Synthesis and evaluation of novel derivatives with anticancer activities: benzoxazole-linked 1,3,5-triazine thioethers, Isatin-based compounds

ABSTRACT

This study integrates the synthesis, characterization, and biological evaluation of two classes of compounds: Isatin derivatives, and benzoxazole-linked 1,3,5-triazine thioethers. For synthesis of substituted 4,6-bis(benzo[d]oxazol-2-ylthio)-N-phenyl-1,3,5-triazine-2-amine derivatives, condensation of 2-aminophenol using carbon disulfide in the presence of potassium hydroxide gave the benzo[d]oxazole-2-thiol. On the other side, 2,4,6-trichloro-1,3,5-triazine and various substituted aniline were put into the reaction, yielding various substituted 4,6-dichloro-N-phenyl-1,3,5-triazine-2-amine derivatives (P-01 to P-12). Finally, both intermediates react with each other and forms final triazine derivatives (JHP-01 to JHP-12). For the synthesis of Isatin derivatives, Isatin and 2-chloro-N-(4-(3-oxomorpholino)phenyl)acetamide was used to yield 2-(2,3-dioxoindolin-1-yl)-N-(4-(3-oxomorpholino) phenyl)acetamide. Further reaction with various substituted anilines to form substituted (E)-2-(2-oxo-3-(phenylimino)indolin-1-yl)-N-(4-(3-oxomorpholino)phenyl)acetamide (MMP-01 to MMP-12). A detailed comparison of their anticancer activities against the MCF-7 human breast cancer cell line highlights their therapeutic potential. Isatin and triazine derivatives demonstrated IC50 values as low as ~1.7 mg/mL. This comprehensive study underscores the structural features critical for anticancer efficacy and provides a framework for future medicinal chemistry research. Synthesis is confirmed using mass spectra, IR spectra, ¹H NMR and ¹³C NMR.

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WSN 202 (2025) 34-64

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