In Vitro Macrofilaricidal and Microfilaricidal Activities against Onchocerca ochengi, Cytotoxicity and Acute Toxicity of Seventeen Thiazolidinone Derivatives

Abstract

In the search for suitable drugs for onchocerciasis, 17 synthetic thiazolidinone derivatives (TZDs) were screened for activity against the worm stages of Onchocerca ochengi, which cause the disease and the safety of the most active compounds was also assessed. Anti-onchocerca activity was assessed against the adult worms and microfilariae isolated from cattle skin, using worm motility and MTT formazan reduction assays. The cytotoxicity of the most active compounds was assessed on LLCMK2 (monkey kidney epithelial) cells and acute toxicity was assessed in BALB/c mice. Of the 17 TZDs, 8 and 4 compounds were highly active against adult male (AM) and adult female (AF) worms, respectively (≥90% inhibition, IC50 3 was the most active (IC50 = 0.098 µM) against AM; compound 5 was the most active (IC50 = 0.302 µM) against AF and 16 was the most selective (SI = 607.5). Sixteen compounds were active against microfilariae and 9 showed high activity against all three worm stages. No mortality, no adverse effects and no significant changes in liver and kidney functions were observed in acute toxicity test of the most active compounds in mice (p < 0.05). Some thiazolidinone derivatives demonstrated high macrofilaricidal and microfilaricidal activities at micromolar potency, high selectivity, no cytotoxicity and no adverse effects in mice. These broad-acting compounds have the potential for use in the eradication of onchocerciasis. Further studies should be pursued towards lead characterization.