Effect of Novaluron (Rimon 10 EC) on the mosquitoes Anopheles albimanus, Anopheles pseudopunctipennis, Aedes aegypti, Aedes albopictus and Culex quinquefasciatus from Chiapas, Mexico

Dengue fever is a serious problem in Mexico and vector control has not been effective enough at preventing outbreaks. Malaria is largely under control, but it is important that new control measures continue to be developed. Novaluron, a novel host-specific insect growth regulator and chitin synthesis inhibitor, has proved to be effective against agricultural pests, but its efficacy against larval mosquito vectors under field conditions remains unknown. In accordance with the World Health Organization Pesticide Evaluation Scheme, phase I, II and III studies were conducted to evaluate the efficacy and residual effect of Novaluron (Rimon 10 EC, Makhteshim, Beer-Sheva, Israel) on the malaria vectors Anopheles albimanus Wiedemann (Diptera: Culicidae) and Anopheles pseudopunctipennis Theobald, the dengue vectors Aedes aegypti (L) and Aedes albopictus Skuse and the nuisance mosquito Culex quinquefasciatus Say. Laboratory susceptibility tests yielded diagnostic concentrations for all five target species. Field trials to identify the optimum field dosage of Novaluron against Anopheles mosquitoes were carried out under semi-natural conditions in artificial plots and in vessels with wild mosquitoes. Efficacy was measured by monitoring mortality of larvae and pupae and the percentage of inhibition of emergence from floating cages. Dosages of Novaluron for field tests were based on pupal LC(99) (lethal concentration 99%) of An. pseudopunctipennis (0.166 mg/L) in plots and average pupal LC(99) of Ae. aegypti and Ae. albopictus (0.55 mg/L). At all dosages tested, Novaluron significantly reduced larval populations of An. albimanus, Culex coronator Dyar & Knab, Ae. albopictus and Cx. quinquefasciatus by approximately 90%, inhibited adult emergence of An. albimanus and An. pseudopunctipennis by approximately 97% for almost 4 months in experimental plots, and inhibited adult emergence of Ae. aegypti and Ae. albopictus by approximately 97% for up to 14 weeks. Recommended dosages of Novaluron for non-container breeding and container breeding mosquitoes are 0.166 mg/L and 0.55 mg/L, respectively. Overall, the residual effect was more sustained than that of temephos. The lowest dosage of Novaluron had less of an impact on non-target organisms than did temephos. Small-scale field trials in natural breeding sites treated with Novaluron at 0.6 L/ha eliminated adult emergence of An. albimanus and Cx. coronator for 8 weeks. For phase III studies, Novaluron was tested at the local and village levels, applying the optimum field rate to all natural breeding habitats within 1 km of a pair of neighbouring villages. Village-scale trials of Novaluron at 0.6 L/ha reduced An. albimanus larval populations for at least 8 weeks and, more importantly, sharply reduced the densities of adult host-seeking mosquitoes approaching houses. We conclude that Novaluron is effective and environmentally safer than temephos.     

Pyridalyl, a novel insecticide: potency and insecticidal selectivity

Pyridalyl is an insecticide of a novel chemical class (unclassified insecticides). Toxicity of pyridalyl to two insect pest species, Spodoptera litura and Frankliniella occidentalis, an insect predator, Orius stringicollis, and a pollinator, Bombus terrestris, was evaluated in the laboratory. The insecticidal activity of pyridalyl against S. litura was evaluated using the leaf-dipping method. The potency of pyridalyl was highly effective against all development stages (2nd to 6th instar larvae) of S. litura. This compound was also evaluated against F. occidentalis using the direct spray method. For F. occidentalis, toxicity of pyridalyl was almost similar to that of acrinathrin, but greater than acrinathrin for adults. Then the toxicity of this product to the natural enemies, Orius stringicollis and the pollinating insect Bombus terrestris, was evaluated using the body-dipping method or direct spray method. No acute toxicity of this product was observed on these non-target insects. Moreover, the influence of pyridalyl to the nest of Bombus terrestris was evaluated using the direct spray to the inside of the nest. No apparent influence of this compound was observed by 21 days after treatment. The cytotoxicity of pyridalyl to the Sf9 insect cell line and the CHO-K1 mammalian cell line was evaluated using the trypan-blue exclusion method. High toxicity to the insect cell line, but almost no toxicity to the mammalian cell line, was observed. Thus, pyridalyl exhibited high selectivity in cytotoxicity between the insect and mammalian cell line as well as in insecticidal activity among insect species. We infer pyridalyl may be useful for IPM programs of greenhouse cultivation system.     

