Synthesis of novel heterocyclic compounds containing pyrimidine nucleus using the Biginelli reaction: Antiproliferative activity and docking studies

Abstract

In a single reaction step, pyrimidine derivatives (4a‐p) were synthesized from the triple reaction of aromatic aldehydes (1), ethyl cyanoacetate (2), and some guanyl hydrazone derivatives (3a‐n). These compounds were tested as in vitro against two types of cancerous cell lines, namely, a human colon cancerous cell line (DLD‐1) and a human breast cancerous cell line (MDA‐MB‐231). According to the obtained results, nearly all the compounds have cytotoxic activity in the tested cell lines. Especially, the compounds 4j, 4k, and 4n had a significant effect against DLD‐1. Furthermore, compounds 4g, 4m, and 4o exhibited lower IC50 values compared to other synthesized compounds against MDA‐MB‐231. We hope that these compounds can be improved as anticancer agents in the future. Molecular docking was performed according to both topoisomerase I and N‐acetyltransferase 1 proteins to examine theoretically the binding mode and site of pyrimidine compounds having the best activity.

Multicomponent Reaction-Assisted Drug Discovery: A Time- and Cost-Effective Green Approach Speeding Up Identification and Optimization of Anticancer Drugs

“…In 2020, the study by Yavuz et al [ 141 ] aimed at developing an effective, improved and easy method to synthesize substituted pyrimidine-5-carbonitriles, without the isolation of their intermediates. In a single reaction step, pyrimidine derivatives were synthesized from the triple reaction of aromatic aldehydes, ethyl cyanoacetate and a few guanyl hydrazone derivatives ( Scheme 19 ).…”

Synthesis, Molecular Docking and Antiproliferative Activity Studies of a Thiazole‐Based Compound Linked to Hydrazone Moiety

“…In our constant effort to develop potent anticancer agents with low cytotoxicity [20–22] . The significance of these scaffolds the thiazole ring and the hydrazone moiety in development of potent anticancer agents has motivated us to synthesize a compound that consist of thiazole ring and hydrazone in one molecule and investigate its in vitro activity in two different cancer cell lines which are the HepG2 (liver hepatocellular carcinoma cell line) and DLD‐1 (human colon cancer cell line).…”