Discovery of 2‐Amino‐4H‐1, 3, 4‐thiadiazine‐5(6H)‐one Derivatives and Their In Vitro Antitumor Investigation

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.

In vivo anticancer study of sodium 2‐[(4‐oxidobenzylidene)amino]‐6H‐1,3,4‐thiadiazine‐5‐olate against Ehrlich ascites carcinoma via targeting PI3K/mTOR pathway

“…In continuation with our research studies focusing on the synthesis and in vitro investigation of bioactive compounds with anticancer activity, we had concluded that 1,3,4‐thiadiazine derivatives are a potential hypothesis in the field of medicinal chemistry and drug industry (Mohammed et al., 2022). Several of the synthesized components were also noted to be efficient when investigated in vitro versus breast (MCF‐7) and lung (A549) cancer cell lines for their ability to inhibit cell proliferation.…”

“…All experimental groups' livers and kidneys served as the source of the specimens for the histopathological analysis, which were then sectioned, embedded in paraffin, preserved in 10% neutral buffered formalin, tainted with hematoxylin and eosin stain (H&E), and examined under a microscope condition (Mohamed et al., 2021; Mohamed, Ezzat, et al., 2022).…”

“…The mechanistic analyses of the proapoptotic actions of SOTA compound also showed that it elevated P53 and the BAX/BCL‐2 ratio illustration, which increased active caspase 3/7 rates and promoted apoptosis. Also, it exhibited significant dual inhibition of the topoisomerase IIβ enzyme and β‐tubulin polymerization (Mohammed et al., 2022).…”

Novel 1,3-Thiazole Analogues with Potent Activity against Breast Cancer: A Design, Synthesis, In Vitro, and In Silico Study

“…Molecular modeling studies provide a valuable view of ligand–receptor binding and propose the mode of action of bioactive compounds. The biological activities of chemical compounds are attributed to the binding with key amino acids of the active site of cellular target proteins [ 35 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ]. To elucidate the mechanism by which the synthesized compounds conjugate with VEGFR2 activity, a molecular docking tool was used to examine the interactions of the compounds 3c and 4 toward VEGFR2.…”

“…Draw tool was used to construct the structure of the target compounds 3c and 4 . Then, the protonated 3D structure of target ligands 3c and 4 , the preparation of VEGFR2, and the docking studies were performed using MOE software as previously reported [ 35 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 ]. The validity of the applied protocol was evaluated by performing a molecular docking of the original inhibitor to affirm the main interactions that exist in the reported crystal structure.…”