Comparison of ADMET profile between thiosemicarbazide and semicarbazide derivatives regarding anticancer properties.

Introduction: The incidence of cancer is constantly increasing, and current cytostatics are not effective enough and cause serious side effects. Thio/semicarbazide derivatives seem to be promising candidates for anticancer drugs. This systematic review aimed to analyze comparatively the ADMET profiles of thiosemicarbazides and semicarbazides with proven antitumor activity published through August 2024.

Methods: A search of PubMed, ScienceDirect and Google Scholar databases was performed. Qualified compounds were subjected to in silico analysis using ADMETlab 2.0 software. The data were statistically analyzed (Student's t-test, Mann-Whitney U test, Chi²).

Results: Comparative analysis showed that semicarbazides have more favorable intestinal absorption properties and lower biological activity but have higher selectivity of action and lower risk of drug interactions. Thiosemicarbazides have a higher probability of metabolic activity with concomitant increased toxicity. These compounds show significantly higher levels of binding to plasma proteins, a lower average percentage of the unbound fraction, and a longer half-life.

Conclusions: In light of anticancer therapies, thiosemicarbazides can cause increased oxidative stress and DNA damage, which is one strategy for cancer treatment. However, semicarbazides are better candidates for anticancer drug trials because of their better pharmacokinetic and pharmacodynamic profiles and lower toxicity.