SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL SCREENING OF NOVEL THIOSEMICARBAZONES AND THEIR DERIVATIVES WITH MOLECULAR DOCKING STUDIES TO EXPLORE ANTI-MICROBIAL AND ANTI-DIABETIC POTENTIAL

Abstract

Background: Thiosemicarbazones (TSCs) are an important class of organosulfur compounds known for diverse biological activities, including antimicrobial, antiviral, anticancer, and enzyme-inhibitory effects. Their pharmacological potential arises from strong metal-chelating ability and flexible functionalization on the imine-thione framework. Owing to the growing prevalence of antimicrobial resistance and diabetes, the development of multifunctional therapeutic scaffolds such as TSCs has gained renewed scientific interest.

Objective: This study aimed to synthesize, characterize, and evaluate two novel naphthalene-based thiosemicarbazone derivatives—WS-1 and WS-2—for their antimicrobial and antidiabetic potential, supported by molecular docking and in silico pharmacological profiling.

Methods: WS-1 and WS-2 were synthesized through an acid-catalyzed condensation between thiosemicarbazide and either 1,5,7-trichloronaphthalene-2-carbaldehyde or 1,5,7-trihydroxynaphthalene-2-carbaldehyde, yielding 80% for each compound. Structural confirmation was achieved via UV-Vis and FT-IR spectroscopy. Antibacterial activity was tested against Bacillus subtilis (Gram-positive) and Escherichia coli (Gram-negative) using the agar disc diffusion method at concentrations up to 30 mg/mL. The antidiabetic activity was assessed by α-glucosidase inhibition assay at 50 µg/mL, using acarbose as a reference. Molecular docking was performed to explore interactions with α-glucosidase and bacterial target proteins, supported by in silico ADMET profiling.

Results: Both compounds exhibited high structural purity and stability. WS-1 produced inhibition zones of 26 mm against B. subtilis and 24 mm against E. coli, while WS-2 showed moderate zones of 17 mm and 11 mm, respectively. In α-glucosidase assays, WS-2 inhibited 22.54% and WS-1 inhibited 11.44% compared with 40.38% for acarbose. Docking results demonstrated strong binding energies of −8.1 kJ/mol (WS-1) and −8.3 kJ/mol (WS-2) with key hydrogen and halogen interactions at the enzyme’s active site.

Conclusion: The integrated experimental and computational findings confirm that WS-1 and WS-2 possess dual antimicrobial and antidiabetic activity. Their structural simplicity, stability, and drug-like in silico properties highlight these molecules as promising lead scaffolds for developing future multifunctional therapeutics.