Design, Synthesis, Characterization, and Insecticidal Bioefficacy Screening of Some New Pyridine Derivatives.

A lot of insecticides are found nowadays, but neonicotinoids are considered the most famous. So, a series of pyridine derivatives neonicotinoids analogues, namely, 3-cyano-4,6-dimethylpyridine-2(1H)-one (1), 2-chloro-3-cyano-4,6-dimethylpyridine (2), 3-cyano-4,6-dimethylpyridine-2(1H)-thione (3), 3-cyano-4,6-distyrylpyridine-2(1H)-thione (4), 2-((3-cyano-4,6-distyrylpyridin-2-yl)thio)-N-phenylacetamide (5), 3-amino-N-phenyl-4,6-distyrylthieno[2,3-b]pyridine-2-carboxamide (6), 2-((3-cyano-4,6-distyrylpyridin-2-yl)thio)-N-(p-tolyl)acetamide (7), 3-amino-4,6-distyryl-N-(p-tolyl)thieno[2,3-b]pyridine-2-carboxamide (8), 2-((3-cyano-4,6-distyrylpyridin-2-yl)thio)-N-(4-methoxyphenyl)acetamide (9), and 3-amino-N-(4-methoxyphenyl)-4,6-distyrylthieno[2,3-b]pyridine-2-carboxamide (10), have been designed and synthesized in pure state, and their agricultural bioefficacy as insecticides against cowpea aphid Aphis craccivora Koch was screened. The structures of the synthesized compounds were verified by means of spectroscopic and elemental analyses. Insecticidal bioefficacy data illustrated that some compounds are excellent against cowpea aphid, and the bioefficacy of the rest of the tested compounds ranged from good to moderate against the same insects.

Chemical design and toxicity evaluation of new pyrimidothienotetrahydroisoquinolines as potential insecticidal agents.

Neonicotinoids are the most widely used from all existing pesticides. So, in purpose to discover new pesticides being more effective against the aphid, twelve heterocyclic compounds neonicotinoid analogs have been prepared in a pure state; pyrimidothienotetrahydroisoquinolines 1-12 and their toxicity as potential insecticidal agents against cowpea Aphid, Aphis craccivora Koch was screened. Their characterizations by using spectroscopic analyses were performed. The toxicity data exhibited that the 8-chloropyrimidine compound 4 is more toxic about 2-fold than a reference insecticide, acetamiprid. The other screened compounds showed weak to strong toxicological activities against cowpea aphid.

Subchronic exposure to sublethal dose of imidacloprid changes electrophysiological properties and expression pattern of nicotinic acetylcholine receptor subtypes in insect neurosecretory cells.

Neonicotinoids are the most important class of insecticides used in agriculture over the last decade. They act as selective agonists of insect nicotinic acetylcholine receptors (nAChRs). The emergence of insect resistance to these insecticides is one of the major problems, which limit the use of neonicotinoids. The aim of our study is to better understand physiological changes appearing after subchronic exposure to sublethal doses of insecticide using complementary approaches that include toxicology, electrophysiology, molecular biology and calcium imaging. We used cockroach neurosecretory cells identified as dorsal unpaired median (DUM) neurons, known to express two α-bungarotoxin-insensitive (α-bgt-insensitive) nAChR subtypes, nAChR1 and nAChR2, which differ in their sensitivity to imidacloprid. Although nAChR1 is sensitive to imidacloprid, nAChR2 is insensitive to this insecticide. In this study, we demonstrate that subchronic exposure to sublethal dose of imidacloprid differentially changes physiological and molecular properties of nAChR1 and nAChR2. Our findings reported that this treatment decreased the sensitivity of nAChR1 to imidacloprid, reduced current density flowing through this nAChR subtype but did not affect its subunit composition (α3, α8 and ß1). Subchronic exposure to sublethal dose of imidacloprid also affected nAChR2 functions. However, these effects were different from those reported on nAChR1. We observed changes in nAChR2 conformational state, which could be related to modification of the subunit composition (α1, α2 and ß1). Finally, the subchronic exposure affecting both nAChR1 and nAChR2 seemed to be linked to the elevation of the steady-state resting intracellular calcium level. In conclusion, under subchronic exposure to sublethal dose of imidacloprid, cockroaches are capable of triggering adaptive mechanisms by reducing the participation of imidacloprid-sensitive nAChR1 and by optimizing functional properties of nAChR2, which is insensitive to this insecticide.

The Repellent DEET Potentiates Carbamate Effects via Insect Muscarinic Receptor Interactions: An Alternative Strategy to Control Insect Vector-Borne Diseases.

Insect vector-borne diseases remain one of the principal causes of human mortality. In addition to conventional measures of insect control, repellents continue to be the mainstay for personal protection. Because of the increasing pyrethroid-resistant mosquito populations, alternative strategies to reconstitute pyrethroid repellency and knock-down effects have been proposed by mixing the repellent DEET (N,N-Diethyl-3-methylbenzamide) with non-pyrethroid insecticide to better control resistant insect vector-borne diseases. By using electrophysiological, biochemichal, in vivo toxicological techniques together with calcium imaging, binding studies and in silico docking, we have shown that DEET, at low concentrations, interacts with high affinity with insect M1/M3 mAChR allosteric site potentiating agonist effects on mAChRs coupled to phospholipase C second messenger pathway. This increases the anticholinesterase activity of the carbamate propoxur through calcium-dependent regulation of acetylcholinesterase. At high concentrations, DEET interacts with low affinity on distinct M1/M3 mAChR site, counteracting the potentiation. Similar dose-dependent dual effects of DEET have also been observed at synaptic mAChR level. Additionally, binding and in silico docking studies performed on human M1 and M3 mAChR subtypes indicate that DEET only displays a low affinity antagonist profile on these M1/M3 mAChRs. These results reveal a selective high affinity positive allosteric site for DEET in insect mAChRs. Finally, bioassays conducted on Aedes aegypti confirm the synergistic interaction between DEET and propoxur observed in vitro, resulting in a higher mortality of mosquitoes. Our findings reveal an unusual allosterically potentiating action of the repellent DEET, which involves a selective site in insect. These results open exciting research areas in public health particularly in the control of the pyrethroid-resistant insect-vector borne diseases. Mixing low doses of DEET and a non-pyrethroid insecticide will lead to improvement in the efficiency treatments thus reducing both the concentration of active ingredients and side effects for non-target organisms. The discovery of this insect specific site may pave the way for the development of new strategies essential in the management of chemical use against resistant mosquitoes.

Pyridine derivatives as insecticides. Part 1: synthesis and toxicity of some pyridine derivatives against cowpea aphid, Aphis craccivora Koch (Homoptera: Aphididae).

Five pyridine derivatives, namely, N-morpholinium 7,7-dimethyl-3-cyano-4-(4'-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-2-thiolate (1), sodium 5-acetyl-3-amino-4-(4'-methoxyphenyl)-6-methylthieno[2,3-b] pyridine-2-carboxylate (2), piperidinium 3,5-dicyano-2-oxo-4-spirocyclopentane-1,2,3,4-tetrahydropyridine-6-thiolate (3), piperidinium 5-acetyl-3-cyano-4-(4'-methoxyphenyl)-6-methylpyridine-2-thiolate (4), and piperidinium 5-acetyl-4-(4'-chlorophenyl)-3-cyano-6-methyl-pyridine-2-thiolate (5) were prepared in pure state and subjected to the title study. The bioassay results indicated that the insecticidal activity of compound 1 is about 4-fold that of acetamiprid insecticide. The rest of the tested compounds possess moderate to strong aphidicidal activities.