Design and synthesis of aminothiazole-benzazole based amide: antiproliferative, antimigration activity and molecular docking studies


Karahan G. A., ERZURUMLU Y., MUHAMMED M. T., ÖZÇELİK A. B.

MEDICINAL CHEMISTRY RESEARCH, 2024 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2024
  • Doi Number: 10.1007/s00044-024-03344-7
  • Journal Name: MEDICINAL CHEMISTRY RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, Veterinary Science Database
  • Gazi University Affiliated: Yes

Abstract

In this study, we synthesized a series of amide-functionalized aminothiazole-benzazole analogs for potential application in cancer treatment. The chemical structures of these compounds were confirmed using proton nuclear magnetic resonance (1H NMR), carbon-13 nuclear magnetic resonance (13C NMR) spectroscopy, and high-resolution mass spectrometry (HRMS). We evaluated the cytotoxicity of these compounds against breast cancer cells (MCF-7) and lung adenocarcinoma cells (A549). Notably, Compound 6b demonstrated significant cytotoxicity, with IC50 values of 17.2 +/- 1.9 mu M for MCF-7 cells and 19.0 +/- 3.2 mu M for A549 cells. Furthermore, we assessed the antimigration properties of all synthesized compounds, observing promising antiproliferative effects in both MCF-7 and A549 cells. Compound 6b exhibited a significant antimigration effect, achieving a 50.2 +/- 4.7% wound healing rate in MCF-7 cells. In addition, we examined the impact of these compounds on key apoptotic proteins, including Caspase-7, PARP-1, BAX, and Bcl-2, which are critical in the regulation of programmed cell death. The binding potentials of the active compounds to BAX and Bcl-2 were also supported by docking. Results that consolidate the in vitro study were obtained from the in silico analysis. Our results suggest that these amide-functionalized aminothiazole-benzazole analogs exhibit potential as anticancer agents and merit further investigation to elucidate their mechanisms of action and therapeutic potential.Graphical abstractThe synthesis of novel aminothiazole-benzazole-based amide derivatives as potential anticancer agents has been reported. These compounds were evaluated for their cytotoxic activity against MCF-7 and A549 cancer cell lines, exhibiting IC50 values ranging from 17.2 to 80.6 mu M. Furthermore, the cytotoxic compounds demonstrated significant antimigration effects and induced apoptosis in both MCF-7 and A549 cell lines. Additionally, the results confirming the in vitro study were supported by in silico analysis.