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

Authors:
Zahra Hajimahdi
Zahra Hajimahdi
Shahid Beheshti University of Medical Sciences
Iran
Sepehr Soleymani
Sepehr Soleymani
School of Medicine
New York | United States
Rezvan Zabihollahi
Rezvan Zabihollahi
Pasteur Institute of Iran
Iran
Mohammad Reza Aghasadeghi
Mohammad Reza Aghasadeghi
Pasteur Institute of Iran
Tehran | Iran
Afshin Zarghi
Afshin Zarghi
School of Pharmacy
Iran

Iran J Pharm Res 2018 ;17(Suppl2):65-77

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

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 Mg chelation and 4-chlorobenzyl group occupies the same position as 4-flourobenzyl group of raltegravir in the active site. In addition, 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447871PMC
January 2018
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