QSAR, ADMET, and Molecular Docking of Pyrazole Carboxamide Derivatives as Potential Antifungals Against the Fungus Rhizoctonia solani
Ranggaweny Al-Ghani (a), Adani Ghina Puspita Sari (a), Tria Nurwina Novianti (a), Hafiz Aji Aziz, M.Sc (a*)

a) Department of Chemistry Education, Faculty of Mathematics and Natural Sciences Education, Universitas Pendidikan Indonesia
Jl. Dr. Setiabudhi No. 229, Bandung 40154, Indonesia
*ha.aziz[at]upi.edu

Abstract

Sheath blight is generally caused by the fungus Rhizoctonia solani. The emergence of this fungus has caused losses to farmers because it reduces the production of grain crops (cerelia) such as rice. Thus, the use of antifungal compounds containing succinate dehydrogenase inhibitors is an effort to control sheath blight of the fungus R. solani. In this research, we have studied a new pyrazole carboxamide derivative designed as a succinate dehydrogenase inhibitor. Predicted antifungal activity values were determined using the Quantitative Structure-Activity Relationship (QSAR) equation and visualization of the interaction of pyrazole carboxamide derivatives with succinate dehydrogenase inhibitors was determined using molecular docking. As many as 29 pyrazole carboxamide derivatives and activities (EC50) were used in this study for QSAR modelling and molecular docking. The structure has been optimized using the DFT/B3LYP/LanL2DZ method as an electronic descriptor calculation and QSAR modelling using the Multiple Linear Regression (MLR) method. The MLR test shows a valid QSAR equation model with good modelling accuracy and produces an equation :
log⁡ EC50 = 2,3936 (±0,9447) [C13] + 9,1367 (±3,0682) [C10] + 2,2473 (±0,6055)[HOMO] - 48,1289 (±14,1289) [C4] + 1,3937 (±0,9465) [C14] + 28,3750 (±6,6731)
with Rtr^2 = 0,8911- Q^2 = 0,793- F = 28,079- Rval^2 = 0,9908- RMSE=0,3450
ADMET analysis with admetlab indicated that the new pyrazole carboxamide derivative complies with Lipinski^s rules, is moderately carcinogenic, and includes inhibiting the activity of hERG blockers. The new pyrazole carboxamide derivative compounds that have the potential as succinate dehydrogenase inhibitors were determined based on the interaction of the docking results, namely compound A1 with a docking score of -4.9 kcal/mol, compound A5 with a docking score of -5.1 kcal/mol, and compound A7 with a docking score of - 5.3 kcal/mol.

Keywords: QSAR, molecular docking, MLR, ADMET, antifungal

Topic: Chemistry