Synthesis, Characterization, Anticancer, Antioxidant, and In Silico Evaluation of Semicarbazides and...

This study aims to synthesize semicarbazides and thiosemicarbazides and evaluate them for their biological potential. In the current study, the hydrazide was used as a precursor for the synthesis of semicarbazides (4a-c) and thiosemicarbazides (5a-f). The synthesized compounds were evaluated for their anticancer activity against neuroblastoma cells (IMR-32), malignant glioma cells (U87), and fibroblasts (NIH3T3) and antioxidant potential. Nitro-substituted semicarbazides 4c and 4d showed remarkable anticancer effects against the U87 cell line, with IC₅₀ values of 12.6 and 13.7 μg/mL, respectively. Nevertheless, among thiosemicarbazides, 5d and 5b showed notable IC₅₀ values of 13.0 and 14.6 μg/mL, respectively, against U87 cells. In the antioxidant assay, 4c and 4d showed significant % scavenging with IC₅₀ values of 4.5 and 7.2 μg/mL, respectively, while 5d and 5b showed IC₅₀ values of 5.6 and 7.0 μg/mL, respectively. Docking studies revealed that 4c, 4d, and 5d showed significant binding with the ATP-dependent enzyme topoisomerase II (IZXN) target, with binding energies of -8.1, -7.9, and -7.3 kcal/mol, respectively. ADME analysis indicated that these compounds possess substantial GIT absorption and moderate BBB penetration. These findings showed that synthesized compounds can be used as drug leads based on their anticancer, antioxidant, and in silico properties.