Design and Efficient Synthesis of New 4-Amino-Substituted 2-(4-Bromobenzyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines of Anticancer Interest and Their In Silico Study
Sahil Arora
a
Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Sciences and Natural Products, School of Pharmaceutical Sciences, Central University of Punjab, Bathinda 151 401, India
,
Shikha Thakur
a
Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Sciences and Natural Products, School of Pharmaceutical Sciences, Central University of Punjab, Bathinda 151 401, India
,
Venkata Rao Kaki
b
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, India
a
Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Sciences and Natural Products, School of Pharmaceutical Sciences, Central University of Punjab, Bathinda 151 401, India
› InstitutsangabenS.A. and R.K. thank the Indian Council of Medical Research (ICMR, grant No. 45/24/2022-DDI/BMS) and Department of Science and Technology, Promotion of University Research and Scientific Excellence (DST-PURSE) (SR/PURSE/2023/220(C)) for funding. The authors acknowledge instrumentation funding provided by DST-FIST to the department. The NMR facility provided by the Central Instrumentation Laboratory (CIL) is also acknowledged.
Thienopyrimidines are an emerging class of fused pyrimidines due to their broad spectrum of pharmacological properties, including antimicrobial, anti-inflammatory, antimalarial, anticancer, etc. The anticancer activity of these compounds has been mechanistically proven via the inhibition of validated drug targets, such as EGFR, VEGFR-2, PI3K, and c-kit. In this research article, we designed and synthesized new 4-amino-substituted 2-(4-bromobenzyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines to explore their anticancer potential. These heterocycles were designed based on pharmacophoric features of the core heterocycle, varying its C4 substitution with a variety of amines and considering cancer protein-ligand interactions with the aim to obtain potent lead molecules. The target compound-protein interaction complexes were analyzed, and lead compounds were identified based on their better binding affinity in molecular docking studies.
