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N-substituted methyl maleamates as larvicidal compounds against Aedes aegypti (Diptera: Culicidae)


Severe human arboviral diseases can be transmitted by the mosquito Aedes aegypti (L.), including dengue, chikungunya, zika, and yellow fever. The use of larvicides in containers that can result as potential breeding places and cannot be eliminated is the main alternative in control programs. However, their continuous and widespread use caused an increase in insecticide-resistant populations of this mosquito. The aim of this study was to evaluate the effect of three N-substituted methyl maleamates as larvicides on Ae. aegypti, the N-propyl methyl maleamate (PMM), N-butyl methyl maleamate (BMM), and N-hexyl methyl maleamate (HMM). These compounds could have a different mode of action from those larvicides known so far. We evaluated the larva mortality after 1 and 24 h of exposure and we found that mortality was fast and occurs within the first 60 min. HMM was slightly more effective with LC50 values of 0.7 and 0.3 ppm for 1 and 24 h of exposure and LC95 of 11 and 3 ppm. Our results demonstrate that N-substituted methyl maleamates have insecticidal properties for the control of Ae. aegypti larvae. These compounds could become useful alternatives to traditional larvicides after studying their insecticidal mechanism as well as their toxicity towards non target organisms.

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  1. Ayesa P, Harrington L, Scott J (2006) Evaluation of novel insecticides for control of dengue vector Aedes aegypti (Diptera: Culicidae). J Med Entomol 43(1):55–60

  2. Bisset J, Blanco S, Braga I, Coto H, Masuh H, Moncayo A, Nathan M, Orellano P, Vázquez J, Zerba E (2005) Protocolo para determinar la susceptibilidad o resistencia a insecticidas de mosquitos de la especie Aedes aegypti. (Protocol to evaluate the susceptibility or resistance to insecticides by Aedes aegypti mosquitoes). Documento propuesto por la Red Latinoamericana de Control de Vectores (RELCOV). Fundación Mundo Sano Eds. Buenos Aires, Argentina 13 pp

  3. Braga IA, Lima JBP, Soares SS, Valle D (2004) Aedes aegypti resistance to temephos during 2001 in several municipalities in the states of Rio de Janeiro, Sergipe and Alagoas, Brazil. Mem Inst Oswaldo Cruz 99(2):199–203.

  4. Brogdon WG, McAllister JC (1998) Insecticide resistance and vector control. Emerg Infect Dis 4(4):605–613.

  5. Cornel AJ, Stanich MA, McAbee RD, Mulligan SF III (2002) High level methoprene resistance in the mosquito Ochlerotatus nigromaculis (Ludlow) in Central California. Pest Manag Sci 58(8):791–798.

  6. Dame DA, Wichterman GJ, Hornby JA (1998) Mosquito (Aedes taeniorhynchus) resistance to methoprene in an isolated habitat. J Am Mosq Control Assoc 14(2):200–203

  7. Frazier JL, Heitz JR (1985) Inhibition of olfaction in the moth Heliothis virescens by the sulfhydryl reagent fluorescein mercuric acetate. Chem Senses Flavor 1:271–281

  8. Gonzalez Audino P, Masuh H, de Licastro SA, Vassena C, Picollo MI, Zerba E (1997) Suppression of food intake in Triatoma infestans by N-substituted methyl maleamates. Pestic Sci 49(4):339–343.<339::AID-PS523>3.0.CO;2-R

  9. Gonzalez PV, Gonzalez Audino PA, Masuh HM (2015) Behavioral response of Aedes aegypti (Diptera: Culicidae) larvae to synthetic and natural attractants and repellents. J Med Entomol 52(6):1315–1321.

  10. Gratz NG, Jany WC (1994) What role for insecticides in vector control programs? Am J Trop Med Hyg 50(6):11–20

  11. Licastro SA, Wallace G, Seccacini E, Gonzalez Audino P, Zerba E (1993) Synthesis and bioactivity of new phosphorodithioates derived from N-substituted maleamic esters. Comp Biochem Physiol 104:43–46

  12. Lichtfield JT, Wilcoxon F (1949) A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther 2:99–113

  13. López SN, Castelli MV, de Campos F, Corrêa R, Cechinel Filho V, Yunes RA, Zamora MA, Enriz RD, Ribas JC, Furlán RL, Zacchino SA (2005) In vitro antifungal properties structure-activity relationships and studies on the mode of action of N-phenyl, N-aryl, N-phenylalkyl maleimides and related compounds. Arzneim Forsch 55:123–132

  14. Ma W, Li X, Dennehy TJ, Lei C, Wang M, Degain BA, Nichols RL (2010) Pyriproxyfen resistance of Bemisia tabaci (Homoptera: Aleyrodidae) biotype B: metabolic mechanism. J Econ Entomol 103(1):158–165.

