Design and statistical optimisation of emulsomal nanoparticles for improved anti-SARS-CoV-2 activity of N-(5-nitrothiazol-2-yl)-carboxamido candidates: in vitro and in silico studies

被引：12

作者：

Al-Karmalawy, Ahmed A. A. ^{[1
]}

El-Gamil, Dalia S. S. ^{[1
]}

El-Shesheny, Rabeh ^{[2
]}

Sharaky, Marwa ^{[3
]}

Alnajjar, Radwan ^{[4
,5
,6
]}

Kutkat, Omnia ^{[2
]}

Moatasim, Yassmin ^{[2
]}

Elagawany, Mohamed ^{[7
]}

Al-Rashood, Sara T. T. ^{[8
]}

Binjubair, Faizah A. A. ^{[8
]}

Eldehna, Wagdy M. M. ^{[9
,10
]}

Noreddin, Ayman M. M. ^{[11
,12
]}

Zakaria, Mohamed Y. Y. ^{[13
]}

机构：

[1] Ahram Canadian Univ, Fac Pharm, Pharmaceut Chem Dept, Giza, Egypt

[2] Natl Res Ctr, Environm Res Inst, Ctr Sci Excellence Influenza Viruses, Water Pollut Res Dept, Giza, Egypt

[3] Cairo Univ, Natl Canc Inst NCI, CancerBiol Dept, Pharmacol Unit, Cairo, Egypt

[4] Univ Benghazi, Fac Sci, Dept Chem, Benghazi, Libya

[5] Libyan Int Med Univ, Fac Pharm, Benghazi, Libya

[6] Univ Cape Town, Dept Chem, Rondebosch, South Africa

[7] Damanhour Univ, Fac Pharm, Dept Pharmaceut Chem, Damanhour, Egypt

[8] King Saud Univ, Coll Pharm, Dept Pharmaceut Chem, Riyadh, Saudi Arabia

[9] Kafrelsheikh Univ, Fac Pharm, Dept Pharmaceut Chem, Kafrelsheikh, Egypt

[10] Badr Univ Cairo, Sch Biotechnol, Badr City, Egypt

[11] Univ Calif Irvine, Sch Med, Dept Internal Med, Irvine, CA USA

[12] Ahram Canadian Univ, Fac Pharm, Dept Clin Pharm, Giza, Egypt

[13] Port Said Univ, Fac Pharm, Dept Pharmaceut, Ind Pharm, Port Said, Egypt

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2023年 / 38卷 / 01期

关键词：

N-(5-nitrothiazol-2-yl)-carboxamide; emulsomes; anti-SARS-CoV-2; mechanistic study; SAR; MOLECULAR-DYNAMICS; INHIBITORS; SARS-COV-2; PERMEATION; DISCOVERY; DELIVERY;

D O I：

10.1080/14756366.2023.2202357

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In this article, emulsomes (EMLs) were fabricated to encapsulate the N-(5-nitrothiazol-2-yl)-carboxamido derivatives (3a-3g) in an attempt to improve their biological availability and antiviral activity. Next, both cytotoxicity and anti-SARS-CoV-2 activities of the examined compounds loaded EMLs (F3a-g) were assessed in Vero E6 cells via MTT assay to calculate the CC50 and inhibitory concentration 50 (IC50) values. The most potent 3e-loaded EMLs (F3e) elicited a selectivity index of 18 with an IC50 value of 0.73 mu g/mL. Moreover, F3e was selected for further elucidation of a possible mode of action where the results showed that it exhibited a combination of virucidal (>90%), viral adsorption (>80%), and viral replication (>60%) inhibition. Besides, molecular docking and MD simulations towards the SARS-CoV-2 Mpro were performed. Finally, a structure-activity relationship (SAR) study focussed on studying the influence of altering the size, type, and flexibility of the alpha-substituent to the carboxamide in addition to compound contraction on SARS-CoV-2 activity.

引用

页数：19

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