Jing-Li Cheng

Support vector machine (SVM) classification model based rational design of novel tetronic acid derivatives as potent insecticidal and acaricidal agents

A novel support vector machine (SVM) classification model was established for distinguishing potent and weak/inactive insecticides. Classification model-based rational design of novel tetronic acid derivatives was then performed to choose the preferable site of spirotetramat for chemical modification. Afterwards, eleven C5′-oxime ether-derived spirotetramat analogues, which are indicated as “potent class”, were synthesized and validated by biological assays, revealing that theoretical estimates are significantly consistent with experimental activities of these compounds. To be of interest, the most promising compound 91b exhibited excellent insecticidal and acaricidal activities. Moreover, molecular docking was further implemented to propose the possible interaction mode of acetyl-CoA carboxylase (ACCase) and compounds 91b, 91j, and 91k, providing some important and useful guidelines for further development.

Design, synthesis, and analysis of the quantitative structure-activity relationships of 4-phenyl-acyl-substituted 3-(2,5-dimethylphenyl)-4-hydroxy-1-azaspiro[4.5]dec-3-ene-2,8-dione derivatives.

A series of 4-phenyl-acyl-substituted 3-(2,5-dimethylphenyl)-4-hydroxy-1-azaspiro[4.5]dec-3-ene-2,8-dione derivatives were designed and synthesized, and their structures were characterized using (1)H NMR (or (13)C NMR), mass spectrometry, and elemental analysis. The bioactivities of the new compounds were evaluated. These compounds exhibited good inhibition activities against bean aphids (Aphis fabae) and carmine spider mite (Tetranychus cinnabarinus), and 4-phenyl acyl esters showed stronger bioactivity than 4-arylesterases and alkyl esters. The results showed that compound 8-I-e, which contains a para-methoxy group on the phenyl acyl, and compound 8-I-m, which contains a para-trifluoromethyl group on the phenyl acyl, displayed potent insecticidal activity against A. fabae and T. cinnabarinus respectively. The insecticidal activity showed a clear structure-activity relationship, confirming the importance of the flexible bridge. The DFT/B3LYP/6-31(d) level method was used to calculate molecular geometries and electronic descriptors. These factors included total energy, charge distribution, and the linear orbital level of the title compounds. Quantitative structure-activity relationship studies were performed on these compounds using quantum-chemical and physicochemical parameters as independent variables and insecticidal activity as a dependent variable. Insecticidal activity was most closely correlated (r > 0.8) with quantum chemical and physicochemical parameters.

Integration of pharmacophore mapping and molecular docking in sequential virtual screening: towards the discovery of novel JAK2 inhibitors

An integrated virtual screening protocol by combining molecular docking and pharmacophore mapping was established to identify novel inhibitors of JAK2 from a commercial compound database. Twelve novel and structurally diverse hits were selected and subjected to in vitro biological tests, and three compounds (A5, A6 and A9) with remarkable JAK2 inhibitory activity were identified. Then, the obtained structures were further used as the template for a subsequent similarity search, leading to the identification of another two promising compounds (B2 and B4). Selectivity profiles of JAK subtype and in vitro anti-cancer activity of the promising compounds were studied, revealing the promising compound B2 was of interest for further study because of its JAK2 selective profile, novelty of skeleton and significantly anti-proliferative effect against cancer cells. Finally, binding patterns of the compounds A5 and B2 were explored to provide a deeper insight for further structural optimization.

Metabolism-based synthesis, biological evaluation and structure-activity relationship analysis of spirotetramat analogues as potential lipid biosynthesis inhibitors.

