Synthesis and biological evaluation of 3,5-dimethoxystilbene analogs

Authors: WENG, JIAN-QUAN - ZHEJIANG NORMAL UNIVERSITY; ALI, ABBAS - UNIVERSITY OF MISSISSIPPI; ESTEP, ALDEN - COLLABORATOR; Becnel, James; MEYER, SUSAN; WEDGE, DAVID; JACOB, MELISSA - UNIVERSITY OF MISSISSIPPI; RIMANDO, AGNES

Submitted to: Chemistry and Biodiversity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/15/2016
Publication Date: 7/23/2016
Publication URL: http://handle.nal.usda.gov/10113/63184
Citation: Weng, J., Ali, A., Estep, A., Becnel, J.J., Meyer, S.L., Wedge, D.E., Jacob, M., Rimando, A.M. 2016. Synthesis and biological evaluation of 3,5-dimethoxystilbene analogs. Chemistry and Biodiversity. 13(9):1165-1177.

Interpretive Summary: In our on-going studies to discover natural product-based pest management agents, we synthesized analogs of a stilbene compound that has been previously reported as potent against the mosquito (Aedes aegypti) vector for the transmission of dengue. Of the 33 analogs synthesized two compounds (designated as compounds 11 and 12) showed strong inhibition of mosquito larvae. Additional tests showed compounds 11 and 12 exhibited were highly effective against larvae of pesticide-susceptible and pyrethroid-resistant strains of Ae. aegypti but their activity against the adult mosquitoes was low. The 33 synthetic derivatives were also tested for inhibition of some agriculturally important fungi; three demonstrated strong inhibition of Colletotrichum species, which cause economically significant diseases of cereals, grasses, legumes, vegetables, fruits and ornamental plants worldwide. Activity of the synthetic derivatives against some human pathogens was also explored; three showed moderate activity against the microorganisms tested. No single derivative demonstrated activity in all the tests, indicating specific activities. Of interest are compounds 11 and 12, which were active against mosquito larvae and some human pathogens.

Technical Abstract: In our continuing effort to discover natural product-based pest management agents, derivatives of 3,5-dimethoxystilbene were synthesized yielding 27 new and 6 known compounds. Of these, compounds 11 and 12 showed strong Aedes aegypti larvicidal activity (LC50 14.7 and 16.2 ppm, respectively). In further tests, 11 and 12 exhibited high effectiveness against larvae of pesticide-susceptible and pyrethroid-resistant strains of Ae. aegypti; activity against the adult mosquitoes was low. When tested for activity against the root-knot nematode (Meloidogyne incognita), compounds 6f, 6g, and 6i at either 83.3 or 166.7 µg/ml reduced the mobility of second-stage juveniles (J2) that hatched from eggs immersed in the test compounds for 7 days. However, there was little or no effect on J2 placed directly into these compounds, and none of the analogs suppressed M. incognita egg hatch. The compounds were tested for inhibition of some agriculturally important fungi; 6a, 7a and 7e demonstrated strong inhibition of Colletotrichum species. Activity of the stilbenes against some human pathogens was also explored; 11, 12, and 16 showed moderate inhibitory activity against Cryptococcus neoformans, Staphylococcus aureus, methicillin-resistant S. aureus and Mycobacterium intracellulare. Except for 11 and 12, which were active against mosquito larvae and some human pathogens, no single analog demonstrated activity in all the tests, indicating specific activities. Synthesis of the analogs and structure-activity relationships are discussed.