Insecticides with novel modes of action: Mechanism, selectivity and cross-resistance

Efforts have been made during the past two decades to develop insecticides with selective properties that act specifically on biochemical sites present in particular insect groups, but whose properties differ from other insecticides. This approach has led to the discovery of compounds that affect the hormonal regulation of molting and developmental processes in insects; for example, ecdysone agonists, juvenile hormone mimics and chitin synthesis inhibitors. In addition, compounds that selectively interact with the insect nicotinic acetylcholine receptor, such as imidacloprid, acetamiprid and thiamethoxam, have been introduced for the control of aphids, whiteflies and other insect species. Natural products acting selectively on insect pests, such as avermectins, spinosad and azadirachtin, have been introduced for controlling selected groups of insect pests. Compounds acting on the nervous site that controls the sucking pump of aphids and whiteflies, such as pymetrozine, or respiration, such as diafenthiuron, have been introduced for controlling sucking pests. All the above compounds are important components in pest and resistance management programs.     

Synthesis of some novel dimethine,bis-dimethine cyanine dyes and octacosamethine cyanine dyes endowed with promising biological potency against (HepG2), (Hela), (MCF-7), (MIA), (SN12C) and (H358) cell lines

Successfully, one step two component synthesis of dimethine cyanine dyes, bis-dimethine cyanine dyes and icosamethine cyanine dyes 2–10via reaction of pyridinium salt 1 with some different aldehydes hope to obtain these compounds with enhanced biological potency as antitumor agents against spontaneous liver (HepG2), cervical (Hela), breast (MCF-7), pancreas (MIA), kidney (SN12C) and lung (H358). The impact of substituted drugs on the tumor cells was reflected by means of structure activity relationship (SAR). Among these dyes, icosamethine cyanine dye 8 recorded an excellent activity toward all the tested cell lines. The newly destined drugs were identified and emphasized by spectroscopy and elemental analyses.     

Efficacy and cross-resistance studies on N, N'-bis (3,4 ditrifluoromethylphenyl) methylmalonamide, a novel anticoccidial agent.

N,N'-bis (3,4 ditrifluoromethylphenyl) methylmalonamide (Sch 18545) completely controlled a mild Eimeria necatrix infection at 50, 40 or 30 p.p.m. in the diet, and controlled E. tenella infections at 50 and 40 p.p.m. Slight oocyst passage was observed at each E. tenella treatment level with a marked increase at the 30 p.p.m. treatment level. Fifty p.p.m. were necessary to control E. acervulina infections; levels of 40 p.p.m. reduced E. acervulina oocyst production while 30 p.p.m. were ineffective. Evaluations of Sch 18545 using a mixed infection (Coccivac D) further suggested that activity with this compound was weakest against E. acervulina. Weight gains decreased with increasing concentration of drug in the diet of treated, infected birds and thus the compound showed an insufficient safety margin to be of practical value. Such 18545 administered at 35 p.p.m. in the diet was effective against amprolium, zoalene, aklomide or nicarbazin-resistant strains of E. tenella.     