BACKGROUND In previous studies, scientists found that, when spirotetramat was introduced into plants or animals, it was mainly metabolised at positions C-4 and C-8. That is to say, these two functional positions potentially played an important role in spirotetramats bioactivities. In order to develop novel insecticides or miticides, the present authors designed and synthesised 35 spirotetramat analogues based on metabolite structures. RESULTS All of the analogues have been identified on the basis of (1)H NMR, ESI-MS and elemental analysis data. The activities of these analogues were evaluated against three organisms, and biological assays indicated that compounds 5f, 5h and 5u possessed better insecticidal activities against bean aphids (Aphis fabae) than the lead compound spirotetramat. The LC50 of 5f, 5h and 5u against bean aphids reached 0.42, 0.28 and 2.53 mg L(-1) respectively. Moreover, some compounds possessed comparable activities against carmine spider mite (Tetranychus cinnabarinus) and oriental armyworm (Mythimna sepatara) with spirotetramat. The structure-activity relationships (SARs) indicated that the flexible bridge at position C-4 of spirotetramat was important for its bioactivities, and the size of the group at position C-8 would have great influence on the activities. Furthermore, the log P values lower than 6.0 may be favourable for insecticidal activities. CONCLUSION The present work demonstrates that some spirotetramat analogues can be used as potential lead compounds for developing novel insecticides, and preliminary SAR analysis would provide information for the utilisation of spirotetramat analogues as potential lipid biosynthesis inhibitors.

Optimization of pyrethroid and repellent on fabrics against Stegomyia albopicta (=Aedes albopictus) using a microencapsulation technique

A new approach employing a combination of pyrethroid and repellent is proposed to improve the protective efficacy of conventional pyrethroid‐treated fabrics against mosquito vectors. In this context, the insecticidal and repellent efficacies of commonly used pyrethroids and repellents were evaluated by cone tests and arm‐in‐cage tests against Stegomyia albopicta (=Aedes albopictus) (Diptera: Culicidae). At concentrations of LD50 (estimated for pyrethroid) or ED50 (estimated for repellent), respectively, the knock‐down effects of the pyrethroids or repellents were further compared. The results obtained indicated that deltamethrin and DEET were relatively more effective and thus these were selected for further study. Synergistic interaction was observed between deltamethrin and DEET at the ratios of 5 : 1, 2 : 1, 1 : 1 and 1 : 2 (but not 1 : 5). An optimal mixing ratio of 7 : 5 was then microencapsulated and adhered to fabrics using a fixing agent. Fabrics impregnated by microencapsulated mixtures gained extended washing durability compared with those treated with a conventional dipping method. Results indicated that this approach represents a promising method for the future impregnation of bednet, curtain and combat uniform materials.

Synthesis and Antifungal Activities of Trichodermin Derivatives as Fungicides on Rice

Twenty new trichodermin derivatives, 2a–5, containing alkoxy, acyloxy, and Br groups in 4‐, 8‐, 9‐, 10‐ and 16‐positions were synthesized and characterized. The antifungal activities of the new compounds against rice false smut (Ustilaginoidea virens), rice sheath blight (Rhizoctonia solani), and rice blast (Magnaporthe grisea) were evaluated. The results of bioassays indicated that the antifungal activities were particularly susceptible to changes at 4‐, 8‐, and 16‐positions, but low to changes at 9‐ and 10‐positions. Most of these target compounds exhibited good antifungal activities at the concentration of 50 mg l−1. Compound 4 (9‐formyltrichodermin; EC50 0.80 mg l−1) with an CHO group at 9‐position displayed nearly the same level of antifungal activity against Ustilaginoidea virens as the commercial fungicide prochloraz (EC50 0.82 mg l−1), while compound 3f ((8R)‐8‐{[(E)‐3‐phenylprop‐2‐enoyl]oxy}trichodermin; EC50 3.58 and 0.74 mg l−1) with a cinnamyloxy group at C(8) exhibited much higher antifungal activities against Rhizoctonia solani and Magnaporthe grisea than the commercial fungicides prochloraz (EC50 0.96 mg l−1) and propiconazole (EC50 5.92 mg l−1), respectively. These data reveal that compounds 3f and 4 possess high antifungal activities and may serve as lead compounds for the development of fungicides in the future.

