The Custom R Group Enumeration with Various R Group Libraries at Designated Sites on Amphotericin B.

IF 1.5 4区医学 Q4 CHEMISTRY, MEDICINAL

Current computer-aided drug design Pub Date : 2023-01-01 DOI:10.2174/1573409919666230123144712

Ajay Mahor, Devesh M Sawant, Amit K Goyal

引用次数: 0

Abstract

Background: Amphotericin B is a gold-standard drug, particularly for the treatment of systemic fungal infections. However, its low solubility and permeability limit its application. To improve its bioavailability, AmB may be conjugated with various water-soluble auxiliary groups.

Methods: Custom R group Enumeration was used at the designated sites of Amphotericin B. The designated sites taken into consideration are the carboxyl moiety of the aglycone part and the amine moiety of the glycone part of Amphotericin B for Enumeration purposes. The enumerated molecules were subjected to QikProp properties.

Results: We identified fourteen hits with improved predicted aqueous solubility and cell permeability.

Conclusion: Enumeration might be applicable in improving bioavailability, which could lead to the oral formulation of the Amphotericin B drug.

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两性霉素B指定位点上不同R群库的自定义R群枚举。

背景:两性霉素B是治疗全身性真菌感染的金标准药物。但其溶解度和渗透性较低，限制了其应用。为了提高其生物利用度，AmB可与多种水溶性辅助基团偶联。方法:在Amphotericin B的指定位点采用自定义R组计数，指定位点为Amphotericin B苷元部分的羧基部分和苷元部分的胺基部分进行计数。所列举的分子受到QikProp性质的影响。结果:我们确定了14个hit，其预测的水溶性和细胞通透性都有所提高。结论:计数法可提高两性霉素B的生物利用度，为两性霉素B的口服处方提供依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current computer-aided drug design 医学-计算机：跨学科应用

CiteScore

3.70

自引率

5.90%

发文量

审稿时长

>12 weeks

期刊介绍： Aims & Scope Current Computer-Aided Drug Design aims to publish all the latest developments in drug design based on computational techniques. The field of computer-aided drug design has had extensive impact in the area of drug design. Current Computer-Aided Drug Design is an essential journal for all medicinal chemists who wish to be kept informed and up-to-date with all the latest and important developments in computer-aided methodologies and their applications in drug discovery. Each issue contains a series of timely, in-depth reviews, original research articles and letter articles written by leaders in the field, covering a range of computational techniques for drug design, screening, ADME studies, theoretical chemistry; computational chemistry; computer and molecular graphics; molecular modeling; protein engineering; drug design; expert systems; general structure-property relationships; molecular dynamics; chemical database development and usage etc., providing excellent rationales for drug development.