title: In silico stereo-electronic analysis of PMD (p-Menthane-3-8-Diol) and its derivatives for pharmacophore development may aid discovery of novel insect repellents.
abstract: PMD (p-menthane-3-8-diol) is an insect repellent that can be synthesized chemically or derived from a steam distillate residue of the leaves of lemon eucalyptus, Corymbia citriodora. It is one of the few natural product endorsed by the Center for Disease Control (USA) for topical application to protect against mosquitoes though it is not as effective as the common repellent DEET (N,N -diethyl-1,3-toluamide). However, DEET has several undesirable side effects and toxicity too. Thus, although PMDs are comparatively safer than DEET, no quantitative structure activity relationship (QSAR) and pharmacophore modeling studies have been reported in literature to improve efficacy and aid further development of more effective PMD analogues. In this study, we report results of quantum chemical analysis of stereoelectronic properties and pharmacophore modeling of PMD and eight of its synthetic derivatives to aid discovery and design of more effective PMD analogues. Stereo-electronic analysis indicates that lower aqueous stabilization (favorable lipophilicity) and larger separation of electrostatic potential energy together with a large localized negative electrostatic potential region by the oxygen atom play important roles for repellent activity. Consistent to these properties, the generated pharmacophore model of the PMDs showed two aliphatic hydrophobic and a hydrogen-bond donor features for potent activity. These results aided us to design more effective PMD repellents which are currently under further investigations.
authors.affiliation: Department of Regulated Laboratories, Division of Regulated Activities, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. apurba1995@yahoo.com
authors.forename: Apurba K
authors.initials: AK
authors.lastname: Bhattacharjee
mesh_terms: D003198:Computer Simulation; D017076:Computer-Aided Design; D000081005:Cyclohexane Monoterpenes; D007302:Insect Repellents / Q000737:chemistry*; D008610:Menthol / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D027822:Myrtaceae / Q000737:chemistry; D055672:Static Electricity
chemical_list: D000081005:Cyclohexane Monoterpenes; D007302:