Naslov
Petra/Osiris/Molinspiration and molecular docking analyses of 3-hydroxy-indolin-2-one derivatives as potential antiviral agents

Autori
Hadda, Taibi Ben ; Rastija, Vesna ; AlMalki, Faisal ; Titi, Abderrahim ; Touzani, Rachid ; Mabkhot, Yahia N. ; Khalid, Shah ; Zarrouk, Abdelkader ; Siddiqui, Bina S.

Izvornik
Current computer-aided drug design (1573-4099) 17 (2021), 1; 123-133

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
3-Hydroxy-indolin-2-ones ; POM analyses ; HIV antiviral activity ; Pharmacophore ; Molecular docking ; HIV-1 integrase

Sažetak
Background: Studies on the interaction between bioactive molecules and HIV-1 virus has been the focus of recent research in the scope of medicinal chemistry and pharmacology. Objective: Investigating the structural parameters and physic-chemical properties of elucidating and identifying of the antiviral pharmacophore sites. Method: 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 enzyme. Results: The POM analyses of physic-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 able to coordinate two transition metals. The increased activity of series 3a-5j, as compared to standard drugs, contains an (Osp2, O sp3, O sp2)-pharmacophore site. The increase of bioactivity from 4b (R1, R2 = H, H) to 3d (R1, R2 = 4-Br, 2-OCH3) could be attributed to the existence of pi-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 catalytic core domain of enzyme. Conclusion: Study confirmed the importance of oxygen atoms, especially from the methoxy group of the phenyl ring, and electrophilic amide nitrogen atom for formation of interactions.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA