ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Synthesis of thiazole linked pyrimidine and chalcone derivatives: in-vitro anticancer studies and in-silico molecular docking simulations

Gajjela Venkata Nageswara Rao, Reddymasu Sreenivasulu, Mandava Bhuvan Tej, Mandava Bhagya Tej, Dontina Ganga Bhavani, Ravikumar Kapavarapu, and Mandava V. Basaveswara Rao

Department of Chemistry, Krishna University, Machilipatnam, India

E-mail: professormandava@gmail.com

Abstract:

The synthesis of thiazole linked pyrimidine and chalcone derivatives 20a-j was achieved by the Claisen-condensation reaction between thiazole-aldehyde and different types of aryl ketones in the presence of piperidine in ethanol at reflux for 12 h time. These derivatives were tested for their cytotoxicity values against MCF-7, A2780, A549 and Colo-205 cell lines with Etoposide as standard drug by utilizing MTT reduction assay protocol. Among the synthesized derivatives, the derivative 20a with 3,4,5-trimethoxyaryl ring showed superior anticancer effect on all cell lines, with IC₅₀ values from MCF-7 = 0.05 ± 0.007 µM; A549 = 0.11 ± 0.047 µM; Colo-205 = 0.66 ± 0.062 µM and A2780 = 0.96. ± 0.075 µM. Molecular docking studies targeting human Topoisomerase IIβ revealed that several synthesized compounds, 20a, 20b, 20f, 20 g, and 20j exhibited notable binding affinities (− 5.9 to − 5.5 kcal/mol) in comparison to the standard drug Etoposide (− 6.5 kcal/mol). These candidates showed favourable interactions with critical active site residues such as GLN778, ASP479, ARG503, and MET782, which are crucial for stabilizing the topoisomerase–DNA complex. The interaction patterns suggest a potential mechanism for modulation at the protein-DNA interface. Among these, compound 20a exhibited a favourable binding and interaction profile, positioning it as a promising hit for the development of novel anticancer therapeutics.

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Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-025-04554-y

Chemical Papers 80 (3) 2819–2838 (2026)