Novel 5-Sulfonyl-1,3,4-thiadiazole-Substituted Flavonoids as Potential Bactericides and Fungicides: Design, Synthesis, Three-Dimensional Quantitative Structure–Activity Relationship Studies

Abstract

Flavonoids, ubiquitous natural products, provide sources for drug discovery owing to their structural diversity, broadspectrum pharmacological activity, and excellent environmental compatibility. To develop antibacterial and antifungal agents with novel mechanisms of action and innovative structures, a series of novel 5-sulfonyl-1,3,4-thiadiazole-substituted flavonoids were designed and synthesized, and their biological activities against seven agriculturally common phytopathogenic microorganisms were evaluated. The results of the antimicrobial bioassay showed that most of the target compounds displayed excellent inhibitory effects against Xanthomonas oryzae, Rhizoctonia solani, and Colletotrichum orbiculare. Compounds 1, 3, 7, 9, 13, and 14 exhibited remarkable antibacterial activity against X. oryzae pv. oryzae with EC 50 values below 10 μg/mL, which were superior to bismerthiazol (70.89 μg/ mL). Compound 2 (EC 50 = 0.41 μg/mL) displayed the most effective inhibitory potency against R. solani in vivo, comparable protective effects with the positive control carbendizam. Preliminary mechanistic studies indicated that compound 2 induced disordered entanglement of hyphae, shrinkage of hyphal surfaces, extravasation of cellular contents, and vacuole swelling and rupture, which disrupted normal hyphal growth. Subsequently, compounds 35−53 with good antifungal activity were designed and synthesized based on reliable three-dimensional quantitative structure−activity relationship (3D-QSAR) models. Compound 49 showed high efficacy and superior antifungal activity against R. solani, with an EC 50 value of 0.28 μg/mL and a half-maximal effective concentration of 0.46 μg/mL.

3D-QSAR-Directed Synthesis of Halogenated Coumarin-3-Hydrazide Derivatives: Unveiling Their Potential as SDHI Antifungal Agents

“…This process involved 1000 iterations and aimed for a convergence gradient of 0.005 kcal/mol Å. Subsequently, the field properties for both the CoMFA and CoMSIA models were determined through PLS analysis. , …”

Recent Advances and Outlook of Benzopyran Derivatives in the Discovery of Agricultural Chemicals

“…The two main isomers of benzopyran are benzo-α-pyran and benzo-γ-pyran, while benzodihydropyran, chroman-2-one, chroman-4-one, and 4 H -chromen-4-one contain variations in the scaffold structures of benzopyran (Figure ). In addition, some representative natural products containing a benzopyran structure have played an important role in the discovery of agricultural active compounds, − such as osthole and coumarin.…”