Design, synthesis, docking and mechanistic studies of new thiazolyl/thiazolidinylpyrimidine-2,4-dione antiproliferative agents

In this article, we display on the synthesis and biological evaluation of a new series of thiazolylpyrimidine 3a-l and thiazolidinylpyrimidine derivatives 5a-e. The structures of the new compounds were confirmed by using different spectral techniques including NMR, IR, mass spectroscopy in addition to elemental analyses. The cell viability of the new compounds was assessed against normal human mammary gland epithelial (MCF-10A) cell line. Data revealed that none of the compounds examined exhibited cytotoxic effects, and the cell viability for the compounds examined at 50 mM was greater than 87%. The antiproliferative activity of 3a-l and 5a-e was evaluated against four human cancer cell lines where the compounds showed promising activity. The most potent derivatives were compounds 3a, 3c, 3f, 3i, and 5b with GI50 values ranging from 0.90 mM to 1.70 mM against the four cancer cell lines in comparison to doxorubicin (GI50 = 1.1 0 mM). Compounds 3a, 3c and 3i showed potent antiproliferative activity with dual inhibitory action against EGFR and BRAFV600E. Compounds 3a, 3c, and 3i demonstrated promising AutoDock scores towards EGFR and BRAFV600E with values of - 9.1 and - 8.6, -9.0 and - 8.5, and - 8.4 and - 8.0 kcal/mol, respectively. The physicochemical and pharmacokinetic characteristics of 3a, 3c, and 3i were anticipated, demonstrating their oral bioavailability.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open

Automated summary

This article presents the synthesis and biological evaluation of a new series of thiazolylpyrimidine and thiazolidinylpyrimidine derivatives. The structures of the compounds were confirmed through various spectral techniques. The compounds showed no cytotoxic effects and exhibited promising antiproliferative activity against human cancer cell lines. Some of the compounds demonstrated dual inhibitory action against EGFR and BRAFV600E.