SYNTHESIS OF MANNISH BASES OF THIOSEMICARBAZIDE AS DNA POLYMERASE INHIBITORS AND NOVEL ANTIBACTERIAL AGENTS

Abstract

Synthesis of new antimicrobial compounds is need of the hour due to prevalence of resistance to antibacterial agents. Different pharmacological activities like, anticancer, antimicrobial, antifungal, anticonvulsant, antimalarial, analgesic and anti-inflammatory are shown by mannich bases and thiosemicarbazide individually. Synthesis of mannich bases was done using aldehyde, ketones and amines having aliphatic, aromatic, cyclic and heterocyclic nature. Synthesized mannich bases were condensed with thiosemicarbazide to form noval mannich bases of thiosemicarbazide as mutual pro-drugs. Spectral analysis was done using IR and H-NMR. Docking analysis performed on the DNA polymerase enzyme (PDB ID 2v4q) showed strong hydrophobic interaction between carbon atom of ketone and amino acids phenylalanine, tyrosine and threonine, charged interactions with aspartine and Vanderwall’s interactions with phenylalanine, aspartine, lysine alanine and threonine, In vitro testing was done using BHI( brain heart infusion)  broth  dilution method against S. aureus (ATCC- 10231) and E. Coli (ATCC-16404). Analogs with aromatic and substituted aromatic aldehyde showed least activity, analogs with aliphatic aldehyde, ketones and amines showed greater activity in Staphylococcus aureus compared to Escherichia Coli. Analogs having morpholine as amine showed comparable activity in both. Compounds K_17, K_18, K_19, K₂₀  have shown comparable highest activity.