Title:Petra/Osiris/Molinspiration and Molecular Docking Analyses of 3-Hydroxy-Indolin-2-one Derivatives as Potential Antiviral Agents
VOLUME: 17 ISSUE: 1
Author(s):Taibi Ben Hadda*, Vesna Rastija*, Faisal AlMalki, Abderrahim Titi, Rachid Touzani, Yahia N. Mabkhot, Shah Khalid, Abdelkader Zarrouk and Bina S. Siddiqui
Affiliation:Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm AlQura University, Makkah, Department of Agroecology and Environmental Protection, Faculty of Agrobiotechnical Sciences Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm AlQura University, Makkah, LCAE-LCM Laboratories, Faculty of Sciences, University Mohammed Premier, Oujda, LCAE-LCM Laboratories, Faculty of Sciences, University Mohammed Premier, Oujda, Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha, Department of Botany, Islamia College, Peshawar, Laboratory of Materials, Nanotechnology and Environment, Faculty of Sciences, Mohammed V University, Agdal-Rabat, HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi
Keywords:3-Hydroxy-indolin-2-ones, POM analyses, HIV antiviral activity, pharmacophore, molecular docking, HIV-1 integrase.
Abstract:
Background: Studies on the interaction between bioactive molecules and HIV-1 virus
have been the focus of recent research in the scope of medicinal chemistry and pharmacology.
Objective: Investigating the structural parameters and physico-chemical properties of elucidating
and identifying the antiviral pharmacophore sites.
Methods: A mixed computational Petra/Osiris/Molinspiration/DFT (POM/DFT) based model has
been developed for the identification of physico-chemical parameters governing the bioactivity of
22 3-hydroxy-indolin-2-one derivatives of diacetyl-L-tartaric acid and aromatic amines containing
combined antiviral/antitumor/antibacterial pharmacophore sites. Molecular docking study was carried
out with HIV-1 integrase (pdb ID: 5KGX) in order to provide information about interactions
in the binding site of the enzyme.
Results: The POM analyses of physico-chemical properties and geometrical parameters of compounds
3a-5j, show that they are bearing a two combined (O,O)-pockets leading to a special platform
which is able to coordinate two transition metals. The increased activity of series 3a-5j, as
compared to standard drugs, contains (Osp2,O sp3,O sp2)-pharmacophore site. The increase in bioactivity
from 4b (R1, R2 = H, H) to 3d (R1, R2 = 4-Br, 2-OCH3) could be attributed to the existence
of π-charge transfer from para-bromo-phenyl to its amid group (COδ---NHδ+). Similar to the
indole-based reference ligand (pdb: 7SK), compound 3d forms hydrogen bonding interactions between
the residues Glu170, Thr174 and His171 of HIV-1 integrase in the catalytic core domain of
the enzyme.
Conclusion: Study confirmed the importance of oxygen atoms, especially from the methoxy group
of the phenyl ring, and electrophilic amide nitrogen atom for the formation of interactions.
