Synthesis of heteroannulated cyclopent[b]indoles: Exploration of in vitro cytotoxicity and molecular docking studies

ABSTRACT

A series of novel cyclopent[b]indole analogues that hold isoxazolo-, pyrido-templates were designed and synthesized in good yields. The in vitro cytotoxicity was concerned for all the newly synthesized compounds by MTT assay against HeLa (cervix adeno carcinoma) and MCF-7 (breast cancer). These synthesized compounds were further compared with the standard drug ellipticine, 5-fluorouracil, cisplatin, and methotrexate. The synthesized heteroannulated cyclopent[b]indole compounds were found to show better cytotoxic activity against HeLa and MCF-7 with primary structure activity relationship studies. To identify with the nature of interactions of these molecules, we performed molecular docking studies using the protein kinase CK2 inhibitors. The docking results afforded some valuable information for the future design of more potent inhibitors.

GRAPHICAL ABSTRACT

KEYWORDS:

• CK2 inhibitors
• HeLa and MCF-7
• isoxazolo-cyclopent[b]indole
• pyrido-cyclopent[b]indole

Acknowledgments

Rajendran Satheeshkumar is grateful to the University Grant Commission (UGC-SAP), New Delhi, for BSR—Senior Research Fellowship, which is thankfully acknowledged. Dr. K. J. Rajendra Prasad greatly acknowledged UGC-Emeritus fellowship (No. F.6-6/2015-17/EMERITUS-2015-17-OBC-7410/(SAII), Dated: 21.09.2015) for research.

Supplementary data

CIF file for compounds 4d has been deposited with the Cambridge Crystallographic Data Centre as CCDC number 1047624. Copy of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK. [Fax: [phone] o. E-mail: [email protected].