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

ABSTRACT: 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.

SUBMITTER: Alov P 

PROVIDER: S-EPMC8936434 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature