Discovery of N-benzyl-6-methylpicolinamide as a potential scaffold for bleaching herbicides.

BACKGROUND: In pesticide research, bleaching herbicides have always been a hot topic. Our previous research showed that N-(4-fluorobenzyl)-2-methoxybenzamide is an innovative lead compound for bleaching herbicides. RESULTS: A total of 40 derivatives of picolinamides were prepared and evaluated for their herbicidal activity by Petri dish tests and postemergence trials. The structure-activity relationship (SAR) revealed that introducing electron-withdrawing groups at the 3- or 4-positions of the benzyl significantly enhances herbicidal activity. Furthermore, ZI-04 induced similar symptoms such as bleaching effect in treated weeds and accumulation of biosynthetic precursors for carotenoids as observed with diflufenican. ZI-04 also exhibited significant cross-resistance to diflufenican and had a lower resistance risk than diflufenican. CONCLUSION: N-benzyl-6-methylpicolinamides were discovered as a novel scaffold for bleaching herbicides. The accumulation of phytoene, phytofluene and ζ-Carotene in radish cotyledons, and cross-resistance observed with diflufenican, showed that title compounds can interfere with carotenoid biosynthesis. © 2024 Society of Chemical Industry.

Design, Synthesis, and Herbicidal Activity of N-Benzyl-5-cyclopropyl-isoxazole-4-carboxamides.

Based on the structures of isoxaflutole (IFT) and N-isobutyl-N-(4-chloro-benzyl)-4-chloro-2-pentenamide, a series of N-benzyl-5-cyclopropyl-isoxazole-4-carboxamides was designed by connecting their pharmacophores (i.e., a multitarget drug design strategy). A total of 27 N-benzyl-5-cyclopropyl-isoxazole-4-carboxamides were prepared from 5-cyclopropylisoxazole-4-carboxylic acid and substituted benzylamines, and their structures were confirmed by NMR and MS. Laboratory bioassays indicated that I-26 showed 100% inhibition against Portulaca oleracea and Abutilon theophrasti at a concentration of 10 mg/L, better than the positive control butachlor (50% inhibition for both weeds). A strong growth inhibition was observed, but a typical bleaching phenomenon of IFT could not be observed in the Petri dish assay. I-05 displayed excellent postemergence herbicidal activity against Echinochloa crusgalli and A. theophrasti at a rate of 150 g/ha, and bleaching symptoms were observed in the leaves of treated weeds. The bleaching effect of Chlamydomonas reinhardtii treated by I-05 could be reversed by adding homogentisate. Enzymatic bioassays indicated that I-05 could not inhibit 4-hydroxyphenylpyruvate dioxygenase (HPPD) activity, but II-05, an isoxazole ring-opening product of I-05, could inhibit HPPD activity with an EC50 value of 1.05 µM, similar to that of mesotrione (with an EC50 value of 1.35 µM). Detailed discussion about observed herbicidal symptoms is provided in the Results and Discussion section. This investigation provided a proof-of-concept foundation that a multitarget drug design strategy could be applied in agrochemical research.

[Treatment of premature ovarian failure patients of Shen Yang deficiency syndrome by warming Shen, enhancing Yang, invigorating qi, and nourishing blood method combined artificial cycle therapy: a clinical observation].

OBJECTIVE: To observe the clinical efficacy of warming Shen, enhancing Yang, invigorating qi, and nourishing blood method (WSEYIQNBM) combined artificial cycle therapy in treatment of premature ovarian failure (POF) patients of Shen yang deficiency syndrome (SYDS). METHODS: Totally 96 POF patients of SYDS were randomly assigned to the treatment group and the control group, 48 in each group. Patients in the treatment group were treated with WSEYIQNBM combined artificial cycle therapy, while those in the control group were treated with Western medicine artificial cycle therapy. One month constituted 1 course, a total of 3 courses. The menstruation and main symptoms were observed before and after treatment. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were detected before and after treatment. RESULTS: The total effective rate was 85.43% in the treatment group, higher than that of the control group (79.17%, P < 0.05). Besides, better effect in improving Chinese medical symptoms was obtained in the treatment group (P < 0.05). CONCLUSION: POF patients' serum hormone levels and clinical symptoms could be improved by WSEYIQNBM combined artificial cycle therapy.

A new benzofuran glucoside from Ficus tikoua Bur.

From the water-soluble portion of the methanol extract of stems of Ficus tikoua Bur., a new benzofuran glucoside, named 6-carboxyethyl-5-hydroxybenzofuran 5-O-ß-d-glucopyranoside (1), together with one known benzofuran glucoside (2) were isolated. Their structures were elucidated by 1D and 2D ((1)H-(1)H COSY, HMQC, and HMBC) NMR spectroscopy and HRMS techniques. The antioxidant activities of the isolated compounds were assayed based on the scavenging activities of DPPH free radical. Compounds 1 and 2 exhibited moderate antioxidant activities, and the IC(50) values were 242.8 µg·mL(-1) and 324.9 µg·mL(-1), respectively.

Isolation, biological evaluation and 3D-QSAR studies of insecticidal/narcotic sesquiterpene polyol esters.

For the first time, a set of (43) natural sesquiterpene polyol esters isolated from the root bark of Celastrus angulatus Maxim and Euonymus japonicus Thunb were subjected to 3D-QSAR comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) studies, with the aim of proposing novel sesquiterpene-based compounds with optimal narcotic or insecticidal activities. The established 3D-QSAR models exhibit reasonable statistical quality and prediction capabilities, with internal cross-validated Q (2) values of ∼ 0.5 and external predicted R (2) values of >0.9, respectively. The relative contributions of the steric/electrostatic fields of the 3D-QSAR models show that the electronic effect governs the narcotic activities of the molecules, but the hybrid effect of the electrostatic and hydrophobic interactions is more influential in the insecticidal activities of the compounds. These findings may have valuable implications for the development of novel natural insecticides.

Synthesis of 1-acyl-3-isopropenylbenzimidazolone derivatives and their activity against Botrytis cinerea.

A series of 1-acyl-3-isopropenylbenzimidazolone derivatives were synthesized, and their structures were characterized by (1)H and (13)C NMR and elemental analysis. Their fungicidal activities against Botrytis cinerea were also evaluated by spore germination assay. The acrylic acid, methacrylic acid, 4-chlorophenyl acetic acid, and 2-chlorobenzoic acid derivatives exhibited strong fungicidal activity. This implied that benzimidazolones might be potential fungicide leading compounds.

A new insecticidal sesquiterpene ester from Celastrus angulatus.

A new sesquiterpene polyol ester with a beta-dihydroagarofuran skeleton, NW37 (1), and three known compounds NW13 (2), NW16 (3) and NW35 (4) were isolated by bioassay-guided fractionation from the highly polar MeOH extracts of the root bark of Celastrus angulatus. Their chemical structures were elucidated mainly by analyses of MS and NMR spectral data. The insecticidal activity of compound 1 against 4th instar Mythimna separata larvae with a KD(50) value of 252.3 microg g(-1) was demonstrated.