Synthesis, Characterization, Anticancer, Antioxidant, and In Silico Evaluation of Semicarbazides and Thiosemicarbazides
Anam Shahzadi, Nighat Fatima, Sohail Anjum Shahzad, Amara Mumtaz, Tariq Ismail, Arsalan Ahmed, Aneela Javed, Syed Sajid Hussain Shah, Shamsul Islam
Abstract
High Resolution Image Download MS PowerPoint Slide 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 IC 50 values of 12.6 and 13.7 μg/mL, respectively. Nevertheless, among thiosemicarbazides, 5d and 5b showed notable IC 50 values of 13.0 and 14.6 μg/mL, respectively, against U87 cells. In the antioxidant assay, 4c and 4d showed significant % scavenging with IC 50 values of 4.5 and 7.2 μg/mL, respectively, while 5d and 5b showed IC 50 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.