Novel quinoxalinyl chalcone hybrid scaffolds as enoyl ACP reductase inhibitors: Synthesis, molecular docking and biological evaluation

• Published in: Bioorganic & medicinal chemistry letters 2017-05, Vol.27 (10), p.2174-2180
• Main Authors: Desai, Vidya, Desai, Sulaksha, Gaonkar, Sonia Naik, Palyekar, Uddesh, Joshi, Shrinivas D., Dixit, Sheshagiri K.
• Format: Article
• Language: English
• Subjects: Anti-cancer; Anti-Infective Agents - chemical synthesis; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Anti-tubercular; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - toxicity; Binding Sites; Candida albicans - drug effects; Cell Proliferation - drug effects; Chalcones; Chalcones - chemical synthesis; Chalcones - chemistry; Chalcones - pharmacology; Disk Diffusion Antimicrobial Tests; Drug Design; Enoyl-CoA Hydratase - antagonists & inhibitors; Enoyl-CoA Hydratase - metabolism; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Escherichia coli - drug effects; Humans; MCF-7 Cells; Molecular docking; Molecular Docking Simulation; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - enzymology; Protein Structure, Tertiary; Quinoxaline; Staphylococcus aureus - drug effects
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2017.03.059

[Display omitted] We report herein, first ever synthesis of series of novel differently substituted quinoxalinyl chalcones using Claisen Schmidt condensation, its molecular docking studies, and potential to be good anti-microbial, anti-tubercular and anti-cancer agents. The antimicrobial studies were carried out against Staphylococcus aureus, Escherichia coli and Candida albicans using disc diffusion procedure. The selected chalcones were tested for anti-cancer and cytotoxicity activity against MCF-7 cancer cell line using MTT assay method. All the synthesized compounds were screened for in vitro anti-tubercular screening against MtbH37RV strains by Alamar blue dye method. These results were compared with molecular docking studies carried out on Mycobacterium tuberculosis enzyme enoyl ACP reductase using Surflex-Dock program that is interfaced with Sybyl-X 2.0. SAR analysis for antimicrobial and antitubercular activity has also been proposed.