Synthesis and In Vitro Biological Studies of Heterocyclic Benzimidazole Derivatives as Potential Therapeutics for Trichinellosis
Year: 2025
Type: article
Abstract: 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.
Source: Applied Sciences
DOI: 10.3390/app15126758
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,896
OpenAlex ID: W4411338405