Abstract

IN SILICO INHIBITION OF PROTO-ONCOGENE TYROSINE PROTEIN KINASE SRC (C-SRC) BY ARISTOLACTAM A II, 4-ALLYL RESORCINOL AND STIGMAST-4-EN-3, 6-DIONE FOR ANTICANCER ACTIVITY OF PIPER BETLE LINN. (PIPERACEAE): TRADITIONAL CLAIM REVALIDATED

Paulomi Paul, Abhishek Chowdhury* and Manabendra Dutta Choudhury

Abstract

Plant based compounds serve as curing agents of various disease for decades. Virtual screening using computational tools provide a wide platform of plant based bioactivity prediction. The current study provides molecular mechanism of compound isolated from roots of Piper betle. This work comprises of target prediction and molecular mechanism of Aristolactam A II (ARL), 4-allyl resorcinol (ARL) and Stigmast-4-en-3, 6-dione (STM), compounds isolated from P. betle root. The target validation showed proto-oncogene tyrosine protein kinase Src (c-Src) and cyclin dependent kinases (CDK) as the topranked targets. Molecular docking of ARL showed good score against c-Src (-17.88 Kcal/mol) and CDK2 (-16.96 Kcal/mol) using Biosolveit LeadIT. Autodock 4.2 validation also showed similar amino acid pattern. Comparison with known c-Src inhibitor Bosutinib (BST) (-27.70 Kcal/mol) and CDK2 inhibitor Staurosporine (STP) (-35.20 Kcal/mol) showed similarity in binding pattern. Toxicity study showed ARL was non-toxic whereas Bosutinib (BST) was reported with high side-effect and toxicity. This concludes that these compounds works as some of the factors to support the ethnomedicinal claim of anticancer activity of P. betle.

Keywords: Piper betle; Aristolactam A II; 4-allyl resorcinol; Stigmast-4-en-3,6-dione; proto-oncogene tyrosine protein kinase Src; Cyclin dependent kinase 2; c-Src inhibitor; CDK2 inhibitor; molecular docking.