Virtual Combinatorial Library Design, Synthesis and In vitro Anticancer Assessment of -2-Amino-3-Cyanopyridine Derivatives

Title:Virtual Combinatorial Library Design, Synthesis and In vitro Anticancer Assessment of -2-Amino-3-Cyanopyridine Derivatives

Volume: 21 Issue: 2

Author(s): Sanal Dev*, Sunil. R. Dhaneshwar and Bijo Mathew*

Affiliation:

• Department of Pharmaceutical Chemistry, Al Shifa College of Pharmacy, Perintalmanna, Kerala 679325,India

• Division of Drug Design and Medicinal Chemistry Research Lab., Department of Pharmaceutical Chemistry, Ahalia School of Pharmacy, Palakkad -678557, Kerala,India

Keywords: Virtual screening, topoisomerase II, combiGlide, SRB protein assay, derivatives.

Abstract: Aim and Objective: For the development of new class of anticancer agents, a series of novel 2-amino-3-cyanopyridine derivatives were designed from virtual screening with Glide program by setting Topoisomerase II as the target.

Materials and Methods: The top ranked ten molecules from the virtual screening were synthesized by microwave assisted technique and investigated for their cytotoxic activity against MCF-7 and A- 549 cell lines by using sulforhodamine B assay method.

Results: The most active compound 2-amino-4-(3,5-dibromo-4-hydroxyphenyl)-6-(2,4- dichlorophenyl) nicotinonitrile (CG-5) showed significant cytotoxic profile with (LC50 = 97.1, TGI = 29.9 and GI50 = <0.1 µM) in MCF-7 and (LC50= 93.0, TGI= 50.0 and GI50= <7 µM) in A-549 cell lines. A molecular docking study was performed to explore the binding interaction of CG-5with the active site of Topoisomerase II.

Conclusion: It can be concluded that halogen substituent pyridine ring was benefit for cytotoxicity.

Cite this article as:

Dev Sanal *, Dhaneshwar R. Sunil. and Mathew Bijo *, Virtual Combinatorial Library Design, Synthesis and In vitro Anticancer Assessment of -2-Amino-3-Cyanopyridine Derivatives, Combinatorial Chemistry & High Throughput Screening 2018; 21 (2) . https://dx.doi.org/10.2174/1386207321666180228113925