Design, Synthesis, Molecular Modeling, In Silico ADME Studies and Anti-HIV-1 Assay of New Diazocoumarin Derivatives

Alimi Livani, Zeynab; Safakish, Mahdieh; Hajimahdi, Zahra; Soleymani, Sepehr; Zabihollahi, Rezvan; Aghasadeghi, Mohammad Reza; Alipour, Eskandar; Zarghi, Afshin

doi:10.22037/ijpr.2018.2376

Design, Synthesis, Molecular Modeling, In Silico ADME Studies and Anti-HIV-1 Assay of New Diazocoumarin Derivatives

Document Type: Research article

Authors

¹ Department of Organic Chemistry, Tehran North Branch, Islamic Azad University, Tehran, Iran.

² Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

³ Hepatitis and AIDS department, Pasteur institute of Iran, Tehran, Iran.

⁴ Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.

⁵ Department of Organic Chemistry, Tehran North Branch, Islamic Azad University, Tehran, Iran

10.22037/ijpr.2018.2376

Abstract

Some new diazo incorporated coumarin compounds were designed and synthesized to evaluate their anti-HIV activity. Overall, compounds were active against HIV at 100 μM. Additionally, no cytotoxic effect was observed at this concentration. The compound with 4-chlorobenzyl group indicated the best anti-HIV activity (52%). Docking studies using the later crystallographic data available for PFV integrase showed similar binding modes to HIV-1 integrase inhibitors. On the basis of these data, nitrogen atoms of 1,3,4-oxadiazole ring have been involved in the Mg2+ chelation and 4-chlorobenzyl group occupies the same position as 4-flourobenzyl group of raltegravir in the active site. In addition, in silico ADME assay demonstrated favorable physicochemical properties for the new designed compounds. Thus, synthesized structures could be introduced as a novel template for designing safe anti-HIV compounds with integrase inhibitory potential.

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