Exploration of piperazine-citral sulfonyl derivatives: antibacterial and in-silico studies against methicillin-resistant Staphylococcus aureus

Abstract

This study involved the synthesis and characterization of piperazine-citral sulfonyl derivatives 5(a-e) using a variety of spectrum methods, including fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (¹H NMR), carbon-nuclear magnetic resonance (¹³C NMR), and liquid chromatography mass spectroscopy (LC–MS). To obtain the energy and other quantum chemical computations of all the piperazine-citral sulfonyl derivatives, the following methods were evaluated: density functional theory (DFT); blood brain barrier (BBB); absorption, distribution, metabolism, and excretion (ADME); and prediction of activity spectra of computational screening (PASS) for their potential approaches for biological applications. The synthesized compounds were examined for drug-likeness, total surface area, polar surface area, H-acceptor and H-donor parameters, clogP and clogS, and other physicochemical features. The significant redesign of the piperazine core with the sulfonyl moiety encourages the search for novel antibacterial candidates among the resulting compounds to combat Methicillin-resistant Staphylococcus aureus (MRSA) superbugs. The antibacterial efficacy of 5(a–e) moieties against MRSA was evaluated. The 5c moiety shows a value of 29 µM and 15.08 ± 0.05 zone of inhibition (ZOI) in mm, which is lower than the minimum inhibitory concentration (MIC) value of streptomycin, which is 17 μM (18.16 ± 0.08) ZOI in mm). An in-silico docking study on the protein 3SRW of MRSA confirmed that the biocidal properties were effective against MRSA. The findings that were gathered made it very evident that 5c had a significantly greater docking score, and a stronger binding affinity. To verify the antibacterial activity, SEM, potassium efflux, cellular leakage, and an inhibitory effect on the electron transport chain were employed. HEK 293 cell lines were used to evaluate the 5c analogue’s cytotoxicity, and its behaviour under haemostatic circumstances was well-established. As a prospective antibacterial competitor against MRSA, 5c analogue has the potential to be a cutting-edge medication for the complete eradication of MRSA infections, according to the data obtained.