Synthesis of Quinolone-Based Thiadiazoles Targeting Topoisomerase II for Cancer Chemotherapy

Background: Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. Fluoroquinolones have been reported to decrease tumor growth and DNA synthesis resulting in S- and G2/M-phase cell cycle arrest. This type of antibiotics induce cell apoptosis by causing mitochondrial dysfunction in lung, bone, bladder, and prostate cancer cells. Levofloxacin (LV) is a fluoroquinolone antimicrobial agent which acts through inhibiting bacterial DNA gyrase and topoisomerase IV. In this work, promising initial results in the C-3 modification of levofloxacin have been considered to change its cytotoxic activity. Material and methods: The design concept involved modification of the C-3 carboxylic acid in fluoroquinolones with 5-amino-1,3,4-thiadiazole-2-thiole derivatives as amine group to obtain related carboxamide. The synthetic work employed in this study provides a good example for the synthesis of pure 1,3,4-thiadiazole based fluoroquinolones. Results: In order to prepare of carboxamide derivatives of levofloxacin was used ethyl chloroformate reagent and 5-amino-1,3,4-thiadiazole-2-thiole analogous in dichloromethane, provided the corresponding levofloxacin based thiadiazole 1a-m in moderate yields. Conclusions: The synthesized compounds were stablished by means of 1HNMR and mass spectroscopy. Considering pharmacophore of quinolone-based thiadiazole derivatives could be entered in vitro tests for anticancer efficacy.

کلیدواژه ها:

Cancer ، Fluoroquinolones ، Synthesis ، Thiadiazole ، Topoisomerase II.