Putz Mihai V, Duda-Seiman Corina, Duda-Seiman Daniel, Putz Ana-Maria, Alexandrescu Iulia, Mernea Maria, Avram Speranta
Laboratory of Computational and Structural Physical-Chemistry for Nanosciences and QSAR, Department of Biology-Chemistry, West University of Timişoara, Pestalozzi Str. 16, RO-300115 Timisoara, Romania.
Laboratory of Renewable Energies-Photovoltaics, R & D National Institute for Electrochemistry and Condensed Matter, Dr. A. Paunescu Podeanu Str. No. 144, RO-300569 Timisoara, Romania.
Int J Mol Sci. 2016 Jul 8;17(7):1087. doi: 10.3390/ijms17071087.
Within medicinal chemistry nowadays, the so-called pharmaco-dynamics seeks for qualitative (for understanding) and quantitative (for predicting) mechanisms/models by which given chemical structure or series of congeners actively act on biological sites either by focused interaction/therapy or by diffuse/hazardous influence. To this aim, the present review exposes three of the fertile directions in approaching the biological activity by chemical structural causes: the special computing trace of the algebraic structure-activity relationship (SPECTRAL-SAR) offering the full analytical counterpart for multi-variate computational regression, the minimal topological difference (MTD) as the revived precursor for comparative molecular field analyses (CoMFA) and comparative molecular similarity indices analysis (CoMSIA); all of these methods and algorithms were presented, discussed and exemplified on relevant chemical medicinal systems as proton pump inhibitors belonging to the 4-indolyl,2-guanidinothiazole class of derivatives blocking the acid secretion from parietal cells in the stomach, the 1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio)thymine congeners' (HEPT ligands) antiviral activity against Human Immunodeficiency Virus of first type (HIV-1) and new pharmacophores in treating severe genetic disorders (like depression and psychosis), respectively, all involving 3D pharmacophore interactions.
在当今药物化学领域，所谓的药效学旨在寻找定性（用于理解）和定量（用于预测）机制/模型，通过这些机制/模型，特定的化学结构或一系列同系物能够通过聚焦相互作用/治疗或通过扩散/有害影响，在生物位点上发挥积极作用。为此，本综述揭示了从化学结构原因探究生物活性的三个富有成果的方向：代数结构-活性关系的特殊计算轨迹（SPECTRAL-SAR），它为多变量计算回归提供了完整的分析对应物；最小拓扑差异（MTD），作为比较分子场分析（CoMFA）和比较分子相似性指数分析（CoMSIA）的复兴前身；所有这些方法和算法都在相关的化学药物体系中进行了介绍、讨论和举例说明，这些体系包括属于4-吲哚基、2-胍基噻唑类衍生物的质子泵抑制剂，它们可阻断胃壁细胞的酸分泌；1-[(2-羟基乙氧基)-甲基]-6-(苯硫基)胸腺嘧啶同系物（HEPT配体）对1型人类免疫缺陷病毒（HIV-1）的抗病毒活性，以及分别用于治疗严重遗传疾病（如抑郁症和精神病）的新药效团，所有这些都涉及三维药效团相互作用。
