Synthesis and Herbicidal Activity of 2-(2-Oxo-3-pyridyl-benzothiazol-6-yloxy)hexanoic Acids.

The discovery of a lead compound is fundamental to herbicide innovation, but the limited availability of valuable lead compounds has hindered their development in recent years. By utilizing the structural diversity-oriented inactive group strategy, 3-(2-pyridyl)-benzothiazol-2-one was identified as a promising lead scaffold for herbicides, starting from benzothiazole which is an inactive moiety commonly found in herbicides such as mefenacet, benazolin, benzthiazuron, and fenthiaprop-ethyl. To investigate the structure-activity relationship (SAR) of these chemicals, a series of 2-(2-oxo-3-pyridyl-benzothiazol-6-yloxy)hexanoic acid derivatives () were synthesized through classical nucleophilic SAr reaction using halogenated pyridines and 6-methoxybenzothiazole-2-one.

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.

Synthesis and herbicidal activities of 2-((3-pyridinyl-2-oxo-2,3-dihydrobenzo[d]thiazol-6-yl)oxy)propionates.

Background: The discovery of lead compounds is fundamental to herbicide innovation, yet the limited availability of valuable lead compounds has impeded their progress in recent years. The study presents a novel molecular scaffold that exhibits remarkably potent herbicidal activity.

Results: Through a scaffold-hopping strategy, a highly potent lead compound for herbicides, namely 3-(2-pyridinyl)-benzothiazol-2-one, was unexpectedly discovered during attempts to structurally modify haloxyfop, a commercial aryl-oxy-phenoxy-propionate herbicide.

N-benzyl-2-methoxy-5-propargyloxybenzoamides, a new type of bleaching herbicides targeting the biosynthesis pathway of plastoquinone.

Background: Previously, the herbicidal activity of N-benzyl-2-methoxybenzamides was discovered during a random screening program in our laboratory. The chemicals resulted in bleaching effect of newly grown leaves by interfering with the biosynthesis of β-carotene in plant.

Results: A total of 28 benzamides were synthesized and subjected for the evaluation of herbicidal activity.

In vivo and in vitro antifungal activities of five alkaloid compounds isolated from Picrasma quassioides (D. Don) Benn against plant pathogenic fungi.

Highly active and novel antifungal compounds are continuously researched from natural products for pesticide development. Picrasma quassioides (D. Don) Benn, a species of Simaroubaceae, is used in traditional Chinese medicine to treat colds and upper respiratory infections.

Discovery of spirohydantoins as selective, orally bioavailable inhibitors of p300/CBP histone acetyltransferases.

p300 and CREB-binding protein (CBP) are essential for a multitude of cellular processes. Dysregulation of p300/CBP histone acetyltransferase activity is linked to a broad spectrum of human diseases including cancers. A novel drug-like spirohydantoin (21) has been discovered as a selective orally bioavailable inhibitor of p300/CBP histone acetyltransferase.

Discovery, SAR, and putative mode of action of N-benzyl-2-methoxybenzamides as potential bleaching herbicides.

Background: Herbicides acting on biosynthesis of plant pigments have contributed greatly to weed control in recent years. In our previous studies, 2-methoxybenzamides were discovered as a novel type of lead compound for the development of bleaching herbicides.

Results: A total of 67 benzamide analogues were synthesized and evaluated for herbicidal activity.

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

Based on the structures of isoxaflutole (IFT) and -isobutyl--(4-chloro-benzyl)-4-chloro-2-pentenamide, a series of -benzyl-5-cyclopropyl-isoxazole-4-carboxamides was designed by connecting their pharmacophores (, a multitarget drug design strategy). A total of 27 -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 showed 100% inhibition against and at a concentration of 10 mg/L, better than the positive control butachlor (50% inhibition for both weeds).

Identification and mechanism of insecticidal periplocosides from the root bark of Periploca sepium Bunge.

Background: The Periploca sepium bark root (PSBR) has been regarded as a potential botanical insecticide because of its significant insecticidal activity of secondary metabolites. Several periplocosides were isolated from it as promising pesticides to control crop pests in agriculture.

