SYNTHESIS AND ANTI-TRICHINELLA SPIRALIS ACTIVITY IN VITRO OF SOME NEW 1H-BENZIMIDAZOLES

Novel derivatives of 1H-benzimidazole which combine into a single molecule two pharmacophores – the benzimidazole and piperazine rings possessing antihelmintic activity have been synthesized. Their structures were confirmed by IR, 1H NMR, 13C NMR and elemental analysis techniques.The compounds exhibited remarkable effect on the viability of isolated Trichinella spiralis muscle larvae in in vitro model at a dose of 100 μg/ml after 24 h. The results obtained by the hepatotoxicity test showed that compound 4 had the lowest hepatotoxity.Novel derivatives of 1H-benzimidazole which combine into a single molecule two pharmacophores – the benzimidazole and piperazine rings possessing antihelmintic activity have been synthesized. Their structures were confirmed by IR, 1H NMR, 13C NMR and elemental analysis techniques.The compounds exhibited remarkable effect on the viability of isolated Trichinella spiralis muscle larvae in in vitro model at a dose of 100 μg/ml after 24 h. The results obtained by the hepatotoxicity test showed that compound 4 had the lowest hepatotoxity

A Comprehensive Evaluation of Sdox, a Promising H2S-Releasing Doxorubicin for the Treatment of Chemoresistant Tumors

Sdox is a hydrogen sulfide (H2S)-releasing doxorubicin effective in P-glycoprotein-overexpressing/doxorubicin-resistant tumor models and not cytotoxic, as the parental drug, in H9c2 cardiomyocytes. The aim of this study was the assessment of Sdox drug-like features and its absorption, distribution, metabolism, and excretion (ADME)/toxicity properties, by a multi- and transdisciplinary in silico, in vitro, and in vivo approach. Doxorubicin was used as the reference compound. The in silico profiling suggested that Sdox possesses higher lipophilicity and lower solubility compared to doxorubicin, and the off-targets prediction revealed relevant differences between Dox and Sdox towards several cancer targets, suggesting different toxicological profiles. In vitro data showed that Sdox is a substrate with lower affinity for P-glycoprotein, less hepatotoxic, and causes less oxidative damage than doxorubicin. Both anthracyclines inhibited CYP3A4, but not hERG currents. Unlike doxorubicin, the percentage of zebrafish live embryos at 72 hpf was not affected by Sdox treatment. In conclusion, these findings demonstrate that Sdox displays a more favorable drug-like ADME/toxicity profile than doxorubicin, different selectivity towards cancer targets, along with a greater preclinical efficacy in resistant tumors. Therefore, Sdox represents a prototype of innovative anthracyclines, worthy of further investigations in clinical settings