Nirusha K, Nagendra Prasad H S, Lohith T N, Saravanan P, Mallesha L, Anand A P
Department of Chemistry, Sri Jayachamarajendra College of Engineering, JSS Science and Technology University, Mysuru, Karnataka, 570 006, India.
Department of Physics, The National Institute of Engineering, Mysuru, Karnataka, 570008, India.
Arch Microbiol. 2025 Feb 12;207(3):56. doi: 10.1007/s00203-025-04260-z.
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 (H NMR), carbon-nuclear magnetic resonance (C 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.
本研究涉及使用多种光谱方法合成和表征哌嗪 - 柠檬醛磺酰基衍生物5（a - e），这些方法包括傅里叶变换红外光谱（FT - IR）、质子核磁共振（H NMR）、碳核磁共振（C NMR）和液相色谱 - 质谱联用（LC - MS）。为了获得所有哌嗪 - 柠檬醛磺酰基衍生物的能量和其他量子化学计算结果，对以下方法进行了评估：密度泛函理论（DFT）；血脑屏障（BBB）；吸收、分布、代谢和排泄（ADME）；以及计算筛选活性谱预测（PASS），以探讨它们在生物应用中的潜在方法。对合成的化合物进行了类药性、总表面积、极性表面积、氢受体和氢供体参数、clogP和clogS以及其他物理化学特征的检测。哌嗪核心与磺酰基部分的重大重新设计促使在所得化合物中寻找新型抗菌候选物，以对抗耐甲氧西林金黄色葡萄球菌（MRSA）超级细菌。评估了5（a - e）部分对MRSA的抗菌效果。5c部分的抑菌圈直径为15.08±0.05毫米，最低抑菌浓度为29微摩尔，低于链霉素的最低抑菌浓度值17微摩尔（抑菌圈直径为18.16±0.08毫米）。对MRSA的蛋白质3SRW进行的计算机模拟对接研究证实，其杀菌特性对MRSA有效。收集到的研究结果非常明显地表明，5c具有显著更高的对接分数和更强的结合亲和力。为了验证抗菌活性，采用了扫描电子显微镜（SEM）、钾离子外流、细胞渗漏以及对电子传递链的抑制作用。使用人胚肾293细胞系评估5c类似物的细胞毒性，并且其在止血情况下的行为已得到充分证实。根据所获得的数据，作为一种针对MRSA的潜在抗菌竞争者，5c类似物有可能成为一种前沿药物，用于彻底根除MRSA感染。
