Discovery of 2‐Amino‐4H‐1, 3, 4‐thiadiazine‐5(6H)‐one Derivatives and Their In Vitro Antitumor Investigation
Faten Z. Mohammed, Youstina William Rizzk, Ibrahim M. El‐Deen, Emad M. Gad, Mohammed El Behery, Ahmed R. E. Mahdy
Abstract
Abstract Novel 2‐Amino‐4H‐1,3,4‐thiadiazine‐5‐(6H)‐one derivatives 3 – 6 were designed, synthesized, and assessed for their anticancer effects on MCF‐7 and A549 cell lines. The cytotoxicity screening found several active compounds. Meanwhile, compound 5 b exhibited the strongest cytotoxic activity compared to Doxorubicin (DOX). Furthermore, DNA flow cytometry investigation over MCF‐7 cells indicated that compound 5 b demonstrated arrest at G1/S stages of the cell cycle and induction of apoptosis by rising pre‐G1 stage. In addition, the underlying mechanistic studies of compound 5b ′s proapoptotic activities revealed that they induced the elevation of P53 and the BAX/BCL‐2 ratio expression that led to a rise in active Caspase 3/7 levels and triggered apoptosis. Finally, Compound 5 b displayed a significant dual topoisomerase IIβ enzyme and β‐tubulin polymerization inhibition.