Pyrazole-furan and pyrazole-pyrrole moiety are among the molecular structures that were found to have an extensive range of applications in the field of medicine and agrochemical due to their wide spectrum of biological activities. These include antimicrobial activity, anti-glaucoma activity, ocular hypertension activity, and antifungal activity. An in silico study was carried out on 37 compounds of pyrazole-furan and pyrazole-pyrrole carboxamide derivatives against Sclerotinia sclerotiorum. Using Spartan 14 software, optimization of the compounds was performed at the DFT/B3LYP/6-31G* quantum mechanical method. PaDEL descriptor software was used to calculate the molecular descriptors, and a Generic Function Approximation (GFA) was employed to generate the model. Out of four models generated, model 1 was found to be the optimal and has the following statistical parameters; R2 = 0.83485, R2adj = 0.793563, cross-validated R2 = 0.74037, and external R2 = 0.58479. Molecular docking study was carried out between the antifungal compounds, and the binding site of S. sclerotiorum (PDB CODE 2X2S) in which compound 7 was identified to have the highest binding energy of − 7.5kcal/mol. This compound “7” has a strong affinity with the macromolecular target point of the S. sclerotiorum (2x2s), producing H-bond and as well as the hydrophobic interaction at target point of the amino acid residue. Considering compound 7 as our scaffold, four (4) more potent compounds (7a, 7b, 7c, and 7d) were designed using optimization method of structure-based designed which have the following docking score, − 7.7, − 7.8, − 7.7, and − 7.7kcal/mol. Statistical analyses including variance inflation factor (VIF), mean effect (ME), and applicability domain were conducted on the model. Considering an interpretation of the descriptors given in the discussion, the QSAR model provided an idea of ligand-based design while the molecular docking gave an insight on structure-based design of the new compounds with better activity against S. sclerotiorum in which four (4) compounds 7a, 7b, 7c, and 7d were designed and discovered to be of high quality and have greater binding affinity compared to the one obtained from the literature (compound 7).

中文翻译：

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新型吡唑-呋喃和吡唑-吡咯甲酰胺作为杀菌剂对抗核盘菌的计算机研究

吡唑-呋喃和吡唑-吡咯部分由于其广泛的生物活性而被发现在医药和农用化学品领域具有广泛的应用范围。这些包括抗微生物活性、抗青光眼活性、高眼压活性和抗真菌活性。对 37 种吡唑-呋喃和吡唑-吡咯甲酰胺衍生物化合物对抗核盘菌进行了计算机模拟研究。使用 Spartan 14 软件，以 DFT/B3LYP/6-31G* 量子力学方法对化合物进行优化。PaDEL描述符软件用于计算分子描述符，并采用通用函数近似（GFA）来生成模型。在生成的四个模型中，发现模型 1 是最优的，并且具有以下统计参数；R2 = 0.83485，R2adj = 0.793563，交叉验证的 R2 = 0.74037，外部 R2 = 0.58479。在抗真菌化合物与核盘菌结合位点（PDB CODE 2X2S）之间进行了分子对接研究，其中化合物7被鉴定为具有-7.5kcal/mol的最高结合能。这种化合物“7”与核盘菌的大分子靶点（2x2s）有很强的亲和力，产生氢键，以及氨基酸残基靶点的疏水相互作用。考虑化合物 7 作为我们的支架，使用基于结构设计的优化方法设计了四 (4) 个更有效的化合物（7a、7b、7c 和 7d），它们具有以下对接分数，- 7.7，- 7.8，- 7.7， - 7.7kcal/mol。对该模型进行了方差膨胀因子（VIF）、平均效应（ME）和适用性域等统计分析。考虑到对讨论中给出的描述符的解释，QSAR 模型提供了基于配体的设计思想，而分子对接提供了基于结构设计的新化合物的见解，这些化合物对核盘菌具有更好的活性，其中四 (4 ) 设计并发现化合物 7a、7b、7c 和 7d 具有高质量，并且与从文献中获得的化合物（化合物 7）相比具有更高的结合亲和力。