Design and Synthesis of Novel Diphenyl Ether Carboxamide Derivatives To Control the Phytopathogenic Fungus Sclerotinia sclerotiorum.

Sclerotinia stem rot (SSR) caused by the phytopathogenic fungus Sclerotinia sclerotiorum has led to serious losses in the yields of oilseed rape and other crops every year. Here, we designed and synthesized a series of carboxamide derivatives containing a diphenyl ether skeleton by adopting the scaffold splicing strategy. From the results of the mycelium growth inhibition experiment, inhibition rates of compounds 4j and 4i showed more than 80% to control S. sclerotiorum at a dose of 50 µg/mL, which is close to that of the positive control (flubeneteram, 95%). Then, the results of a structure-activity relationship study showed that the benzyl scaffold was very important for antifungal activity and that introducing a halogen atom on the benzyl ring would improve antifungal activity. Furthermore, the results of an in vitro activity test suggested that these novel compounds can inhibit the activity of succinate dehydrogenase (SDH), and the binding mode of 4j with SDH was basically similar to that of the flutolanil derivative. Morphological observation of mycelium revealed that compound 4j could cause a damage on the mycelial morphology and cell structure of S. sclerotiorum, resulting in inhibition of the growth of mycelia. Furthermore, in vivo antifungal activity assessment of 4j displayed a good control of S. sclerotiorum (>97%) with a result similar to that of the positive control at a concentration of 200 mg/L. Thus, the diphenyl ether carboxamide skeleton is a new starting point for the discovery of new SDH inhibitors and is worthy of further development.

Design, synthesis, antifungal, and antioxidant activities of (E)-6-((2-phenylhydrazono)methyl)quinoxaline derivatives.

Different substituted phenylhydrazone groups were linked to the quinoxaline scaffold to provide 26 compounds (6a-6z). Their structures were confirmed by (1)H and (13)C NMR, MS, elemental analysis, and X-ray single-crystal diffraction. The antifungal activities of these compounds against Rhizoctonia solani were evaluated in vitro. Compound 6p is the most promising one among all the tested compounds with an EC50 of 0.16 µg·mL(-1), more potent than the coassayed positive control fungicide carbendazim (EC50: 1.42 µg·mL(-1)). In addition, these compounds were subjected to antioxidant assay by employing diphenylpicrylhydrazyl (DPPH) and mice microsome lipid peroxidation (LPO) methods. Most of these compounds are potent antioxidants. The strongest compounds are 6e (EC50: 7.60 µg·mL(-1), DPPH) and 6a (EC50: 0.96 µg·mL(-1), LPO), comparative to or more potent than the positive control Trolox [EC50: 5.90 µg·mL(-1) (DPPH) and 18.23 µg·mL(-1) (LPO)]. The structure and activity relationships were also discussed.

The combination of 4-anilinoquinazoline and cinnamic acid: a novel mode of binding to the epidermal growth factor receptor tyrosine kinase.

A novel type of cinnamic acid quinazoline amide derivatives (20-42), which designed the combination between quinazoline as the backbone and various substituted cinnamic acid as the side chain, have been synthesized and their biological activities were evaluated within cytotoxicity assay firstly and then potent EGFR inhibitory activity. Compound 42 demonstrated the most potent inhibitory activity (IC(50)=0.94 µM for EGFR), which could be optimized as a potential EGFR inhibitor in the further study. Docking simulation was performed to position compound 42 into the EGFR active site to determine the probable binding model. Analysis of the binding conformation of 42 in active site displayed compound 42 was stabilized by hydrogen bonding interactions with Lys822, which was different from other derivatives. In the further study, Compounds 43 and 44 had been synthesized and their biological activities were also evaluated, which were the same as that we expected. Compound 43 has demonstrated significant EGFR (IC(50)=0.12 µM) and tumor growth inhibitory activity as a potential anticancer agent.

Benzophenones from Guignardia sp. IFB-E028, an endophyte on Hopea hainanensis.

The first natural S-containing benzophenone dimer, named guignasulfide (3), was isolated from the culture of Guignardia sp. IFB-E028, an endophytic fungus residing in healthy leaves of Hopea hainanensis. Its structure was determined through correlative analyses of its MS, 1D- and 2D-NMR spectroscopic data. Two other known benzophenone derivatives, monomethylsulochrin and rhizoctonic acid (1 and 2, resp.) were also isolated. Guignasulfide (3) was more active against the human liver cancer cell line HepG2 (IC(50) value: 5.2+/-0.4 microM) than metabolites 1 and 2 (IC(50) values: 63.5+/-0.6 and 60.2+/-0.5 microM); compounds 1-3 showed also moderately inhibitory effects on the human bacterial pathogen Helicobacter pylori with MIC values of 28.9+/-0.1, 60.2+/-0.4, and 42.9+/-0.5 microM, respectively.

Structure and total synthesis of aspernigerin: a novel cytotoxic endophyte metabolite.

Aspernigerin (1), a novel cytotoxic alkaloid consisting of an unprecedented structural framework has been isolated from the extract of a culture of Aspergillus niger IFB-E003, an endophyte in Cyndon dactylon. Its structure was elucidated on the basis of comprehensive NMR spectral analysis and confirmed by single-crystal X-ray analysis. Aspernigerin (1) has been shown to be cytotoxic to the tumor cell lines nasopharynyeal epidermoid KB, cervical carcinoma Hela, and colorectal carcinoma SW1116 with corresponding IC(50) values of 22, 46, and 35 microM, respectively. A feasible total synthetic route for aspernigerin (1) has been established for further pharmacological research.