Nano route with DFT, docking studies, ADMET, and SAR of a pyran-functionalized pyrimidine scaffold as a potent Rhizoctonia solani

Abstract Numerous plant infections known as phytopathogenic fungi are responsible for a broad range of agricultural illnesses. Recent research focuses on developing, synthesizing, and evaluating pyran-linked pyrimidine hybrids as potential antifungals. In this study, the target hybrids of the pyran-functionalized pyrimidine scaffold were optimized synthesized using nanoscience-based techniques. A multi-step process involving nucleophilic substitution reaction, cyclization, acetylation, hydrolysis, condensation, and Dimroth rearrangement afforded pyran-pyrimidine hybrids 1–7. In this study, the antifungal potency of optimized synthesized compounds (3, 5, and 6) against various therapeutic targets of the phytopathogenic fungus Rhizoctonia solani was assessed using a thorough computational approach. Investigated hybrids, especially 3, 5, and 6 at 20 ppm and 50 ppm, exhibited strong resistance to the fungus Rhizoctonia solani , representing a potential antifungal control against soil-borne plant pathogens. Molecular docking analyses revealed these compounds exhibit potent, multi-target binding affinities, frequently outperforming the reference drug fluconazole, particularly against sterol-14-alpha-demethylase, chitin synthase, cellulose synthase, and cytochrome bc 1 . Simulations involving molecular dynamics and MM-GBSA (Molecular Mechanics/Generalized Born Surface Area)/PBSA (Poisson-Boltzmann Surface Area) free energy computations over trajectories for compound 3 confirmed the formation of highly stable and dynamically viable complexes. Pharmacokinetically and according to ADMET assessments, tested hybrids comply with accepted drug-likeness rules (Lipinski, Pfizer, and Golden Triangle) and present minimal risk of cytochrome P450 inhibition. According to findings of computational analyses that confirmed fungal potency evaluation, optimized synthesized compounds are promising bioactive candidates for developing effective fungicides. This study is the first to compare the protective effects of pyran-functionalized pyrimidine against Rhizoctonia solani supported by computational analyses.