Petra/Osiris/Molinspiration and Molecular Docking Analyses of 3-Hydroxy-Indolin-2-one Derivatives as Potential Antiviral Agents

Abstract

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.

QSAR, simulation techniques, and ADMET/pharmacokinetics assessment of a set of compounds that target MAO-B as anti-Alzheimer agent

“…More also, Table 4 shows MLR Y-randomization test, the strength, and consistent of the built model were verified by the coefficient of Y-randomization of 0.6433 shown in Table 4. Interestingly, it was observed that all the validation criteria were fully agreed with the acceptable threshold parameters stated in a literature [36].…”

In vitro potential antiviral SARS-CoV-19- activity of natural product thymohydroquinone and dithymoquinone from Nigella sativa

“…The invention of POM Theory leads us to identify each type of pharmacophore sites with real success, on the basis of semi-empirical data of about 7.000 antibacterial, antifungal, antitumor and antiviral commercial and new drugs. All details of therapeutic applications of POM Theory are given in the literature and the identification of different and various types of pharmacophore sites is well established [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] , [77] , [78] , [79] , [80] , [81] , [82] ,…”

Ellagic Acid as a Potential Inhibitor against the Nonstructural Protein NS3 Helicase of Zika Virus: A Molecular Modelling Study

“…These rules filter the compounds and make the drug candidates orally available. To analyze the oral bioavailability of the plant-derived compounds, the drug-likeness property of the compounds was predicted through the Molinspiration server [ 52 ].…”