New 5-Aryl-1,3,4-Thiadiazole-Based Anticancer Agents: Design, Synthesis, In Vitro Biological Evaluation and In Vivo Radioactive Tracing Studies

• Main Authors: Rana M. El-Masry (Author), Basma M. Essa (Author), Adli A. Selim (Author), Soad Z. El-Emam (Author), Khaled O. Mohamed (Author), Tamer M. Sakr (Author), Hanan H. Kadry (Author), Azza T. Taher (Author), Sahar M. Abou-Seri (Author)
• Formato: Livro
• Publicado em: MDPI AG, 2022-11-01T00:00:00Z.
• Assuntos: article
• Acesso em linha: Connect to this object online.
• Notes: 10.3390/ph15121476; 1424-8247
• Keywords: 1,3,4-thiadiazole; anticancer activity; structure-activity relationship; radiolabeling; in vivo pharmacokinetics; Medicine; R; Pharmacy and materia medica; RS1-441
• Source: Pharmaceuticals, Vol 15, Iss 12, p 1476 (2022)

A new series of 5-(4-chlorophenyl)-1,3,4-thiadiazole-based compounds featuring pyridinium (<b>3</b>), substituted piperazines (<b>4a-g</b>), benzyl piperidine (<b>4i</b>), and aryl aminothiazoles (<b>5a-e</b>) heterocycles were synthesized. Evaluation of the cytotoxicity potential of the new compounds against MCF-7 and HepG2 cancer cell lines indicated that compounds <b>4e</b> and <b>4i</b> displayed the highest activity toward the tested cancer cells. A selectivity study demonstrated the high selective cytotoxicity of <b>4e</b> and <b>4i</b> towards cancerous cells over normal mammalian Vero cells. Cell cycle analysis revealed that treatment with either compound <b>4e</b> or <b>4i</b> induced cell cycle arrest at the S and G2/M phases in HepG2 and MCF-7 cells, respectively. Moreover, the significant increase in the Bax/Bcl-2 ratio and caspase 9 levels in HepG2 and MCF-7 cells treated with either <b>4e</b> or <b>4i</b> indicated that their cytotoxic effect is attributed to the ability to induce apoptotic cell death. Finally, an in vivo radioactive tracing study of compound <b>4i</b> proved its targeting ability to sarcoma cells in a tumor-bearing mice model.