Design, Synthesis and Pharmacological Evaluation of Sulfanilamide-Ciprofloxacin Conjugates Utilizing Hybridization Approach as New Antibacterial Agents

摘要

A group of novel antibacterial agents (I-V) were designed and synthesized, by utilizing hybridization approach between ciprofloxacin and sulfanilamide, through metabolically stable linkers, to be acted by dual mode of actions. Ciprofloxacin acts by inhibition of topoisomerase enzyme, which is necessary for DNA replication, while sulfonamides act through inhibition of carbonic anhydrase enzyme, which is necessary for bacterial metabolic activity. Anti-tuberculosis activity of these compounds was evaluated on MDR Mycobacterium tuberculosis (resist to rifampicin and INH), in a dose equivalent to (10 mg/ 5 ml D.W.) of ciprofloxacin. Compounds II, III showed non-significant reduction in the number of bacterial colonies (bacterial growth) with respect to the effect of ciprofloxacin (standard), compound IV produce a significant reduction in the number of bacterial colonies in comparable to ciprofloxacin. Moreover, compounds I and V exhibited highly significant reduction in the number of bacterial colonies compared to ciprofloxacin. The results of this study indicate that the hybridization approach between the ciprofloxacin and sulfanilamide will give superior anti-tubercular activity in comparison to ciprofloxacin, when they are linked through amide linkage directly or through incorporation of thiadiazol and triazole derivatives through disulfide bond. This will encourage further evaluation of these compounds to demonstrate or identify their selectivity toward ?-CA enzyme. Keywords: Anti-tuberculosis activity; ciprofloxacin; sulfanilamide; hybridization approach; carbonic anhydrase; and topoisomerase.