SYNTHESIS AND ANTITUMOR ACTIVITY OF C-3 AMINOTHIAZOLE DERIVATIVES OF FLUOROQUINOLONES

Abstract

Cancer is a complex disease marked by abnormal cell growth. Despite significant progress in cancer treatment, the chemotherapy index is still low due to the emergence of clinical anti-cancer drug resistance and serious side effects, so the search and development of new anti-cancer drugs is still a hot spot in drug research.  Although quinolones are widely used antibacterial drugs in clinical practice, their high activity against eukaryotic topoisomerases and toxicity to tumor cells also highlight their potential as new anticancer drugs. 2-aminothiazole derivatives have a wide range of pharmacological activities. The presence of C-2 amino group not only facilitates the splicing of thiazoles with other active fragments to synthesize compounds with diverse structures, but also increases the hydrophilicity of compounds, improves their water solubility and bioavailability, and enhances the ability to form hydrogen bonds with the target site. Based on the structure and mechanism drug design strategy, 30 C-3 aminothiazole derivatives of fluoroquinolones were designed and synthesized by combining the C-3 position of the parent nucleus of fluoroquinolones with 2-aminothiazole derivatives. It is concluded that the target compound of fluoroquinolone-3-aminothiazoles constructed by combining the quinolone parent nucleus with the structure of 2-aminothiazole shows good anti-tumor activity, which provides a new idea for the further research of anti-tumor fluoroquinolones.