Results: In our research, two new periplocosides, along with four known periplocosides were isolated from PSBR.

Investigation on the Antifungal Ingredients of Hhs.015, an Antagonistic Endophytic Actinomycete Isolated from Cucumber Plant.

A Apple tree canker infected by Valsa mali var is a serious and widely distributed disease in China. Hhs.015 is an endophytic actinomycete isolated from cucumber roots, and it has been proven that this strain is a promising biocontrol agent on apple tree canker in previous studies.

Synthesis, antifungal and antitumor activity of two new types of imidazolin-2-ones.

Thirty-six imidazolin-2-ones, including ten pairs of benzimidazolones and sixteen imidazopyridines, were synthesized and subjected for the evaluation of antifungal and antitumor activity. Compounds 4a-01, 6-01, 6-04 and 6-06 could effectively inhibit the spore germination and mycelium growth of Botrytis cinerea. The relationship between structure and antifungal activity revealed that the introducing short-chain aliphatic acyl groups at the moiety of imidazopyridines is favorable for the antifungal activity, whereas aromatic acyl groups are much better than aliphatic acyl groups for the activity of benzimidazolones except for acetyl.

SAR of amino pyrrolidines as potent and novel protein-protein interaction inhibitors of the PRC2 complex through EED binding.

Herein we disclose SAR studies of a series of dimethylamino pyrrolidines which we recently reported as novel inhibitors of the PRC2 complex through disruption of EED/H3K27me3 binding. Modification of the indole and benzyl moieties of screening hit 1 provided analogs with substantially improved binding and cellular activities. This work culminated in the identification of compound 2, our nanomolar proof-of-concept (PoC) inhibitor which provided on-target tumor growth inhibition in a mouse xenograft model.

Structure and Antibacterial Activity of Ambobactin, a New Telomycin-Like Cyclic Depsipeptide Antibiotic Produced by Streptomyces ambofaciens F3.

A new telomycin-like cyclic depsipeptide, ambobactin (1), was isolated from the metabolites of Streptomyces ambofaciens F3, an endophyte of Platycladus orientalis. Its structure was elucidated on the basis of extensive spectroscopic analysis and advanced Marfey's method. Ambobactin is structurally related with telomycin, except that the configuration of the 3-methyltryptophanes in their structures is different.

Synthesis and herbicidal activities of benzothiazole N,O-acetals.

A new series of N,O-acetals were prepared via a simple one-pot reaction by the condensation of 2-amino-methybenzothiazole with aldehydes and alcohols. The title compounds were obtained in moderate to good yields in the presence of acid catalyst. Bioassay results indicated that some synthesized compounds had good herbicidal activity against both dicotyledon and monocotyledon weeds.

[Identification of a kojic-acid producing Aspergillus flavus F52].

Objective: We identified an endophytic fungus of Vigna unguiculata, as well as the influence of carbon sources on the production of kojic acid by the isolated fungus.

Methods: This kojic acid producer was identified as Aspergillus flavus F52 according to morphological characteristics and ITS region of rDNA. The metabolite of strain F52 was obtained by recrystallization, and identified as kojic acid based on the spectral data of NMR, HR-ESI/MS and IR.

[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.

Synthesis of 1-isopropyl-3-acyl-5-methyl-benzimidazolone derivatives and their antimicrobial activity.

A series of N-acylated analogues of 1-isopropyl-3-acyl-5-methyl-benzimidazolone were synthesized. Bioassay results indicated that analogues 5-07 and 5-19 exhibited the most potency against Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Analogues 5-02, 5-07, 5-12, 5-15, 5-19, 5-20 and 5-25 could effectively inhibit the spore germination of Botrytis cinerea.

Identification of pyrroloindoline-containing cyclic hexapeptides in the metabolites of Streptomyces alboflavus 313 by HPLC-DAD-ESI-MS/MS.

