against Mycobacterium smegmatis, and bactericidal activity against resistant Enterococcus faecalis and methicillin-resistant Staphylococcus aureus ATCC 43300.

Synthesis, Molecular Docking Study and in vitro Anticancer Activity of Tetrazole Linked Benzochromene Derivatives.

BACKGROUND Globally, cancer is regarded as one of the biggest health concern in humans and animals and is one of the most terrifying diseases. Therefore, there is a necessity for the discovery, development and improvement of novel antitumor drug molecules which could efficiently prevent proliferative pathways and clonal expansion of cells. Heterocyclic compounds like benzochromene play a key role in the development of current pharmaceuticals, natural resources, agriculture products, analytical reagents and dyes. Therefore, anticancer drugs show increased resistance, it is essential to designing the novel structured heterocyclic moieties to create potential anticancer agents with promising biological applications. OBJECTIVE To synthesis a novel 1-(substitutedphenyl)-2-(1H-tetrazol-5-yl)-1H-benzo[f]chromene-3-amine derivatives for in vitro antitumour activity. METHOD The reaction of 3-amino-1-(substitutedphenyl)-1H-benzo[f]chromene-2-carbonitrile with sodium azide, ammonium chloride in dimethyl formamide solvent under reflux condition for 4 h afforded products (3a-k). The synthesized molecules were subjected to possible potential anti-tumour activity in vitro in four human cancer cell lines (MCF-7, Caco-2, HeLa and SKBR-3), and one human non-cancer cell line (HEK293), using the MTT cell viability assay. RESULTS A novel series of products (3a-k) were synthesized with good yield and were identified with 1H NMR, 15N NMR, 13C NMR, FT-IR and HR-MS spectrum. The most potent compounds 3d, 3e, and 3f possessing the greatest cytotoxicity activity with IC50 values slightly higher (15-33 μM) than that of 5-Fluorouracil (10-17 μM), indicating their potential to be antitumor agents. The 3a, 3b, 3c, 3h, 3i and 3j compounds showed moderate activity. Additionally, a molecular docking analysis was conducted to predict the multi-drug resistance modulator behavior of synthesized compounds in the ATP binding site of P-glycoprotein. CONCLUSIONS We synthesized and designated eleven novel derivatives of tetrazole linked benzochromenes (3a-k) and evaluated their anti-cancer activity. Additionally, the results from the docking studies were found to be in good agreement with the results from computational profiling.

Synthesis, characterization, antiproliferative, and antimicrobial activity of osmium(II) half-sandwich complexes

Abstract New osmium(II)-arene complexes [(η6-C6H6)OsCl(C5H4N-2-CH=N-C6H5X)](PF6) (X = p-flouro (1), p-chloro (2), p-methyl (3)) were synthesized by reaction of the corresponding bidentate N,N′-ligands with the osmium-arene precursor [(η6-C6H6)Os(μ-Cl)Cl]2 in a 2:1 ratio. These complexes were characterized by UV–Vis, IR, 1H, 13C NMR spectroscopy, and elemental analysis and, for compound 1, a single crystal X-ray structure was also obtained. The complexes were investigated for antiproliferative activity in vitro against MCF-7 (human breast adenocarcinoma), Caco-2 (human epithelial colorectal adenocarcinoma), and HepG2 (human hepatocellular carcinoma) tumor cell lines. To test their selectivity, the non-tumor HEK293 (human embryonic kidney) cell line was used. The compounds were selective toward the tumor cell lines when compared to the known anticancer drug 5-fluorouracil which displayed low selectivity. The compounds were substantially more active against Caco-2 than 5-fluorouracil. They also showed moderate activity against the other two tumor cell lines. In addition, the antimicrobial activity of complex 2 was explored against a panel of antimicrobial-susceptible and -resistant Gram-negative and Gram-positive bacteria. Complex 2 showed anti-mycobacterial activity against Mycobacterium smegmatis and bactericidal activity against drug-resistant Enterococcus faecalis and methicillin-resistant Staphylococcus aureus ATCC 43300.