Parasitic infections, caused mainly by the species Trichinella spiralis (T. spiralis), are widespread around the world and lead to morbidity and mortality in the population. Meanwhile, some studies have showed that these parasites induce oxidative stress in the infected host. With the aim of developing a class of compounds combining anthelmintic with antioxidant properties, a series of new benzimidazolyl-2-hydrazones 5a-l, bearing hydroxyl- and methoxy-groups, were synthesized. The anthelmintic activity on encapsulated T. spiralis was studied in vitro thus indicating that all hydrazones were more active than the clinically used anthelmintic drugs albendazole and ivermectin. 5b and 5d killed the total parasitic larvae (100% effectiveness) after 24 hours incubation period at 37 °C in both concentrations (50 and 100 μg ml⁻¹). The antioxidant activity of the target compounds was elucidated in vitro against stable free radicals DPPH and ABTS as well as iron induced oxidative damage in model systems containing biologically relevant molecules lecithin and deoxyribose. The two 2,3- and 3,4-dihydroxy hydrazones 5b and 5d were the most effective radical scavengers in all studied systems. DFT calculations were applied to calculate the reaction enthalpies in polar and nonpolar medium and estimate the preferred mechanism of antioxidant activity. The relative radical scavenging ability of compounds 5a-l showed a good correlation to the experimentally observed trends. It was found that the studied compounds are capable to react with various free radicals – ˙OCH₃, ˙OOH and ˙OOCH₃, through several possible reaction pathways – HAT in nonpolar medium, SPLET in polar medium and RAF in both media.

Summary: Conservative treatment of human hydatidosis (cystic echinococcosis) with albendazole has improved significantly the prognosis of the disease. But its therapeutic effectiveness is 30 – 70 %. There is some evidence that the effectiveness of albendazole can be enhanced by praziquantel but there is no strict recommendation for the use of praziquantel as part of long-term drug therapy for hydatidosis. The aim of the study was to evaluate the effectiveness of the combination of albendazole and praziquantel in patients with hepatic and/or pulmonary hydatidosis. A total of 20 patients (aged 12 – 70 years old) were included in the study for a 5-year period. Fourteen patients (70 %) were with hepatic hydatidosis, 4 (20 %) with pulmonary and 2 (10 %) with hepatic and pulmonary hydatidosis. They were treated with albendazole (15 mg/kg/day) and praziquantel (40 mg/kg/weekly) for 2 – 9 one-month courses. The result of the therapy was followed using imaging (abdominal ultrasound, lung radiography, computed tomography) and serology. Seventeen (85 %) out of 20 patients showed evidence of response on imaging defined as improvement or cure of hydatid cysts. Seven (35 %) of the patients with multiple cystic echinococcosis took praziquantel once a week for 6 months. Only 3 patients (15 %) with multiple hydatidosis (2 with liver and 1 with pulmonary hydatidosis) failed to respond to the therapy with both drugs. No side effects have been reported by the patients. The combination of albendazole and praziquantel seems to be an option to improve the therapeutic effectiveness of the conservative treatment of cystic echinococcosis.

Here we presented the synthesis of two groups of heterocyclic benzimidazole derivatives—methanimines 4a–c and hydrazones 6a–c. In vitro biological activity screening of the compounds was performed on isolated encapsulated muscle larvae of Trichinella spiralis. All tested compounds showed higher efficacy than albendazole, with compound 4a demonstrating activity comparable to ivermectin. Structure–activity relationship (SAR) analysis revealed that methanimines 4a–c, containing a thiophene moiety, were more effective than their hydrazone counterparts, highlighting the beneficial synergy between benzimidazole and thiophene pharmacophores. However, replacing the -N=CH- linker in compound 4a with -NH-N=CH- (as in compound 6a) led to a 23% reduction in activity, suggesting that methaniamines possess superior larvicidal potency under equivalent structural conditions. The ability of the studied compounds to interfere with the tubulin polymerization was studied spectrophotometrically on purified porcine brain. Of note, the tested benzimidazoles 4a–b and 6a–b had no discernible effect on tubulin polymerization. An in silico study of the physicochemical and pharmacokinetic characteristics of the novel synthesized heterocyclic benzimidazoles showed that they were characterized by a significant degree of drug-likeness and optimal properties for antineurotrichinellosis agents.

Summary: Dirofilariasis is a zoonotic infection that humans acquire by the bite of infected mosquitoes. The male reproductive system is relatively rare affected by this disease. We presented a case of dirofilariasis of the scrotum from Bulgaria. The patient noticed a small painless nodule in his scrotum with no other pathological findings. The tumor-like lesion was surgically removed. Dirofilariasis was not suspected before this procedure, but the diagnosis was made on histological examination of the extracted tissue. Surgical removal of the helminth is the radical treatment of this disease. Dirofilariasis of the scrotum has a good prognosis as patients fully recover after the extraction of the parasite.