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

[ Vol. 21 , Issue. 2 ]

Author(s):

Sanal Dev*, Sunil. R. Dhaneshwar and Bijo Mathew*   Pages 138 - 148 ( 11 )

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.

Keywords:

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

Affiliation:

Department of Pharmaceutical Chemistry, Al Shifa College of Pharmacy, Perintalmanna, Kerala 679325, Department of Pharmaceutical Chemistry, B.V.D.U Poona College of Pharmacy, Pune, Maharashtra, Division of Drug Design and Medicinal Chemistry Research Lab., Department of Pharmaceutical Chemistry, Ahalia School of Pharmacy, Palakkad -678557, Kerala



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