title: Some new indole-coumarin hybrids; Synthesis, anticancer and Bcl-2 docking studies.
abstract: Hybrid molecules have attracted attention for their improved biological activity, selectivity and lesser side effects profile, distinct from their individual components. In the quest for novel anticancer drug entities, three series of indole-coumarin hybrids - 3-(1-benzyl-1H-indol-2-yl)-2H-chromen-2-ones, 2-(2-oxo-2H-chromen-3-yl)-1H-indole-3-carbaldehydes and 2-(2-oxo-2H-chromen-3-yl)-1H-indole-3-carboxylic acids were synthesized. All the synthesized compounds were characterized by spectral techniques like IR, (1)H NMR, (13)C NMR, mass spectrometry and elemental analysis. In silico docking studies of synthesized molecules with apoptosis related gene Bcl-2 that is recognized to play an important role in tumerogenesis were carried out. Dose-dependent cytotoxic effect of the compounds in human breast adenocarcinoma (MCF-7) and normal cell lines were assessed using MTT assay and compared with that of the standard marketed drug, Vincristine. Compound 4c had a highly lipophilic bromine substituent capable of forming halogen bond and was identified as a potent molecule both in docking as well as cytotoxicity studies. Flow cytometric cell cycle analysis of 4c exhibited apoptotic mode of cell death due to cell cycle arrest in G2/M phase. Structure activity relationship of these hybrid molecules was also studied to determine the effect of steric and electronic properties of the substituents on cell viability.
authors.affiliation: Department of Chemistry, Manipal Institute of Technology, Manipal University, 576 104, India.
authors.forename: Pooja R
authors.initials: PR
authors.lastname: Kamath
authors.affiliation: Department of Chemistry, Manipal Institute of Technology, Manipal University, 576 104, India. Electronic address: dhanyadss3@gmail.com.
authors.forename: Dhanya
authors.initials: D
authors.lastname: Sunil
authors.affiliation: Department of Atomic and Molecular Physics, Manipal Institute of Technology, Manipal University, 576 104, India.
authors.forename: A Abdul
authors.initials: AA
authors.lastname: Ajees
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, 576 104, India.
authors.forename: K S R
authors.initials: KS
authors.lastname: Pai
authors.affiliation: Department of Radiation Biology & Toxicology, School of Life Sciences, Manipal University, 576 104, India.
authors.forename: Shubhankar
authors.initials: S
authors.lastname: Das
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D061986:MCF-7 Cells; D015394:Molecular Structure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D007211:Indoles; D019253:Proto-Oncogene Proteins c-bcl-2; C030123:coumarin
keywords: Apoptosis; Bcl-2; Cytotoxicity; Indole–coumarin