Open AccessDesign, Molecular Docking and Biological Evaluation of Fused Thienopyrimidines and Quinazoline
Author(s) -
S. Kaliraj,
R. Jeyalakshmi,
M. Kathiravan,
Thirumurthy Madhavan,
Arikketh Devi
Publication year - 2021
Publication title -
asian journal of chemistry/asian journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.145
H-Index - 34
eISSN - 0975-427X
pISSN - 0970-7077
DOI - 10.14233/ajchem.2021.23062
Subject(s) - quinazoline , chemistry , pyrimidine , docking (animal) , stereochemistry , mtt assay , thiophene , potency , combinatorial chemistry , cell growth , in vitro , biochemistry , organic chemistry , medicine , nursing
The anticancer activity of the condensed pyrimidine and quinazoline moieties are pronounced with adifferent pathway. Thienopyrimidine is considered as ring equivalent bioisosteres of quinazolines andpresent in other heterocyclic compounds including thienopyrimidine. The present investigation focusedon the synthesis of thienopyrimidine and quinazoline derivatives for their anticancer activity against thehuman oral squamous carcinoma-3 (HSC-3) cell line. The synthesized compound confirmed for theirstructural 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 theinhibition of cancer cells. Further probing by docking studies revealed that the compounds exhibitpossible interactions with VEGF, FGFR and c-Met proteins, which are known to have a role in thepathogenesis of oral squamous cell carcinoma. Among the derivatives a moderate activity demonstratedby substituted 4-chloro-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]-pyrimidine (4a) and ethyl2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (1a) derivatives. Lack of chirality andthe presence of bulky substituents in few of the compounds were found to be the cause for lowerpotency.