Abstract / Summary
A focused series of four carprofen-derived carbazole-acylthiourea N-(arylcarbamothioyl)propanamides (1a-d) was synthesized by in situ generation of 2-(6-chloro-9H-carbazol-2-yl)propanoyl isothiocyanate followed by reaction with aniline, para-toluidine, para-bromoaniline, and para-iodoaniline, respectively. The structures were supported by FT-IR, NMR, and APCI-HRMS analyses. The compounds were evaluated against clinically relevant bacterial and fungal strains, complemented by antioxidant assays, hemocompatibility/antihemolysis models, cancer cell viability assays, and in silico drug-likeness, pharmacokinetic, pharmacogenomic, and toxicity prediction. The biological profile was substituent-dependent: 1b showed the strongest activity against Staphylococcus aureus (MIC = 0.25 mg/mL), 1a and 1c were the most active against Enterococcus faecalis (MIC = 0.31 mg/mL), while the iodophenyl derivative 1d was the most potent against Candida albicans (MIC = 0.16 mg/mL). Compounds 1b and 1c also inhibited microbial adherence in selected Gram-positive and fungal models. Compound 1a displayed the most consistent antioxidant activity across antioxidant assays and protected erythrocytes from AAPH-induced oxidative hemolysis. The cytotoxicity screening revealed increased sensitivity of A-431 cells, particularly to 1b (IC50 = 13.67 µg/mL). Molecular docking revealed key binding interactions potentially underlying the observed biological activity. Overall, the integrated data identify carbazole-acylthiourea propanamides, especially 1a and 1b, as promising bioactive scaffolds for further optimization as multifunctional compounds.