Design, synthesis, molecular docking and DFT computational insight on the structure of Piperazine sulfynol derivatives as a new antibacterial contender against superbugs MRSA

• Published in: Journal of molecular structure 2022-01, Vol.1247, p.131333, Article 131333
• Main Authors: Prasad, H. S. Nagendra, Ananda, A.P., Lohith, T.N., Prabhuprasad, P., Jayanth, H.S., Krishnamurthy, N.B., Sridhar, M.A., Mallesha, L., Mallu, P.
• Format: Article
• Language: English
• Subjects: Antibacterial activity; DFT; Molecular docking; MRSA; Piperazine sulfynol derivatives
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2021.131333

•A series of piperazine sulfynol derivatives were synthesized and amply characterized by various spectral techniques viz, LC-MS, 1H NMR, 13C NMR, and FT-IR.•All the piperazine sulfynol derivatives deliberated for pharmacophore model, ADME, DFT, PASS, and BBB analysis.•The potency of synthesized derivatives was evaluated for anti-superbug against MRSA by molecular docking study.•The toxicity has assessed against L6 cell lines.•Bio-compatibility has demonstrated at the hemostatic condition. In this investigation, a series of piperazine sulfynol derivatives 5(a-l) were synthesized and amply characterized by various spectral techniques viz, LC-MS, 1H NMR, 13C NMR, and FT-IR. The energy and other quantum chemical computations of all the piperazine sulfynol derivatives were achieved using Density functional theory (DFT), Absorption, Distribution, Metabolism and Excretion (ADME), Blood Brain Barrier (BBB) and their Prediction of Activity Spectra of Computational Screening (PASS) for their possible approaches for biological applications were evaluated. The synthesized compounds were checked for the physicochemical properties such as clogP, clogS, drug-likeness, total surface area, polar surface area, H-acceptor, and H-donor parameters. The considerable change in the design with sulfonyl moiety on the piperazine core motivates to find out new antibacterial contender of the resultant molecules against superbugs-MRSA. All 5(a-l) moieties were tested for antibacterial potency against MRSA. The 5e moiety shows a MIC value of 35±0.41 µg/mL and 9.90±0.03 ZOI in mm compared to drug bacitracin 10 µg/disk (10.21±0.04) and streptomycin 10 µg/disk (14.10±0.06) ZOI in mm. The action of biocidal properties against MRSA was confirmed by an in silico docking study on the protein 1FZP and 3SRW of MRSA. The revealed data strongly recommended 5e having a good docking score, binding energy, and glide energy with high binding affinity. The antibacterial activity was validated by SEM, cellular leakage, potassium efflux and inhibitory effect on electron transport chain. The behavior of the 5e analog in haemostatic condition was well established and cytotoxicity was evaluated against L6 cell lines. The revealed data showed that 5e analog is a potential antibacterial contender against MRSA and it can be used as a futuristic drug in the eradication of MRSA infections. [Display omitted]