Graphium agamemnon Linnaeus (Lepidoptera: Papilionidae), a pest of soursop (Annona muricata Linnaeus), in Vietnam: Biology and a novel method of control

Few butterflies are pests of economic significance, but some may be locally destructive, such as the papilionid Graphium agamemnon Linnaeus, which is known to feed on the commercially important soursop (Annona muricata Linnaeus) in Vietnam. This paper documents the life history and ecology of G. agamemnon and investigates commonly used control measures in south‐east Vietnam. A novel method of controlling G. agamemnon infestation is described. If soursop basal rootstock (Annona glabra Linnaeus) is encouraged to shoot during times of peak butterfly activity, ovipositing G. agamemnon females are preferentially attracted to the new growth where the resulting early stages may be easily detected and removed by hand.     

PD 142676 (CI 1002), a novel anticholinesterase and muscarinic antagonist

Inhibition of brain acetylcholinesterase (AChE) can provide relief from the cognitive loss associated with Alzheimer's disease (AD). However, unwanted peripheral side effects often limit the usefulness of the available anticholinesterases. Recently, we identified a dihydroquinazoline compound, PD 142676 (CI 1002) that is a potent anticholinesterase and a functional muscarinic antagonist at higher concentrations. Peripherally, PD 14276, unlike other anticholinesterases, inhibits gastrointestinal motility in rats, an effect consistent with its muscarinic antagonist properties. Centrally, the compound acts as a cholinomimetic. In rats, PD 142676, decreases core body temperature. It also increases neocortical arousal, as measured by quantitative electroencephalography, and cortical acetylcholine levels, measured by in vivo microdialysis. The compound improves the performance of C57/B10j mice in a water maze task and of aged rhesus monkeys in a delayed match-to-sample task involving short-term memory. The combined effect of AChE inhibition and muscarinic antagonism distinguishes PD 142676 from other anticholinesterases and may be useful in treating the cognitive dysfunction of AD and produce fewer peripheral side effects.     

Biorational insecticides: mechanism and cross-resistance

Potency and cross-resistance of various biorational insecticides, exemplified by the whitefly Bemisia tabaci, have been studied. Bemisia tabaci were exposed to the juvenile hormone mimic pyriproxyfen for the past 12 years resulting in an over 2,000-fold resistance, but there was no appreciable cross-resistance with the benzoylphenyl urea novaluron. Similarly, no cross-resistance was found between pyriproxyfen and the two neonicotinoids, acetamiprid and imidacloprid. On the other hand, a slight cross-resistance of 5-13-fold was observed with another neonicotinoid thiamethoxam. Among the neonicotinoids, a resistant strain of B. tabaci to thiamethoxam (approximately 100-fold) showed no appreciable cross-resistance to either acetamiprid or imidacloprid, while another strain 500-fold resistant to thiamethoxam resulted in a mild of 4-6-fold resistance to acetamiprid and imidacloprid. In other assays, B. tabaci strain resistant to thiamethoxam (approximately 100-fold) had no cross-resistance to pyriproxyfen. Our findings indicate that no appreciable cross-resistance was observed between the benzoylphenyl urea novaluron, the juvenile hormone mimic pyriproxyfen, and the neonicotinoids acetamiprid and imidacloprid. Hence, these compounds could be used as components in insecticide resistance management programs.     

Borato-1,2-diaminocyclohexane platinum (II), a novel anti-tumor drug

Borato-1,2-diaminocyclohexane platinum (II) (BDP) was synthesized and compared to cisplatin (cisPt) as a potential anti-tumor drug. BDP and cisPt (0.2-20 microM) dose-dependently inhibited DNA synthesis in L1210 murine leukemia cells, DU-145 prostate cancer cells, A549 lung carcinoma cells, and MCF-7 breast cancer cells, as judged by measuring [(3)H]-thymidine incorporation. BDP and cisPt induced killing of L1210 murine cells by 97 and 78%, respectively. The LD(50) was 35 and 14 mg/kg for BDP and cisPt, respectively. Interestingly, while cisPt (at optimal dose) induced a 100% increase in life span (ILS) of BDF1 mice bearing L1210 tumor cells, BDP (at optimal dose) induced a 200% increase in ILS in the same tumor model. In conclusion, BDP is a novel platinum derivative compound that appears more effective in increasing the ILS than cisplatin against the leukemia tumor mouse model.     

