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Papyracillic acid and its derivatives as biting deterrents against Aedes aegypti (Diptera: Culicidae): structure–activity relationships

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Abstract

Aedes aegypti L. is the major vector of the arboviruses responsible for dengue fever, one of the most devastating human diseases. Papyracillic acid, the main phytotoxin produced by Ascochyta agropyrina var. nana, was evaluated in a preliminary screening together with other fungal phytotoxins, cyclopaldic acid, seiridin and sphaeropsidin A for their biting deterrent and larvicidal activities against Ae. aegypti. Because papyracillic acid previously showed a strong mosquito biting deterrent activity, five already known and six new derivatives were prepared in the current study to carry out a structure–activity relationship. All the compounds showed biting deterrence higher than the solvent control, ethanol. Biting deterrent activity of compounds 8, 9, 10 and 12 with biting deterrent index values of 0.76, 0.86, 0.72 and 0.74 nmol/cm2 was similar to DEET, which was 25 nmol/cm2. None of these compounds showed any larvicidal activity at the highest testing dose of 100 ppm. The bioassay results indicated that the structural feature responsible for the activity of compound 1 was probably the furanone ring. The presence of the alternative substituted cyclobutene, oxiran or substituted 4H-1,2,3-oxadiazine rings in some derivatives may be responsible for an increase in activity.

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Acknowledgments

The manuscript was supported in part by a Grant from the Italian Ministry of University and Research (MIUR), in part by USDA/ARS Grant No. 56-6402-1-612 and Deployed War-Fighter Protection Research Program Grant funded by the US Department of Defense through the Armed Forces Pest Management Board. The authors thank the Istituto di Chimica Biomolecolare del CNR, Pozzuoli, Italy, for recording NMR spectra. We thank Dr. James J. Becnel, Mosquito and Fly Research Unit, Center for Medical, Agricultural and Veterinary Entomology, USDA-ARS, Gainesville, Florida, USA, for supplying Ae. aegypti eggs. The authors wish to thank Dr. Jon F. Parcher, National Center for Natural Products Research, The University of Mississippi, University, MS 38677 USA, for English grammar corrections and suggestions.

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Author notes

  1. Nurhayat Tabanca

    Present address: Department of Entomology and Nematology, Emerging Pathogens Institute, University of Florida, Gainesville, FL, 32610, USA

Authors and Affiliations

  1. Dipartimento di Science Chimiche, Università di Napoli Federico II, Complesso Universitario Monte Sant’Angelo, Via Cintia 4, 80126, Naples, Italy

    Alessio Cimmino, Marco Evidente, Marco Masi & Antonio Evidente

  2. National Center for Natural Products Research, The University of Mississippi, University, MS, 38677, USA

    Abbas Ali, Nurhayat Tabanca & Ikhlas A. Khan

  3. Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, MS, 38677, USA

    Ikhlas A. Khan

Authors
  1. Alessio Cimmino
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Correspondence to Nurhayat Tabanca or Antonio Evidente.

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Cimmino, A., Evidente, M., Masi, M. et al. Papyracillic acid and its derivatives as biting deterrents against Aedes aegypti (Diptera: Culicidae): structure–activity relationships. Med Chem Res 24, 3981–3989 (2015). https://doi.org/10.1007/s00044-015-1439-0

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