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现有药物用于细菌感染的重新利用:一项计算机模拟和体外研究。

Repurposing of Existing Drugs for the Bacterial Infections: An In silico and In vitro Study.

作者信息

Kapoor Yachika, Sharma Ruchika, Kumar Anoop

机构信息

Department of Biotechnology, ISF Institute of Professional Studies (ISFIPS), Moga, Punjab, India.

Department of Pharmacology, ISF College of Pharmacy (ISFCP), Moga, Punjab, India.

出版信息

Infect Disord Drug Targets. 2020;20(2):182-197. doi: 10.2174/1871526519666181126094244.

Abstract

BACKGROUND

The emergence of infectious diseases and its resistance to approved drugs is a global threat to human health. The incidence of infectious diseases is increasing day by day and expected to rise exponentially in next 2 decades. Thus, there is a need for new treatment modalities for the treatment of microbial infections.

METHODS

Thus, in the current investigation, we have explored the existing drugs [metformin (Anti-diabetic), propranolol (Anti-hypertensive) and amitriptyline (antidepressant)] for treatment of infectious diseases.

RESULTS

An in-silico result of current investigation has shown the good interaction of metformin, propranolol, and amitriptyline towards various targets (Beta-lactamase, Penicillin-binding proteins, Staphylokinase protein, Oxidoreductase protein, etc.) of gram positive and gram negative bacteria as that of internal ligand. Further, in-vitro results have shown that the antibacterial activity of metformin, propranolol, and amitriptyline against Bacillus pumilus, Pseudomonas aeruginosa and Staphylococcus aureus.

CONCLUSION

The parameters such as Microtiter assay: percentage growth retardation and bacterial growth kinetics, Minimum inhibitory concentration (MIC), Post-antibiotic assay and Biofilm formation have indicated the antibacterial potential of metformin, propranolol, and amitriptyline. However, before starting a clinical trial, complete safety and efficacy profile of drugs in the treatment of infectious diseases should be investigated.

摘要

背景

传染病的出现及其对已批准药物的耐药性是对人类健康的全球威胁。传染病的发病率日益上升,预计在未来20年将呈指数级增长。因此,需要新的治疗方式来治疗微生物感染。

方法

因此,在当前的研究中,我们探索了现有药物[二甲双胍(抗糖尿病药)、普萘洛尔(抗高血压药)和阿米替林(抗抑郁药)]用于治疗传染病。

结果

当前研究的计算机模拟结果显示,二甲双胍、普萘洛尔和阿米替林与革兰氏阳性和革兰氏阴性细菌的各种靶点(β-内酰胺酶、青霉素结合蛋白、葡萄激酶蛋白、氧化还原酶蛋白等)具有良好的相互作用,与内源性配体相当。此外,体外结果表明,二甲双胍、普萘洛尔和阿米替林对短小芽孢杆菌、铜绿假单胞菌和金黄色葡萄球菌具有抗菌活性。

结论

微量滴定试验参数(生长抑制百分比和细菌生长动力学)、最低抑菌浓度(MIC)、抗生素后效应试验和生物膜形成表明了二甲双胍、普萘洛尔和阿米替林的抗菌潜力。然而,在开始临床试验之前,应研究药物在治疗传染病方面的完整安全性和有效性。

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