Antimicrobial Activity of Lapachol-Based Semicarbazones Against Drug-Resistant Bacterial Strains and in Silico ADMET Evaluation

Abstract

Leveraging the antimicrobial potential of both naphthoquinones and semicarbazones, four semicarbazones (SMC1–SMC4) from lapachol with inherent antibacterial potential were designed. For the synthesis of the semicarbazones, a two-step synthetic route was proposed. Initially, lapachol was extracted from the Tabebuia genus tree and subsequently subjected to acid cyclization to yield α-lapachone (2), β-lapachone (3), β-lapachone-3-sulfonic acid (4), and 3-iodo-β-lapachone (5). To synthesize the semicarbazones (SMC1-SMC4), the naphthoquinones reacted with semicarbazide hydrochloride, resulting in products with yields ranging from 30% to 79%. Following this, the antibacterial efficacy of the compounds was evaluated against methicillin-resistant and non-resistant Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii, and Klebsiella pneumoniae. Compounds 3, 4, and SMC4 demonstrated antimicrobial potential against resistant bacterial strains, and with MIC values of 0.03, 0.78 and 1.18 mM, respectively, against methicillin-resistant S. aureus. Naphthoquinone 3 demonstrated antimicrobial potential against susceptible S. aureus, E. coli, A. baumannii, and K. pneumoniae, and MIC values of 0.03, 0.52, 0.52 and 0.52 mM, respectively. Additionally, in silico assays suggested that compounds 3, 4 and SMC4 possess suitable ADMET pharmacokinetic profiles alongside low toxicity.