Structure, bioactivity and implications for environmental remediation of complexes comprising the fungicide hexaconazole bound to copper

BACKGROUND In agricultural areas excessive amounts of toxic heavy metals are a growing threat to the environment and human health. Measures should be taken to minimise the risk of adverse health effects. Hence, we investigated the possibilities of hexaconazole (a commercial fungicidal) as a dual-function ligand that has heavy metal ions chelating and fungicidal activities. RESULTS Metal chelation and fungicidal activities were studied by UV, elemental analysis, IR, thermogravimetric study and biological assays. Results showed that hexaconazole had selective binding capability with Cu(2+) over other ions such as Zn(2+), Cd(2+), Mn(2+), Fe(2+) and Co(2+). Soil leaching experiments showed that soil type had a limited effect on heavy-metal adsorption by hexaconazole; with decreasing pH, a notable rise of leaching effect was observed, which reached 22%. In addition, this complex exhibit better fungicidal activity against Blumeria graminis than the same dose of hexaconazole. CONCLUSION This study demonstrates that hexaconazole had notable capabilities to chelate heavy metals as well as excellent fungicidal activity as a metal chelator. Given the mutual influence between pesticides and heavy metals in adsorption-desorption processes, these phenomena must be taken into account if they are to be applied rationally.

Synthesis and bioactivity evaluation of novel spiromesifen derivatives

BACKGROUND The development of environmentally friendly and novel structural pesticides is now an area of intense research in the agriculture field. Spirocyclic tetronic acids such as spiromesifen are typical compounds of this kind. In order to discover novel compounds with improved and broader-spectrum insecticidal activities, a series of spiromesifen derivatives were synthesised and bioassayed. RESULTS The derivatives were identified by (1) H NMR and MS. Preliminary bioassays demonstrated that some bioactivities of compounds 5a to 5u were better and had a broader spectrum than the lead compound spiromesifen. Moreover, these compounds showed better insecticidal activities against Mythimna sepatara and Aphis fabae than acaricidal activities against Tetranychus cinnabari. Furthermore, LC(50) of 5s against Aphis fabae reached 1.09 mg L(-1) . At the same time, compounds 5g, 5i, 5k and 5r also warrant further study because of their superior bioactivities to spiromesifen. What is more, suitable carbon chain length in the 4-position ester and the log P value of these spiromesifen derivatives dramatically influenced their insecticidal activities. Butyric or pentanoic ester and a log P value of 4.0-6.0 may be preferred. CONCLUSION The present work demonstrates that some spiromesifen derivatives can be used as potential lead compounds for developing novel insecticides and acaricides.

Trichodermol (4α-hydr­oxy-12,13-epoxy­trichothec-9-ene)

In the title compound, C15H22O3, the five-membered ring displays an envelope conformation, whereas the two six-membered rings show different conformations, viz. chair and half-chair. In the crystal, molecules are linked through intermolecular O—H⋯O hydrogen bonds, forming chains running along the b axis.

Design, Synthesis, and Fungicidal Evaluation of Novel Pyrazole-furan and Pyrazole-pyrrole Carboxamide as Succinate Dehydrogenase Inhibitors

The identification of novel succinate dehydrogenase (SDH) inhibitors represents one of the most attractive directions in the field of fungicide research and development. During our continuous efforts to pursue inhibitors belonging to this class, some structurally novel pyrazole-furan carboxamide and pyrazole-pyrrole carboxamide derivatives have been discovered via the introduction of scaffold hopping and bioisosterism to compound 1, a remarkably potent lead obtained by pharmacophore-based virtual screening. As a result of the evaluation against three destructive fungi, including Sclerotinia sclerotiorum, Rhizoctonia solani, and Pyricularia grisea, a majority of them displayed potent fungicidal activities. In particular, compounds 12I-i, 12III-f, and 12III-o exhibited excellent fungicidal activity against S. sclerotiorum and R. solani comparable to that of commercial SDHI thifluzamide and 1.