Metalloprobes: synthesis, characterization, and potency of a novel gallium(III) complex in human epidermal carcinoma cells

Multidrug resistance (MDR) mediated by overexpression of the MDR1 gene product, P-glycoprotein (Pgp), represents one of the best characterized barriers to chemotherapeutic treatment in cancer and may be a pivotal factor in progression of Alzheimer's disease (AD). Thus, agents capable of probing Pgp-mediated transport could be beneficial in biomedical imaging. Herein, we synthesized and structurally characterized a gallium(III) complex (5) of the naphthol-Schiff base ligand. The crystal structure revealed octahedral geometry for the metallodrug. Cytotoxicity profiles of 5 were evaluated in KB-3-1 (Pgp-) and KB-8-5 (Pgp+) human epidermal carcinoma cell lines. Compared with an LC(50) (the half-maximal cytotoxic concentration) value of 1.93 microM in drug-sensitive (Pgp-) cells, the gallium(III) complex 5 demonstrated an LC(50) value>100 microM in drug-resistant (Pgp+) cells, thus indicating that 5 was recognized by the Pgp as its substrate, thereby extruded from the cells and sequestered away from their cytotoxic targets. Radiolabeled analogues of 5 could be beneficial in noninvasive imaging of Pgp-mediated transport in vivo.     

Steroidogenic acute regulatory protein (StAR), a novel mitochondrial cholesterol transporter

Cholesterol is a vital component of cellular membranes, and is the substrate for biosynthesis of steroids, oxysterols and bile acids. The mechanisms directing the intracellular trafficking of this nearly insoluble molecule have received increased attention through the discovery of the steroidogenic acute regulatory protein (StAR) and similar proteins containing StAR-related lipid transfer (START) domains. StAR can transfer cholesterol between synthetic liposomes in vitro, an activity which appears to correspond to the trans-cytoplasmic transport of cholesterol to mitochondria. However, trans-cytoplasmic cholesterol transport in vivo appears to involve the recently-described protein StarD4, which is expressed in most cells. Steroidogenic cells must also move large amounts of cholesterol from the outer mitochondrial membrane to the first steroidogenic enzyme, which lies on the matrix side of the inner membrane; this action requires StAR. Congenital lipoid adrenal hyperplasia, a rare and severe disorder of human steroidogenesis, results from mutations in StAR, providing a StAR knockout of nature that has provided key insights into its activity. Cell biology experiments show that StAR moves large amounts of cholesterol from the outer to inner mitochondrial membrane, but acts exclusively on the outer membrane. Biophysical data show that only the carboxyl-terminal alpha-helix of StAR interacts with the outer membrane. Spectroscopic data and molecular dynamics simulations show that StAR's interactions with protonated phospholipid head groups on the outer mitochondrial membrane induce a conformational change (molten globule transition) needed for StAR's activity. StAR appears to act in concert with the peripheral benzodiazepine receptor, but the precise itinerary of a cholesterol molecule entering the mitochondrion remains unclear.     

Synthesis and SAR of novel imidazoquinoxaline-based Lck inhibitors: improvement of cell potency

A series of anilino(imidazoquinoxaline) analogues bearing solubilizing side chains at the 6- and 7-positions of the fused phenyl ring has been prepared and evaluated for inhibition against Lck enzyme and of T-cell proliferation. Significant improvement of the cellular activity was achieved over the initial lead, compound 2.     

