Progress 10/01/08 to 09/30/10
Outputs
Progress Report Objectives (from AD-416) To devise innovative methods for the suppression of insects that transmit diseases to U.S. military deployed abroad. Approach (from AD-416) Identify and test compounds with insecticidal activity that makes them especially beneficial in the rapid control of mosquitoes, flies, and other arthropods responsible for carrying disease agent. Devise innovative means of applying control agents especially suited for use in combat or deployment conditions. Identify and test new classes of topical and area repellents for use by troops. Compounds from Inula helenium, namely sesquiterpene lactones, were targeted in a structure-activity relationship (SAR) study that continued into 2010. Two of these compounds in particular, alantolactone and isoalantolactone were the subject of a SAR study. To date over 30 isomers of either alantolactone or isoalantolactone have been synthesized. This study in its entirety was published earlier this year. Dried male inflorescences of breadfruit have been traditionally used as a mosquito repellent in Hawaii by burning. We found the activity to be due to three fatty acids, undecanoic acid (C11), the most active, followed by capric acid (C10) and then lauric acid (C12). The smoke of burning Jatropha curcas oil is used in India and Africa to repel mosquitoes and other insects. We discovered the constituents responsible for this biological activity. Both free fatty acid and triglyceride constituents were found to be active in deterring Aedes aegypti from biting. Identification and total synthesis of a natural product analog with higher activity and three times longer duration of action than DEET, the most popular mosquito repellent, was completed. An invention disclosure was filed on this compound. A series of analogs belonging to this compound with varying carbon chain lengths of the attached functional group was synthesized. Two series of amides with 100% larvicide activity at 1 ppm were synthesized. A collaborative project on extraction and fractionation of plant material received from the Alaska Plant Material Center for mosquito repellent activity was initiated. Compounds were submitted for mosquito and tick bioassay. Ongoing projects with aromatic and medicinal plants continued in collaboration with CMAVE. Some of samples were evaluated for toxicity to mosquitoes. Work is still in progress with the active oils. Active Hypericum spp. extracts were followed by bioassay- guided fractionation. Three pure compounds will be evaluated for mosquito adulticidal and larvicidal activity. Hedycium and Pelargonium projects were recently completed. Forty Euphorbiaceae extracts were evaluated for both mosquito adulticidal and larvacidal activity, and four of them were found to have potent activity in both assays. Bioassay-guided fractionation of two active extracts has already been performed in an effort to determine the natural compound(s) responsible for this activity. Thirty-two natural product-based synthetic compounds were evaluated. Two of them had activity at 16 ppm with 100% and 80% mortality of mosquito larvae. No repellent activity was observed. Twenty-five new natural product-based synthetic compounds were bioassayed. Twelve stilbene type and two pterocarpenes obtained from peanut seeds were evaluated for mosquito activity. Seven stilbenes showed 100% mortality at 15 ppm in larval assay. Work is still in progress with the active compounds. Some Egyptian plant extracts and pure compounds were submitted to mosquito larvicidal and adultiticidal activity. One compound had good activity against Ae. aegypti and Culex quinquefasciatu. A project with ligustilide analogs was initiated.
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Progress 10/01/08 to 09/30/09
Outputs
Progress Report Objectives (from AD-416) To devise innovative methods for the suppression of insects that transmit diseases to U.S. military deployed abroad. Approach (from AD-416) Identify and test compounds with insecticidal activity that makes them especially beneficial in the rapid control of mosquitoes, flies, and other arthropods responsible for carrying disease agent. Devise innovative means of applying control agents especially suited for use in combat or deployment conditions. Identify and test new classes of topical and area repellents for use by troops. Significant Activities that Support Special Target Populations Callicarpenal and Intermedeol Studies: Due to the high interest by the private sector to develop this compound as a commercial insect repellent, it was necessary to understand how the structure of callicarpenal could be improved upon and/or simplified while still maintaining effectiveness. Not only was mosquito biting deterrency/repellency of analogs explored but also toxicity towards mosquitoes was established which had not been demonstrated previously. In addition, intermedeol structure-activity relationship studies are underway. Functional groups targeted included the C-4 hydroxyl group, the C-7 and C-13 allylic positions, and the C-11 olefin. Modifications included oxidations, reductions, and substitutions as deemed necessary. Additional isomers need to be synthesized and the work is ongoing. Inula Sesquiterpene Lactone Study: Alantolactone and isoalantolactone were the subject of a lengthy Structure-activity relationship (SAR) study. Throughout a three step/phase process, at least 28 compounds have been synthesized and evaluated for larvicidal and adulticidal activities. Lead candidates have been identified and a manuscript is currently being prepared for publication. Breadfruit Study: ARS scientist at Natural Products Utilization Research Unit (NPURU) in collaboration with the University of British Columbia investigated the folk remedy mosquito repelling properties of Artocarpus altilis. A systematic bioassay-guided fractionation of active extract(s) was performed in an effort to determine the natural compound(s) responsible for this repellent action. To date, multiple bioactive fractions have been identified and demonstrated to be as effective as the crude extract itself. Structure determinations are underway. ARS scientists provided Department of Defense (DOD) with 11 pure compounds and extracts from three plants that cannot be revealed for patent reasons. Some of these compounds showed comparable activity to DEET. The most effect compound had the strongest activity and killed 80% 1st instars larvae at 8 ppm in the tested samples. (Z)-Ligustilide and other phthalide type compounds deterred the biting of A. aegypti and An. Stephensi. (Z)-Ligustilide was more effectively than DEET. Several extracts collected from southern America and tested in both larvicidal and adult topical bioassays. One sample killed 100% of the larva of A. aegypti at 2 ppm. CMAVE is currently testing more than 100 our samples for adulticide and mosquito repellent activity. Synthesis of a series of analogs of a novel class of mosquito repellents with longer duration of activity than DEET was accomplished. These compounds were derived from a natural product isolated from a plant collected in the arid region of Southern Texas. A patent application has been filed. Plant extracts were screened for acetylcholinesterase inhibitory activity. Several compounds responsible for the activity were isolated. These compounds will be tested for selective mosquito acetylcholinesterase activity in a lab.
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