Synthesis and Pesticidal Activities of New Quinoxalines.

Natural products are a source of many novel compounds with biological activity for the discovery of new pesticides and pharmaceuticals. Quinoxaline is a fused N-heterocycle in many natural products and synthetic compounds, and seven novel quinoxaline derivatives were designed and synthesized via three steps. Pesticidal activities of title quinoxaline derivatives were bioassayed. Most of these compounds had herbicidal, fungicidal, and insecticidal activities. The compounds 2-(6-methoxy-2-oxo-3-phenylquinoxalin-1(2H)-yl)acetonitrile (3f) and 1-allyl-6-methoxy-3-phenylquinoxalin-2(1H)-one (3g) were the most active herbicides and fungicides. Mode-of-action studies indicated that 3f is a protoprophyrinogen oxidase-inhibiting herbicide. Compound 3f also possessed broad-spectrum fungicidal activity against the plant pathogen Colletotrichum species. Some of these compounds also had insecticidal activity. Molecular docking and DFT analysis can potentially be used to design more active compounds.

Novel 4-pyrazole carboxamide derivatives containing flexible chain motif: design, synthesis and antifungal activity.

BACKGROUND: In recent years, carboxamide fungicides, targeting succinate dehydrogenase (SDH), have shown highly efficient and broad spectrum fungicidal activity. Structure-activity relationship (SAR) results for these commercial fungicides show that the carboxamide group was a key active group. This is useful information for the discovery of new pyrazole carboxamide derivatives with fungicidal activity. RESULTS: Twenty-seven novel pyrazole carboxamides were designed and synthesized. Their fungicidal activities against Gibberella zeae, Phytophthora infestans, Phytophthora capsici, Rhizoctonia solani, Alternaria solani, Botrytis cinerea, Fusarium oxysporum, Cercospora arachidicola, Sclerotinia sclerotiorum and Physalospora piricola were tested; derivatives possessed excellent inhibitory at 50 mg L-1 in particular. Furthermore, some pyrazole carboxamides exhibited remarkably high activities against Sclerotinia sclerotiorum in vitro with EC50 values of 2.04 to 15.2 µg mL-1 . In addition, some compounds also exhibited high activities against Physalospora piricola, Cercospora arachidicola and Phytophthora capsici. Inhibition activities against SDH proved that the designed analogues were effective at the enzyme level. The SAR of these pyrazole carboxamides was studied by using the docking method. CONCLUSION: It is possible that pyrazole carboxamides, which exhibit good activity against Sclerotinia sclerotiorum, can be further optimized as a lead compounds of carboxamide fungicides. © 2019 Society of Chemical Industry.

Microwave assisted synthesis, antifungal activity, DFT and SAR study of 1,2,4-triazolo[4,3-a]pyridine derivatives containing hydrazone moieties.

BACKGROUND: The increasing prevalence of multi-drug resistant fungal infections has encouraged the search for new antifungal agents. Hydrazone derivatives always exhibited diversity activities, including antifungal, anti-inflammatory, anti-oxidation, anti-cancer activity. Regarding the heterocyclic moiety, 1,2,4-triazolo[4,3-a]pyridine derivatives also display broad activities, such as antifungal activity, anticonvulsant activity, herbicidal activity, antimicrobial activity and anticancer activity. RESULTS: A series of novel 1,2,4-triazolo[4,3-a]pyridine derivatives containing hydrazone moiety were designed and synthesized from 2,3-dichloropyridine, hydrazine hydrate by multi-step reactions under microwave irradiation condition, and their structures were characterized by FT IR, (1)H NMR, (13)C NMR, (19)F NMR, MS and elemental analysis. The antifungal activities of title compounds were determined. The results indicated that some of the title compounds exhibited good antifungal activity. Furthermore, DFT calculation was carried out for studying the structure-activity relationship (SAR). CONCLUSION: A practical synthetic route to obtain 1,2,4-triazolo[4,3-a]pyridine derivatives is presented. This study suggests that the 1,2,4-triazolo[4,3-a]pyridine derivatives exhibited good antifungal activity.

pH-Dependence of the Aqueous Phase Room Temperature Brønsted Acid-Catalyzed Chemoselective Oxidation of Sulfides with H2O2.

A pH-dependence of the Brønsted acid-catalyzed oxidation of sulfides to the corresponding sulfoxides with H2O2 is reported for the first time based on our systematic investigation of the catalytic performance of a series of Brønsted acids. For all of the Brønsted acids investigated, the catalytic performances do not depend on the catalyst loading (mol ratio of Brønsted acid to substrate), but rather depend on the pH value of the aqueous reaction solution. All of them can give more than 98% conversion and selectivity in their aqueous solution at pH 1.30, no matter how much the catalyst loading is and what the Brønsted acid is. This pH-dependence principle is a very novel perspective to understand the Brønsted-acid catalysis system compared with our common understanding of the subject.

Apigenin inhibits TGF-ß1-induced proliferation and migration of airway smooth muscle cells.

It is well known that the proliferation and migration of ASM cells (ASMCs) plays an important role in the pathogenesis of airway remodeling in asthma. Previous studies reported that apigenin can inhibit airway remodeling in a mouse asthma model. However, its effects on the proliferation and migration of ASMCs in asthma remain unknown. Therefore, the aim of our present study was to investigate the effects of apigenin on ASMC proliferation and migration, and explore the possible molecular mechanism. We found that apigenin inhibited transforming growth factor-ß1 (TGF-ß1)-induced ASMC proliferation. The cell cycle was blocked at G1/S-interphase by apigenin. It also suppressed TGF-ß1-induced ASMCs migration. Furthermore, apigenin inhibited TGF-ß1-induced Smad 2 and Smad 3 phosphorylation in ASMCs. Taken together, these results suggested that apigenin inhibited the proliferation and migration of TGF-ß1-stimulated ASMCs by inhibiting Smad signaling pathway. These data might provide useful information for treating asthma and show that apigenin has potential for attenuating airway remodeling.

Microwave assistant synthesis, antifungal activity and DFT theoretical study of some novel 1,2,4-triazole derivatives containing pyridine moiety.

In order to investigate the biological activity of novel 1,2,4-triazole compounds, seventeen novel 1,2,4-triazole derivatives containing pyridine moiety were synthesized under microwave assistant condition by multi-step reactions. The structures were characterized by 1H NMR, MS and elemental analyses. The target compounds were evaluated for their fungicidal activities against Stemphylium lycopersici (Enjoji) Yamamoto, Fusarium oxysporum. sp. cucumebrium, and Botrytis cinerea in vivo, and the results indicated that some of the title compounds displayed excellent fungicidal activities. Theoretical calculation of the title compound was carried out with B3LYP/6-31G (d,p). The full geometry optimization was carried out using 6-31G (d,p) basis set, and the frontier orbital energy, atomic net charges were discussed, and the structure-activity relationship was also studied.