Quinolones: novel probes in antifilarial chemotheraphy

Quinolones have been discovered in our laboratory as a new class of antifilarial agents. This has led to the design, synthesis, and antifilarial evaluation of a number of N-substituted quinol-4(1H)-one-3-carboxamide derivatives 4-6. The macrofilaricidal activity of the target compounds was initially evaluated in vivo against Acanthoeilonema viteae by oral administration of 200 mg/kg x 5 days. Among all the synthesized compounds, 13 displayed activity, with the most potent compound (4a) exhibiting 100% macrofilaricidal and 90% microfilaricidal activities. Compound 4e elicited significant macrofilaricidal (80%) response while compound 5c showed 100% sterilization of female worms. Finally, the two most potent macrofilaricidal compounds, namely 4a and 4e, have been screened for their potency against DNA topoisomerase II, and it has been observed that both have the capability to interfere with this enzyme at 10 micromol/mL concentration. The structure-activity relationship (SAR) associated with position-3 and aryl ring substituents is discussed.