SYNTHESIS OF NOVEL IMIDAZOLE AND FUSED IMIDAZOLE DERIVATIVES AS CYTOTOXIC AND ANTIMICROBIAL AGENTS: MOLECULAR DOCKING AND BIOLOGICAL EVALUATION

Objectives: The objective of this work is to synthesize novel imidazole and fused imidazole derivatives using 5-arylidene-2-hydrazino-3-phenyl imidazolin-4-ones (5a-c) as key intermediate. The structure of the newly synthesized compounds was characterized using IR, 1HNMR, Mass spectroscopy, elemental analysis and some representative 13CNMR.Methods: The target compounds were synthesized starting from 5-arylidene-2-hydrazino-3-phenyl imidazolin-4-ones (5a-c) which prepared from the appropriate 5-arylidene-2-(methylthio)-3-phenyl imidazolin-4-ones (3a-c). Several synthetic pathways were be used for the preparation of the targets. Some of the newly synthesized compounds were evaluated for their cytotoxic activity against breast carcinoma and colon carcinoma cell lines. On the other hand, the antimicrobial activity evaluation of some newly prepared compounds was performed using cup plate diffusion method.Results: Compound 5c was the most active one against breast carcinoma (IC50=3.3 ug/ml) and colon carcinoma cell lines (IC50=4.73 ug/ml) when compared with doxorubicin as standard. Molecular docking studies further supported the highest potency of 5c and further help understanding the various interactions between the ligand and enzyme active sites. On the other hand, the antimicrobial activity evaluation showed that most of the evaluated compounds exhibited broad spectrum activity.Conclusion: The present work led to the development of promising antitumor compounds containing substituted imidazolidin-5-one or imidazotriazol-6-one skeletons. Compounds 5c showed the highest potency at low µg/ml level against breast MCF-7 and colon HCT116 cell lines. On the other hand, most of the newly synthesized compounds showed broad spectrum antimicrobial activity when cup plate diffusion method was performed.Â

An Efficient Greener Approach for N-acylation of Amines in Water Using Benzotriazole Chemistry

A straightforward, mild and cost-efficient synthesis of various arylamides in water was accomplished using versatile benzotriazole chemistry. Acylation of various amines was achieved in water at room temperature as well as under microwave irradiation. The developed protocol unfolds the synthesis of amino acid aryl amides, drug conjugates and benzimidazoles. The environmentally friendly synthesis, short reaction time, simple workup, high yields, mild conditions and free of racemization are the key advantages of this protocol

In Vitro Antimycobacterial Activity and Physicochemical Characterization of Diaryl Ether Triclosan Analogues as Potential InhA Reductase Inhibitors

Two sets of diphenyl ether derivatives incorporating five-membered 1,3,4-oxadiazoles, and their open-chain aryl hydrazone analogs were synthesized in good yields. Most of the synthesized compounds showed promising in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv. Three diphenyl ether derivatives, namely hydrazide 3, oxadiazole 4 and naphthylarylidene 8g exhibited pronounced activity with minimum inhibitory concentrations (MICs) of 0.61, 0.86 and 0.99 μg/mL, respectively compared to triclosan (10 μg/mL) and isoniazid (INH) (0.2 μg/mL). Compounds 3, 4, and 8g showed the InhA reductase enzyme inhibition with higher IC50 values (3.28–4.23 µM) in comparison to triclosan (1.10 µM). Correlation between calculated physicochemical parameters and biological activity has been discussed which justifies a strong correlation with respect to the inhibition of InhA reductase enzyme. Molecular modeling and drug-likeness studies showed good agreement with the obtained biological evaluation. The structural and experimental information concerning these three InhA inhibitors will likely contribute to the lead optimization of new antibiotics for M. tuberculosis

Development of Isatin-Based Schiff Bases Targeting VEGFR-2 Inhibition: Synthesis, Characterization, Antiproliferative Properties, and QSAR Studies

Three sets of isatin-based Schiff bases were synthesized utilizing the molecular hybridization approach. Some of the synthesized Schiff bases show significant to moderate antiproliferative properties against MCF7 (breast), HCT116 (colon), and PaCa2 (pancreatic) cancer cell lines with potency compared to reference drugs 5-fluorouracil (5-FU) and Sunitinib. Among all, compound 17 f (3-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)imino)-1-((1-(2-methoxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methylindolin-2-one) exhibits promising antiproliferative properties against the MCF7 cancer cell line with 2.1-fold more potency than Sunitinib. However, among all the synthesized compounds, three (5-methylisatin derivatives) were the most effective against HCT116 in comparison to 5-FU. Compound 17 f exhibited the highest anti-angiogenic effect on the vasculature as it significantly reduced BV from 43 mm to 2 mm in comparison to 5.7 mm for Sunitinib and flow cytometry supports the arrest of the cell cycle at G1/S phases. In addition, compound 17 f also showed high VEGFR-2 inhibition properties against breast cancer cell lines. Robust 2D-QSAR studies supported the biological data