Evaluation of antitumor potential of novel semicarbazide-based derivatives: cytotoxicity, angiogenesis modulation, and cell cycle effects in in vitro and in vivo models

PURPOSE: Previous studies demonstrated that semicarbazide derivatives 1-(2-chlorophenylcarbonyl)-4-(2,4-dichlorophenyl)semicarbazide (AW8) and 1-(2-chlorophenylcarbonyl)-4-(3,4-dichlorophenyl)semicarbazide (AW12) possess promising physicochemical and anticancer properties. The present study aimed to evaluate their cytotoxicity, selectivity, and angiogenesis-modulating potential using in vitro models and zebrafish, together with an analysis of compound-induced biochemical changes. MATERIALS AND METHODS: The in vitro studies included MTT assay on selected cell lines and an assessment of changes in cell biochemistry using FTIR spectroscopy. Acute toxicity (FET test) and assessment of malformations and cardiotoxicity were also evaluated in a zebrafish model. Human Umbilical Vein Endothelial Cells (HUVEC) cell line and zebrafish Tg(fli1:EGFP) were used to evaluate angiogenesis. RESULTS: = 6453.841; AW8 was not determined), with defects mainly in the yolk sac, pericardium, and spine. Only AW12 significantly influenced angiogenesis in vitro. Therefore, AW12 was selected for in vivo angiogenesis studies, in which >70% of larvae exposed at 4 hpf showed impaired development of dorsal longitudinal anastomotic vessels and intersegmental vessels at the highest doses. CONCLUSION: AW8 and AW12 exhibit selective anticancer activity, particularly against LN229 cells. While both affect apoptosis and necrosis, only AW12 modulates angiogenesis. Notably, AW8 showed a more favorable toxicity profile in vivo, supporting further development of these compounds as potential anticancer agents.