To investigate the chemical biodiversity of biologically active cyclic hexapeptides in the metabolites from microorganisms, the fermentation broth of Streptomyces alboflavus 313 was analyzed using HPLC, equipped with a diode array detector (DAD), coupled with ESI tandem MS (HPLC-DAD-ESI-MS/MS). In the mass spectra of cyclic hexapeptides, predominant ions [M+H](+), as well as [M-18+H](+), [M-28+H](+) and [M+Na](+), were observed and used to determine the molecular masses, while fragmentation reactions of [M+H](+) were recorded to provide information on the contents of amino acids and their linkage sequence. Based on the fragmentation patterns and comparison with standards, 15 pyrroloindoline-containing natural cyclic hexapeptides, cp01-15, were identified from the microorganism and six of these are reported for the first time.

Isolation and characterization of two novel antibacterial cyclic hexapeptides from Streptomyces alboflavus 313.

Two novel cyclic hexapeptides, designated NW-G08 (1) and NW-G09 (2), were isolated from the fermentation broth of Streptomyces alboflavus 313. Their structures were elucidated on the basis of extensive spectroscopic analysis, MS experiments, and chemical analysis. Their antibacterial activities against several strains of bacteria were evaluated by micro-broth dilution method.

New antifungal pyranoisoflavone from Ficus tikoua Bur.

Considering the undesirable attributes of synthetic fungicides and the availability of Ficus species in China, the stem of Ficus tikoua Bur. was investigated. One new antifungal pyranoisoflavone, 5,3',4'-trihydroxy-2″,2″-dimethylpyrano (5″,6″:7,8) isoflavone (1), together with two known isoflavones, wighteone (2) and lupiwighteone (3) (with previously reported antifungal activities), were isolated from ethyl acetate extract by bioassay-guided fractionation.

Exploration of diverse hinge-binding scaffolds for selective Aurora kinase inhibitors.

Four hinge-binding scaffolds have been explored for novel selective Aurora kinase inhibitors. The structure activity relationship, selectivity and pharmacokinetic profiles have been evaluated.

Enhanced production of a novel cyclic hexapeptide antibiotic (NW-G01) by Streptomyces alboflavus 313 using response surface methodology.

NW-G01, produced by Streptomyces alboflavus 313, is a novel cyclic hexapeptide antibiotic with many potential applications, including antimicrobial activity and antitumor agents. This study developed a system for optimizing medium components in order to enhance NW-G01 production. In this study, Plackett-Burman design (PBD) was used to find the key ingredients of medium components, and then response surface methodology (RSM) was implemented to determine their optimal concentrations.

Synthesis and antibacterial activities of 1-alkyl-3-methacryloyl (acryloyl) of benzimidazolone (thione) derivatives.

A series of (28) 1-alkyl-3-methacryloyl (acryloyl)-benzimidazolone (thione) deriv-atives were synthesized. The structures of the new derivatives were confirmed by (1)H-NMR, (13)C-NMR and ESI-MS spectral analysis. The antibacterial activities of these compounds against several strains of bacteria, such as Bacillus cereus, Bacillus subtilis, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, were evaluated by methods of paper disc-diffusion and broth mciro-dilution.

Two piperazic acid-containing cyclic hexapeptides from Streptomyces alboflavus 313.

Two novel cyclic hexapeptides, designated NW-G10 (1) and NW-G11 (2), were isolated from the fermentation broth of Streptomyces alboflavus 313. Their relative structures were elucidated on the basis of extensive spectroscopic analysis, and the absolute configurations of several constituent amino acids were determined by Marfey's method. NW-G10 (1) and NW-G11 (2) exhibited significant activity against Gram-positive bacteria, such as Bacillus cereus, Bacillus subtilis and Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA), but they are not active against gram negatives.

Three novel cyclic hexapeptides from Streptomyces alboflavus 313 and their antibacterial activity.

Three novel cyclic hexapeptides, designated NW-G05 (1), NW-G06 (2) and NW-G07 (3), were isolated from the fermentation broth of Streptomyces alboflavus 313. Their structures were elucidated on the basis of extensive spectroscopic analysis, MS experiments, and chemical analysis. Their antibacterial activities against several strains of bacteria were evaluated by micro-broth dilution method.