Insecticide resistance and cross-resistance in the house fly (Diptera: Muscidae)

A house fly strain, ALHF, was collected from a poultry farm in Alabama after a control failure with permethrin, and further selected in the laboratory with permethrin for five generations. The level of resistance to permethrin in ALHF was increased rapidly from an initial 260-fold to 1,800-fold after selection. Incomplete suppression of permethrin resistance by piperonyl butoxide (PBO) and S,S,S,-tributylphosphorotrithioate (DEF) reveals that P450 monooxygenase- and hydrolase-mediated detoxication, and one or more additional mechanisms are involved in resistance to permethrin. The ALHF strain showed a great ability to develop resistance or cross-resistance to different insecticides within and outside the pyrethroid group including some relatively new insecticides. Resistance to beta-cypermethrin, cypermethrin, deltamethrin, and propoxur (2,400-4,200-, 10,000-, and > 290-fold, respectively, compared with a susceptible strain, aabys) in ALHF house flies was partially or mostly suppressed by PBO and DEF, indicating that P450 monooxygenases and hydrolases are involved in resistance to these insecticides. Partial reduction in resistance with PBO and DEF implies that multiresistance mechanisms are responsible for resistance. Fifteen- and more than fourfold resistance and cross-resistance to chlorpyrifos and imidacloprid, respectively, were not effected by PBO or DEF, indicating that P450 monooxygenases and hydrolases are not involved in resistance to these two insecticides. Forty-nine-fold cross-resistance to fipronil was mostly suppressed by PBO and DEF, revealing that monooxygenases are a major mechanism of cross-resistance to fipronil. Multiresistance mechanisms in the ALHF house fly strain, however, do not confer cross-resistance to spinosad, a novel insecticide derived from the bacterium Saccharopolyspora spinosa. Thus, we propose that spinosad be used as a potential insecticide against house fly pests, especially resistant flies.     

I(ARC), a novel arachidonate-regulated, noncapacitative Ca(2+) entry channel

Along with the inositol trisphosphate-induced release of stored Ca(2+), a receptor-enhanced entry of Ca(2+) is a critical component of intracellular Ca(2+) signals generated by agonists acting at receptors coupled to the activation of phospholipase C. Although the simple emptying of the intracellular Ca(2+) stores is known to be capable of activating Ca(2+) entry via the so-called "capacitative" mechanism, recent evidence suggests that Ca(2+) entry at physiological agonist concentrations, where oscillatory Ca(2+) signals are typically observed, does not conform to such a model. Instead, a noncapacitative Ca(2+) entry pathway regulated by arachidonic acid appears to be responsible for Ca(2+) entry under these conditions. Using whole-cell patch clamp techniques we demonstrate that low concentrations of arachidonic acid activate a Ca(2+)-selective current that is superficially similar to the store-operated current I(CRAC), but which also demonstrates certain distinct features. We have named this novel current I(ARC) (for arachidonate-regulated calcium current). Importantly, I(ARC) can be readily activated in cells whose Ca(2+) stores have been maximally depleted. I(ARC) represents a novel Ca(2+) entry pathway that is entirely separate from those activated by store depletion and is specifically activated at physiological levels of stimulation.     

Isolation and biochemical characterization of a novel leguminous defense peptide with antifungal and antiproliferative potency

Leguminous plants have formed a popular subject of research owing to the abundance of proteins and peptides with important biological activities that they produce. The antifungal proteins and peptides have been purified from a number of leguminous species. However, research continues to discover novel antifungal plant-produced peptides and proteins are being needed, specially those novel ones with both antifungal activity and other significant bioactivities. The objective of this study was to isolate a novel peptide from Phaseolus limensis. A 6.8 kDa peptide designated Limyin, with both antifungal and antiproliferative activity, was isolated from the large lima bean (P. limensis) legumes. The isolation procedure consisted of extraction, precipitation, affinity chromatography on Affi-gel blue gel, ion chromatography on SP-Toyopearl, and gel filtration on Superdex 75. Its N-terminal sequence was determined to be KTCENLATYYRGPCF, showing high homology to defensin and defensin precursors from plants. It potently suppressed mycelial growth in Alternaria alternata, Fusarium solani, and Botrytis cinerea. Its antifungal activity was stable up to 80°C. It showed antiproliferative activity towards tumor cells including human liver hepatoma cells Bel-7402 and neuroblastoma cells SHSY5Y. However, it had no effect on bacteria Staphylococcus aureus and Salmonella. The present findings make a significant addition of the research on leguminous plants.