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.

Formation and functionalization of membraneless compartments in Escherichia coli.

Membraneless organelles formed by liquid-liquid phase separation of proteins or nucleic acids are involved in diverse biological processes in eukaryotes. However, such cellular compartments have yet to be discovered or created synthetically in prokaryotes. Here, we report the formation of liquid protein condensates inside the cells of prokaryotic Escherichia coli upon heterologous overexpression of intrinsically disordered proteins such as spider silk and resilin. In vitro reconstitution under conditions that mimic intracellular physiologically crowding environments of E. coli revealed that the condensates are formed via liquid-liquid phase separation. We also show functionalization of these condensates via targeted colocalization of cargo proteins to create functional membraneless compartments able to fluoresce and to catalyze biochemical reactions. The ability to form and functionalize membraneless compartments may serve as a versatile tool to develop artificial organelles with on-demand functions in prokaryotes for applications in synthetic biology.

Larvicidal activity of lignans from Phryma leptostachya L. against Culex pipiens pallens.

The larvicidal activity of crude petroleum ether, ethyl acetate, and methanol extracts of the whole plants of Phryma leptostachya L. was assayed for its toxicity against the early fourth instar larvae of Culex pipiens pallens. The larval mortality was observed after 24 h of exposure. Among three solvent extracts from Phyrma leptostachya L., the petroleum ether extract exhibited the best larvicidal activity. The corresponding LC50 values of petroleum ether, ethyl acetate, and methanol extracts were 3.23, 5.23, and 61.86 ppm against the early fourth instar larvae of Culex pipiens pallens. The petroleum ether extract was successively subjected to column chromatography and preparative high performance liquid chromatography, and yielded the three lignans, phrymarolin-I, haedoxane A, and haedoxane E, which were isolated and identified as new mosquito larvicidal compounds. Phrymarolin-I, haedoxane A, and haedoxane E showed high larvicidal activity, for which the lethal doses LC50 were estimated at 1.21, 0.025, and 0.15 ppm against the early fourth instar larvae of Culex pipiens pallens, respectively. The structures were elucidated by analyses of IR, UV, MS, and NMR spectral data. This is the first report on the mosquito larvicidal activity of the three compounds, phrymarolin-I, haedoxane A, and haedoxane E from Phyrma leptostachya L.

Microbial transformations of diosgenin by the white-rot basidiomycete Coriolus versicolor.

Microbial transformation of diosgenin (3ß-hydroxy-5-spirostene) using white-rot fungus Coriolus versicolor afforded four previously unreported polyhydroxylated steroids, 25(R)-spirost-5-en-3ß,7α,15α,21-tetraol (5), 25(R)-spirost-5-en-3ß,7ß,12ß,21-tetrol (6), (25R)-spirost-5-en-3ß,7α,12ß,21-tetraol (7), and (25R)-spirost-5-en-3ß,7ß,11α,21-tetraol (8), along with three known congeners, 25(R)-spirost-5-en-3ß,7ß-diol (2), 25(R)-spirost-5-en-3ß,7ß,21-triol (3), and 25(R)-spirost-5-en-3ß,7ß,12ß-triol (4). These structures were elucidated by 1D and 2D NMR as well as HR-ESIMS analysis. In addition, we provide evidence for two new microbial hydroxylations of diosgenin: C-21 primary carbon hydroxylation and C-15 hydroxylation. The 3ß-hydroxyl group and double bond in the B-ring of diosgenin were found to be important structural determinants for their activity.

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.

Chemical composition, antibacterial and antioxidant activity of the essential oil of Bupleurum longiradiatum.

The essential oil from the roots of Bupleurum longiradiatum, obtained by hydro-distillation was analyzed by gas chromatography/mass spectrometry (GC/MS) and evaluated for antimicrobial activity and antioxidant activity. Fifty-one compounds were identified, representing 99.3% of the total oil. The major constituents were thymol (7.0%), butylidene phthalide (6.8%), 5-indolol (5.6%), heptanal (5.3%), 4-hydroxy-2-methylacetophenone (5.3%), 4,5-diethyl-octane (5.3%), bormeol (5.1%) and hexanoic acid (5.1%). The oil was tested against 4 bacteria at different concentrations using disc diffusion and 96-well dilution methods. The inhibition zones and minimum inhibitory concentration values for bacterial strains were in the range of 7.0-18.0 mm and 250 -500 microg/mL, respectively. The in vitro antioxidant activity was assessed by DPPH radical scavenging and inhibition of lipid peroxidation methods. The oil showed a potent free radical scavenging activity, as evidenced by the low IC50 value for DPPH radical (566.2 microg/mL) and inhibition of lipid peroxidation (induced by FeSO4, H2O2 and CCl4) with IC50 values of 275.2 microg/mL, 296.9 microg/mL and 118.7 microg/mL, respectively.

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.