IMR Press / FBL / Volume 26 / Issue 4 / DOI: 10.2741/4911

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Studies in molecular modeling, in vitro CDK2 inhibition and antimetastatic activity of some synthetic flavones
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1 Department of Pharmaceutical Chemistry, Principal K. M. Kundnani College of Pharmacy, Cuffe-Parade, Mumbai 400 005, Maharashtra, India
2 Gude Lab, Cancer Research Institute, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai 410 210, Maharashtra, India
3 Department of Pharmaceutical Science and Technology, Institute of Chemical Technology, Matunga, Mumbai - 400019, Maharashtra, India
Send Correspondence to: Urmila J. Joshi, Department of Pharmaceutical Chemistry, Principal K. M. Kundnani College of Pharmacy,Cuffe-Parade, Mumbai-400 005, Maharashtra,India, Tel: 91-9869612731, Fax: 91-22-22165282, E-mail:
Front. Biosci. (Landmark Ed) 2021, 26(4), 664–681;
Published: 1 October 2020
(This article belongs to the Special Issue Structural genomics of human kinome)

Naturally occurring flavonoids have been shown to possess anticancer activity. We have previously shown that certain synthetic flavonoids also exert significant antiproliferative potential in MOLT-4, MCF-7, and HepG2 cell lines. To this end, we evaluated eight synthetic flavones for their CDK2 binding by molecular docking. Most flavones showed interaction with Leu 83. Based on docking and antiproliferative activity, we chose 3’-nitroflavone and 3’, 5’-dimethoxyflavone for the molecular dynamics (MD) simulation and CDK2 inhibition studies. MD simulation studies confirmed interactions with CDK2 (as observed in docking). Furthermore, the inhibitory activities of CDK2/cyclin A2 enzyme for 3’-nitroflavone and 3’, 5’-dimethoxyflavone were found to be 6.17 and 7.19 μM, respectively. 3’-nitroflavone and 3’, 5’-dimethoxyflavone displayed moderate activity in colony formation assay, wound-scratch assay, and Leighton tube studies. Based on these data, the synthesized flavones might have clinical potential as potential inhibitors of CDK2.

Molecular docking
MD simulation
Figure 1
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