Design, Molecular Docking and Biological Evaluation of Fused Thienopyrimidines and Quinazoline

S. Kaliraj1,, R. Jeyalakshmi1,*,, M.K. Kathiravan2,, T. Madhavan3, and Arikketh Devi3,

1Department of Chemistry, SRM Institute of Science & Technology, Kattankulathur-603203, India

2Department of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM Institute of Science & Technology, Kattankulathur-603203, India

3Department of Genetic Engineering, School of Bio-Engineering, SRM Institute of Science & Technology, Kattankulathur-603203, India

*Corresponding author: E-mail: jeyalakr@srmist.edu.in; rajyashree64@gmail.com

Abstract

The anticancer activity of the condensed pyrimidine and quinazoline moieties are pronounced with a different pathway. Thienopyrimidine is considered as ring equivalent bioisosteres of quinazolines and present in other heterocyclic compounds including thienopyrimidine. The present investigation focused on the synthesis of thienopyrimidine and quinazoline derivatives for their anticancer activity against the human oral squamous carcinoma-3 (HSC-3) cell line. The synthesized compound confirmed for their structural characteristics from spectral analysis and tested for anti-proliferative activity from MTT assay. The electron-withdrawing group in 4-chloro thienopyrimidines and amino ester derivate/facilitate the inhibition of cancer cells. Further probing by docking studies revealed that the compounds exhibit possible interactions with VEGF, FGFR and c-Met proteins, which are known to have a role in the pathogenesis of oral squamous cell carcinoma. Among the derivatives a moderate activity demonstrated by substituted 4-chloro-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]-pyrimidine (4a) and ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (1a) derivatives. Lack of chirality and the presence of bulky substituents in few of the compounds were found to be the cause for lower potency.

Keywords

Thienopyrimidines, Quinazoline, lactams, Anti-proliferative activity, Molecular docking.

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