Analysis of molecular stereoelectronic similarity between N,N-diethyl-m-toluamide (DEET) analogs and insect juvenile hormone to develop a model pharmacophore for insect repellent activity.

Full Abstract

Similarity analysis on molecular stereoelectronic properties of N,N-diethyl-m-toluamide (DEET), natural insect juvenile hormone (JH), a synthetic insect juvenile hormone mimic (JH-mimic, undecen-2-yl carbamate), and DEET compounds reveals remarkable similarities that lead to a reliable pharmacophore for the design of efficacious insect repellents and provide insights for understanding the mechanism of repellent action. The study involves an AM1 quantum chemical computational procedure enabling a conformational search for the lowest and most abundant energy conformers of JH, JH-mimic, and 15 DEET compounds and complete geometry optimization of the conformers. Similarity analyses of stereoelectronic properties such as structural parameters, atomic charges, dipole moments, molecular electrostatic potentials, and highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies were performed on JH, JH-mimic, and the DEET compounds. Similarity of stereoelectronic attributes of the amide/ester moiety, negative electrostatic potential regions beyond the molecular surface, and a large distribution of hydrophobic regions in the compounds appears to be the 3 important factors leading to a similar interaction with the JH receptor. The similarity of electrostatic profiles beyond the molecular surface is likely to play a crucial role toward molecular recognition interaction with the JH receptor from a distance which suggests a possible electrostatic bioisosterism of the amide group of the DEET compounds and JH-mimic and, thus, a model for molecular recognition at the JH receptor.

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Author information

Author/s: Bhattacharjee, Apurba K (AK); Gupta, Raj K (RK);

Affiliation: Department of Medicinal Chemistry, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.

Journal and publication information

Publication Type: Journal Article

Journal: Journal of the American Mosquito Control Association (J Am Mosq Control Assoc), published in United States. (Language: eng)

Reference: 2005-Dec; vol 21 (issue 4 Suppl) : pp 23-9

Dates: Created 2006/08/22; Completed 2006/09/06; Revised 2008/11/21;

PMID: 16921680, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Aedes
Animals
DEET - analogs & derivatives; chemistry
Humans
Insect Repellents - chemistry

Associated Chemicals: Insect Repellents (0) ; Juvenile Hormones (0) ; DEET (134-62-3)

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