Sharma Nidhi, Singh Arti, Sharma Ruchika, Kumar Anoop
Department of Pharmacology, ISF College of Pharmacy (ISFCP), Moga, Punjab, India.
Microbiology lab facility, ISF College of Pharmacy (ISFCP), Moga, Punjab, India.
Curr Comput Aided Drug Des. 2021;17(5):687-701. doi: 10.2174/1386207323666200717155640.
The aim of the study was to find out the role of auranofin as a promising broadspectrum antibacterial agent.
In vitro assays (Percentage growth retardation, Bacterial growth kinetics, Biofilm formation assay) and In silico study (Molegro virtual docker (MVD) version 6.0 and Molecular operating environment (MOE) version 2008.10 software).
The in vitro assays have shown that auranofin has good antibacterial activity against Gram positive and Gram negative bacterial strains. Further, auranofin has shown synergistic activity in combination with ampicillin against S. aureus and B. subtilis whereas in combination with neomycin has just shown additive effect against E. coli, P. aeruginosa and B. pumilus. In vivo results have revealed that auranofin alone and in combination with standard drugs significantly decreased the bioburden in the zebrafish infection model as compared to control. The molecular docking study have shown good interaction of auranofin with penicillin-binding protein (2Y2M), topoisomerase (3TTZ), UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosaminedeacetylase (3UHM), cell adhesion protein (4QRK), β-lactamase (5CTN) and arylsulphatase (1HDH) enzyme as that of reference ligand which indicate the multimodal mechanism of action of auranofin. Finally, MTT assay has shown the non-cytotoxic effect of auranofin.
In conclusion, auranofin in combination with existing antibiotics, could be developed as a broad spectrum antibacterial agent; however, further studies are required to confirm its safety and efficacy. This study provides the possibility of the use of auranofin apart from its established therapeutic indication in combination with existing antibiotics to tackle the problem of resistance.
本研究旨在探究金诺芬作为一种有前景的广谱抗菌剂的作用。
体外试验（生长抑制百分比、细菌生长动力学、生物膜形成试验）和计算机模拟研究（Molegro虚拟对接软件（MVD）6.0版本和分子操作环境软件（MOE）2008.10版本）。
体外试验表明，金诺芬对革兰氏阳性和革兰氏阴性菌株均具有良好的抗菌活性。此外，金诺芬与氨苄西林联合使用时，对金黄色葡萄球菌和枯草芽孢杆菌表现出协同活性，而与新霉素联合使用时，对大肠杆菌、铜绿假单胞菌和短小芽孢杆菌仅表现出相加作用。体内结果显示，与对照组相比，单独使用金诺芬以及与标准药物联合使用均能显著降低斑马鱼感染模型中的生物负荷。分子对接研究表明，金诺芬与青霉素结合蛋白（2Y2M）、拓扑异构酶（3TTZ）、UDP-3-O-[3-羟基肉豆蔻酰基]N-乙酰葡糖胺脱乙酰酶（3UHM）、细胞粘附蛋白（4QRK）、β-内酰胺酶（5CTN）和芳基硫酸酯酶（1HDH）的相互作用与参考配体相似，这表明金诺芬具有多模式作用机制。最后，MTT试验表明金诺芬无细胞毒性作用。
总之，金诺芬与现有抗生素联合使用可开发为广谱抗菌剂；然而，需要进一步研究以确认其安全性和有效性。本研究为金诺芬除其既定治疗适应症外，与现有抗生素联合使用以解决耐药性问题提供了可能性。
