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 (CO^δ---NH^δ+). 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.

背景：生物活性分子与 HIV-1 病毒之间相互作用的研究一直是药物化学和药理学领域近期研究的重点。

目的：研究阐明和鉴定抗病毒药效团位点的结构参数和理化性质。

方法：开发了一种基于混合计算 Petra/Osiris/Molinspiration/DFT (POM/DFT) 的模型，用于鉴定控制 22 3-hydroxy-indolin-2-one 衍生物生物活性的理化参数。酒石酸和芳香胺含有组合的抗病毒/抗肿瘤/抗菌药效团位点。用 HIV-1 整合酶 (pdb ID: 5KGX) 进行了分子对接研究，以提供有关酶结合位点相互作用的信息。

结果：化合物 3a-5j 的物理化学性质和几何参数的 POM 分析表明，它们带有两个组合的 (O,O)-口袋，导致一个能够协调两种过渡金属的特殊平台。与标准药物相比，3a-5j 系列增加的活性包含 (Osp ² ,O sp ³ ,O sp ² )-药效团位点。生物活性从 4b (R ¹ , R ² = H, H) 到 3d (R ¹ , R ² = 4-Br, 2-OCH ₃ ) 的增加可归因于对溴的 π-电荷转移的存在-苯基与其酰胺基（CO ^δ- --NH ^δ+）。类似于基于吲哚的参考配体（pdb：7SK），化合物 3d 在酶的催化核心域中的 HIV-1 整合酶的残基 Glu170、Thr174 和 His171 之间形成氢键相互作用。

结论：研究证实了氧原子的重要性，特别是来自苯环的甲氧基和亲电酰胺氮原子对于形成相互作用的重要性。