用于细菌共感染潜在治疗的杂化化合物的设计和合成:体外抗菌和计算机研究。

IF 4.3 2区 医学 Q1 INFECTIOUS DISEASES
Vuyolwethu Khwaza, Opeoluwa O Oyedeji, Eric Morifi, Mutshinyalo Nwamadi, Thierry Youmbi Fonkui, Derek Tantoh Ndinteh, Blessing A Aderibigbe
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引用次数: 0

摘要

背景:由于与COVID-19相关的细菌合并感染的增加,对创新治疗策略以改善患者预后的需求增加。方法:将两种已知的药物支架结合合成10种杂化化合物,以增强抗菌活性和克服耐药机制。合成的化合物对5株革兰氏阴性菌和7株革兰氏阳性菌的抑菌活性进行了评价。使用SwissADME网络工具预测选定的活性化合物(12- 16,19,21和23)的药代动力学和药物相似特性。结果:化合物12-16、19、21和23表现出明显的抑菌活性,其中化合物16(含环丙沙星的杂交种)抑菌效果最强,最低抑菌浓度(MIC)为7.8125µg/mL。计算机分析显示大多数杂化化合物具有良好的药代动力学特征、药物相似性、亲脂性和水溶性。讨论:合成的杂化化合物表现出增强的抗菌活性和理想的药代动力学性质,特别是化合物16。这些发现表明,这些分子在对抗细菌性病原体方面具有潜力,特别是那些与COVID-19感染中合并感染有关的病原体。结论:本研究提出了一种有前景的混合抗菌药物,可作为治疗covid -19相关细菌合并感染的辅助疗法。需要进一步的研究,这可能导致有效的治疗方法来管理病毒性疾病背景下的继发性细菌感染。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Design and Synthesis of Hybrid Compounds for Potential Treatment of Bacterial Co-Infections: In Vitro Antibacterial and In Silico Studies.

Background: The need for innovative therapeutic strategies to enhance patient outcomes has increased due to the rise in bacterial co-infections associated with COVID-19. Methods: In this study, ten hybrid compounds were synthesized by combining two known pharmaceutical scaffolds to enhance antibacterial activity and overcome resistance mechanisms. The synthesized compounds were evaluated for their antibacterial activity against five Gram-negative and seven Gram-positive bacterial strains. In silico pharmacokinetic and drug-likeness properties of selected active compounds (12-16, 19, 21, and 23) were predicted using the SwissADME web tool. Results: Compounds 12-16, 19, 21, and 23 demonstrated significant antibacterial activity, with compound 16 (a ciprofloxacin-containing hybrid) exhibiting the most potent effect, showing a minimum inhibitory concentration (MIC) of 7.8125 µg/mL against all tested bacterial strains. The in silico analysis revealed favorable pharmacokinetic profiles, drug-likeness, lipophilicity, and water solubility of most hybrid compounds. Discussion: The synthesized hybrid compounds exhibited enhanced antibacterial activity and desirable pharmacokinetic properties, particularly compound 16. These findings suggest the potential of these molecules in combating bacterial pathogens, especially those implicated in co-infections in COVID-19 infections. Conclusions: The study presents promising hybrid antibacterial agents with potential application as adjunct therapies for treating COVID-19-associated bacterial co-infections. Further investigation is needed, which may lead to effective treatments for managing secondary bacterial infections in viral disease contexts.

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来源期刊
Antibiotics-Basel
Antibiotics-Basel Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics
CiteScore
7.30
自引率
14.60%
发文量
1547
审稿时长
11 weeks
期刊介绍: Antibiotics (ISSN 2079-6382) is an open access, peer reviewed journal on all aspects of antibiotics. Antibiotics is a multi-disciplinary journal encompassing the general fields of biochemistry, chemistry, genetics, microbiology and pharmacology. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on the length of papers.
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