Molecular topology and QSAR multi-target analysis to boost the in silico research for fungicides in agricultural chemistry
- 56 Downloads
The aim of the present study is to show how molecular topology can be a powerful in silico tool for the prediction of the fungicidal activity of several diphenylamine derivatives against three fungal species (cucumber downy mildew, rice blast and cucumber gray mold). A multi-target QSAR model was developed, and two strategies were followed. First is the construction of a virtual library of molecules using DesMol2 program and a subsequent selection of potential active ones. Second is the selection of molecules from the literature on the basis of molecular scaffolds. More than 700 diphenylamine derivatives designed and other 60 fluazinam’s derivatives with structural similarity higher than 80% were studied. Almost twenty percent of the molecules analyzed show potential activity against the three fungal species.
KeywordsQSAR Molecular topology Drug design Agro-chemistry Fungicides
Authors acknowledge the MINECO (Spanish Ministry of Economy, Industry and Competitivity) Project: “Desarrollo de nuevas herramientas para el control de oidios” (AGL2016-76216-C2-2-R). I.GP acknowledges the MECD (Spanish Ministry of Education, Culture and Sport) Program: “University teacher formation,” to carry out this study.
- 1.Kumar A, Tiwari A, Sharma A (2018) Changing paradigm from one target one ligand towards multi target directed ligand design for key drug targets of Alzheimer disease: an important role of in silico methods in multi target directed ligands design. Curr Neuropharmacol. https://doi.org/10.2174/1570159x16666180315141643 CrossRefPubMedGoogle Scholar
- 2.Abeijon P, Garcia-Mera X, Caamano O, Yanez M, Lopez-Castro E, Romero-Duran FJ, Gonzalez-Diaz H (2017) Multi-target mining of alzheimer disease proteome with Hansch’s QSBR-perturbation theory and experimental-theoretic study of new thiophene isosters of rasagiline. Curr Drug Targets 18(5):511–521. https://doi.org/10.2174/1389450116666151102095243 CrossRefPubMedGoogle Scholar
- 9.Zanni R, Galvez-Llompart M, Morell C, Rodríguez-Henche N, Díaz-Laviada I, Recio-Iglesias MC, Garcia-Domenech R, Galvez J (2015) Novel cancer chemotherapy hits by molecular topology: dual Akt and Beta-catenin inhibitors. PLoS ONE 10(4):e0124244. https://doi.org/10.1371/journal.pone.0124244 CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Gladieux P, Ravel S, Rieux A, Cros-Arteil S, Adreit H, Milazzo J, Thierry M, Fournier E, Terauchi R, Tharreau D (2018) Coexistence of multiple endemic and pandemic lineages of the rice blast pathogen. MBio 9(2):e01806–e01817. https://doi.org/10.1128/mBio.01806-17 CrossRefPubMedPubMedCentralGoogle Scholar
- 20.ChemDraw Ultra package (version 10.0) (2009) CambridgeSoftGoogle Scholar
- 21.Kier LB, Hall LH (1986) Molecular connectivity in structure-activity analysis, 1st edn. Research Studies Press, LetchworthGoogle Scholar
- 24.Garcia-Pereira I (2018) Desmol2 software. Department of Physical Chemistry. Faculty of Pharmacy. University of Valencia. http://desmol2.uv.es
- 25.Klecka WR (1980) Discriminant analysis. Sage University paper series on quantitative applications in the social sciences, 1st edn. Sage Publications, Beverly HillsGoogle Scholar
- 26.StatSoft I. Statistica (data analysis software system) (2009) Version 9. Tulsa, USAGoogle Scholar
- 28.Roderick LJA, Rubin DB (2014) Statistical analysis with missing data, vol 333. Wiley, HobokenGoogle Scholar
- 30.ChemIDplus A TOXNET DATABASE (2018) https://chem.nlm.nih.gov/chemidplus/