  15. Macoris MLG, Andrighetti MTM, Takaku L, Glasser CM, Garbeloto VC, Bracco JC (2003) Resistance of Aedes aegypti from the state of S. Paulo, Brazil, to organophosphates insecticides. Mem Inst Oswaldo Cruz 98(5):703–708.

  16. Mehta K, Phillips AP, Lui F, Brooks RE (1960) Maleamic and citraconamic acids, methyl esters and imides. J Org Chem 25(6):1012–1015.

  17. Morita H, Shiraishi A (1985) Chemoreception physiology. In: Kerkut GA, Gilbert LJ (eds) Comprehensive insect physiology, biochemistry and pharmacology, vol 6: Nervous system sensory. Pergamon Press, pp 133–170

  18. Nunes JPM, Morais M, Vassileva V, Robinson E, Rajkumar VS, Smith MEB, Pedley BR, Caddick S, Baker JR, Chudasama (2015) Functional native disulfide bridging enables delivery of a potent, stable and targeted antibody–drug conjugate (ADC). Chem Commun 51(53):10624–10627.

  19. Patil CD, Patil SV, Salunke BK, Salunkhe RB (2012) Insecticidal potency of bacterial species Bacillus thuringiensis SV2 and Serratia nematodiphila SV6 against larvae of mosquito species Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus. Parasitol Res 110(5):1841–1847.

  20. Picollo MI, Seccacini E, Vassena C, Zerba E (1993) Feeding and mating deterrency by sulfhdryl reagents in Triatoma infestans. Acta Trop 53:297–307

  21. Pilger D, De Maesschalckm M, Horstick O, San Martin JL (2010) Dengue outbreak response: documented effective interventions and evidence gaps. TropIKA 1. ( [Accessed 12 July 2017]

  22. Ponlawat A, Scott JG, Harrington LC (2005) Insecticide susceptibility of Aedes aegypti and Aedes albopictus across Thailand. J Med Entomol 42(5):821–825.

  23. Seccacini E, Lucia A, Zerba E, Licastro S, Masuh H (2008) Aedes aegypti (L.) resistance to temephos in Argentina. J Am Mosq Control Assoc 24(4):608–609.

  24. Shah RM, Shad SA, Abbas N (2015) Mechanism, stability and fitness cost of resistance to pyriproxyfen in the house fly, Musca domestica L. (Diptera: Muscidae). Pestic Biochem Physiol 119:67–73.

  25. Sortino M, Cechinel Filho V, Corrêa R, Zacchino S (2008) N-Phenyl and N-phenylalkyl-maleimides acting against Candida spp.: time to-kill, stability, interaction with maleamic acids. Bioorg Med Chem 16(1):560–568.

  26. Stenersen J (2004) Chemical pesticides mode of action and toxicology—chapter two: why is a toxicant poisonous? CRC Press, p 16

  27. Tikar SN, Kumar A, Prasad GBKS, Prakash S (2009) Temephos-induced resistance in Aedes aegypti and its cross-resistance studies to certain insecticides from India. Parasitol Res 105(1):57–63.

  28. World Health Organization (WHO) (1999) Bacillus thuringiensis. Environmental health criteria 217. WHO, Geneva, Switzerland [Accessed 12 July 2017]

  29. World Health Organization (WHO) (2008) Pyriproxyfen in drinking-water: use for vector control in drinking-water sources and containers—background document for development of WHO guidelines for drinking-water quality

  30. World Health Organization (WHO) (2014) A global brief on vector-borne diseases. [Accessed 12 July 2017]

  31. Zaim M, Guillet P (2002) Alternative insecticides: an urgent need. Trends Parasitol 18(4):161–163.

  32. Zentz F, Valla A, Le Guillou R, Labia R, Mathotb AG, Sirot D (2002) Synthesis and antimicrobial activities of N-substituted imides. Il. Farmaco 57(5):421–426.

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Correspondence to Laura Harburguer or Héctor Masuh.

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Harburguer, L., Gonzalez, P.V., Gonzalez Audino, P. et al. N-substituted methyl maleamates as larvicidal compounds against Aedes aegypti (Diptera: Culicidae). Parasitol Res 117, 611–615 (2018).

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  • Aedes aegypti
  • Larvae
  • Larvicide
  • Maleamates