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.

Background/Objectives: Cystic echinococcosis (hydatidosis) is a zoonotic parasitic disease primarily managed surgically, yet postoperative recurrences affect 2–22% of patients. Albendazole is standard for prophylaxis, but recurrences still occur. This study evaluated whether combining albendazole with praziquantel improves prevention of postoperative recurrences while assessing tolerability. Methods: This single-centre, retrospective, two-arm cohort study included 60 patients (aged 19–77, mean 43.9 ± 15.1 years) undergoing surgery for hepatic, pulmonary and/or abdominal hydatidosis between April 2024 and April 2026. All patients received albendazole (400 mg twice daily for 2–4 months). Thirty patients additionally received praziquantel (25 mg/kg/day for 10 days) in the first three postoperative months. Follow-up was systematically shorter in the combination arm (median 10 months, range 6–18) versus the albendazole-only arm (median 24 months, range 6–24). Results: Significant baseline imbalances existed between arms (14/15 covariates with |SMD| > 0.10), with the combination group having more abdominal and fertile cysts plus higher baseline transaminases. Of 118 resected cysts, two recurrences (6.7%) occurred in the albendazole arm at 12 months (incidence rate 3.73/100 person-years). No recurrences were observed in the combination arm within its shorter follow-up window. Adverse events were similar (43.3% vs 50.0%; adjusted OR 1.09, 95% CI 0.33–3.57), with no significant added hepatotoxicity after adjustment. Conclusions: Albendazole plus praziquantel was well tolerated. Due to baseline imbalances, differential follow-up, and limited events, these data do not support firm conclusions on superior efficacy. The hypothesis-generating signal warrants confirmation in a prospective, randomized trial with long-term balanced follow-up and optimized dosing.

Background/Objectives: Cystic echinococcosis is primarily managed surgically, yet postoperative recurrence affects 2–22% of patients despite albendazole prophylaxis. This study describes the tolerability of adding praziquantel to postoperative albendazole and reports recurrence signals where efficacy cannot be inferred. Methods: In this single-centre, retrospective, two-arm cohort, 60 patients undergoing hydatid cyst surgery (2024–2026) received albendazole and 30 additionally received praziquantel. The follow-up was substantially shorter in the combination arm (median 10 versus 24 months), and recurrence was first ascertainable only from 12 months, the central limitation. Analyses used standardized mean differences, person time incidence, propensity score and inverse probability weighting, a DAG-based hepatotoxicity model, and a Bayesian Beta-Binomial re-analysis. Results: Baseline covariates were markedly imbalanced (14/15 with |SMD| > 0.10). Two recurrences occurred, both in the albendazole arm (3.73/100 person-years) and none in the combination arm’s shorter window. Adverse events were similar (43.3% vs. 50.0%), with no added hepatotoxicity after adjustment (odds ratio 1.45, 95% CI 0.49–4.37). The Bayesian posterior probability of benefit (0.88–0.93) remained below 0.95, a descriptive signal only. Conclusions: Albendazole plus praziquantel was well tolerated, but severe baseline imbalance, differential follow-up, and only two events mean efficacy cannot be assessed. The results of our study are hypothesis-generating. Further confirmation requires a prospective, multicentre randomized trial with balanced long-term follow-up.