Design, Synthesis and 3D‐QSAR of New Quinazolin‐4(3H)‐one Derivatives Containing a Hydrazide Moiety as Potential Fungicides

Abstract

A series of quinazolin‐4(3H)‐one derivatives containing a hydrazide moiety were designed, synthesized and characterized in detail via FT‐IR, 1H NMR, 13C NMR and HRMS spectra. The antifungal activities against Rhizoctonia solani (Rs) and Fusarium graminearum (Fg) were evaluated in vitro. The bioassay results indicated that most of the title compounds exhibited significant antifungal activities against Rs and Fg. Strikingly, the EC50 values of some title compounds against Rs are obviously superior to that of the positive control carbendazim. Based on the antifungal bioassay results against Rs, the comparative molecular filed analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) models were generated to investigate the structure‐activity relationship of title compounds against Rs. The analytical results indicated that these two models exhibited good predictive accuracies and could provide significant structural insights for the design of bioactive quinazolin‐4(3H)‐one derivatives containing a hydrazide moiety.

Design, Synthesis, and Antifungal Evaluation of Neocryptolepine Derivatives against Phytopathogenic Fungi

“…In this context, natural products have emerged as highly promising sources of lead candidates for use in small-molecule drug discovery . It has been shown that essential features of natural products are chemical diversity and diversity in biological functions, making natural product libraries favorable and attractive in drug discovery . Nonetheless, the paucity of these biologically active products in native plants and the challenges of extracting the target compounds from other metabolites with similar chemical properties have hindered research interests in this area .…”

Synthesis, Bioactivity Evaluation,3D‐QSAR, and Molecular Docking of Novel Pyrazole‐4‐carbohydrazides as Potential Fungicides Targeting Succinate Dehydrogenase

“…indicated the reliable predictive accuracy of 3D‐QSAR models. [ 33‐36 ] Contour maps for the CoMFA and CoMSIA models were displayed in Figure 4. Actual and predicted pEC 50 values for the training set and test set were reported in Table 2, and the correlation plots of CoMFA and CoMSIA models were shown in Figure 5.…”

“…The antifungal activities of the synthesized compounds were tested in vitro against R. solani , F. graminearum , B. cinerea and C. cinerea by a mycelium growth rate method, with carbendazim as the positive control. [ 33‐35 ] The tested fungal strains were provided by the Laboratory of Plant Disease Control, Nanjing Agricultural University. The target compounds with inhibition rates exceeding 50% at the concentration of 10 μg/mL were further tested for their antifungal inhibition rates at five different concentrations to calculate the corresponding EC 50 values.…”

“…Partial least square (PLS) regression analysis was used to derive CoMFA and CoMSIA models. [ 33‐35 ]…”

“…3D‐QSAR research reveals the mode of binding of drug molecules and biological macromolecules by calculating the physical and chemical properties and structural parameters of compounds, and predicts or explains the pharmacological activity of small organic molecules. [ 33‐36 ] Therefore, based on the results of 3D‐QSAR research, analyzing the characteristics of receptors or pharmacological targets to rationally design new molecular skeletons is a very important drug molecular design strategy. According to our previous investigation on the pyrazole derivatives and corresponding 3D‐QSAR model, we found that the positive charge groups and hydrogen bond acceptors are favored at hydrazone position to improve the antifungal activity (Figure 1).…”