数字中医药（英文）2021，Vol.4Issue(2)：102-119,18.DOI:10.1016/j.dcmed.2021.06.004
新型嘧啶-苯并咪唑杂合物的抗细菌和抗真菌特性及其对新冠病毒主要蛋白酶和刺突糖蛋白的潜在抑制作用
Novel pyrimidine-benzimidazole hybrids with antibacterial and antifungal properties and potential inhibition of SARS-CoV-2 main protease and spike glycoprotein
Sharuk Khan 1Mayura Kale 2Falak Siddiqui 1Nitin Nema3
作者信息
- 1. Department of Pharmaceutical Chemistry, MUP's College of Pharmacy (B Pharm), Washim, Maharashtra 444504, India
- 2. Department of Pharmaceutical Chemistry, Government College of Pharmacy, Aurangabad, Maharashtra 431003, India
- 3. Department of Pharmacology, Shri Vile Parle Kelavani Mandal’s (SVKM’s) Institute of Pharmacy, Dhule, Maharashtra 424001, India
- 折叠
摘要
Abstract
Objective The study aimed to synthesize and characterize pyrimidine-linked benzimidazole hybrids, define their antimicrobial and antifungal activities in vitro , and determine their ability to inhibit the main protease and spike glycoprotein of SARS-CoV-2. Methods The ability of the synthesized compounds to inhibit the main protease and spike glycoprotein inhibitory of SARS-CoV-2 was investigated by assessing their mode of binding to the allosteric site of the enzyme using molecular docking. The structures of pyrimidine-linked benzimidazole derivatives synthesized with microwave assistance were confirmed by spectral analysis. Antibacterial and antifungal activities were determined by broth dilution. Results Gram-negative bateria (Escherichia coli and Pseudomonas aeruginosa ) were more sensitive than gram-positive bateria ( Staphylococcus aureus and Streptococcus pyogenes) to the derivatives. Candida albicans was sensitive to the derivatives at a minimal inhibitory concentration (MIC) of 250 μg/mL. The novel derivatives had better binding affinity (kcal/mol) than nelfinavir, lopinavir, ivermectin, remdesivir, and favipiravir, which are under investigation as treatment for SARS-CoV-2 infection. Compounds 2c, 2e, and 2g formed four hydrogen bonds with the active cavity of the main protease. Many derivatives had good binding affinity for the RBD of the of SARS-CoV-2 spike glycoprotein with the formation of up to four hydrogen bonds. Conclusion We synthesized novel pyrimidine-linked benzi-midazole derivatives that were potent antimicrobial agents with ability to inhibit the SARS-CoV-2 spike glycoprotein. Understanding the pharmacophore features of the main protease and spike glycoprotein offers much scope for the development of more potent agents. We plan to optimize the properties of the derivatives using models in vivo and in vitro so that they will serve as more effective therapeutic options against bacterial and SARS-CoV-2 infections.关键词
新型冠状病毒抑制剂/新型冠状病毒肺炎/分子对接/嘧啶-苯并咪唑/细菌/抗真菌Key words
SARS-CoV-2 inhibitor/COVID-19/Molecular docking/Pyrimidine-benzimidazole/Bacteria/Antifungal引用本文复制引用
Sharuk Khan,Mayura Kale,Falak Siddiqui,Nitin Nema..新型嘧啶-苯并咪唑杂合物的抗细菌和抗真菌特性及其对新冠病毒主要蛋白酶和刺突糖蛋白的潜在抑制作用[J].数字中医药（英文）,2021,4(2):102-119,18.
