In silico studies of novel pyrazole-furan and pyrazole-pyrrole carboxamide as fungicides against Sclerotinia sclerotiorum

Abstract

Background: 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. Results: 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. Conclusion: 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).