Alimi Livani, Z., Safakish, M., Hajimahdi, Z., Soleymani, S., Zabihollahi, R., Aghasadeghi, M., Alipour, E., Zarghi, A. (2018). Design, Synthesis, Molecular Modeling, In Silico ADME Studies and Anti-HIV-1 Assay of New Diazocoumarin Derivatives. Iranian Journal of Pharmaceutical Research, 17(Special Issue 2), 65-77. doi: 10.22037/ijpr.2018.2376
Zeynab Alimi Livani; Mahdieh Safakish; Zahra Hajimahdi; Sepehr Soleymani; Rezvan Zabihollahi; Mohammad Reza Aghasadeghi; Eskandar Alipour; Afshin Zarghi. "Design, Synthesis, Molecular Modeling, In Silico ADME Studies and Anti-HIV-1 Assay of New Diazocoumarin Derivatives". Iranian Journal of Pharmaceutical Research, 17, Special Issue 2, 2018, 65-77. doi: 10.22037/ijpr.2018.2376
Alimi Livani, Z., Safakish, M., Hajimahdi, Z., Soleymani, S., Zabihollahi, R., Aghasadeghi, M., Alipour, E., Zarghi, A. (2018). 'Design, Synthesis, Molecular Modeling, In Silico ADME Studies and Anti-HIV-1 Assay of New Diazocoumarin Derivatives', Iranian Journal of Pharmaceutical Research, 17(Special Issue 2), pp. 65-77. doi: 10.22037/ijpr.2018.2376
Alimi Livani, Z., Safakish, M., Hajimahdi, Z., Soleymani, S., Zabihollahi, R., Aghasadeghi, M., Alipour, E., Zarghi, A. Design, Synthesis, Molecular Modeling, In Silico ADME Studies and Anti-HIV-1 Assay of New Diazocoumarin Derivatives. Iranian Journal of Pharmaceutical Research, 2018; 17(Special Issue 2): 65-77. doi: 10.22037/ijpr.2018.2376
Design, Synthesis, Molecular Modeling, In Silico ADME Studies and Anti-HIV-1 Assay of New Diazocoumarin Derivatives
1Department of Organic Chemistry, Tehran North Branch, Islamic Azad University, Tehran, Iran.
2Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3Hepatitis and AIDS department, Pasteur institute of Iran, Tehran, Iran.
4Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
5Department of Organic Chemistry, Tehran North Branch, Islamic Azad University, Tehran, Iran
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.
Top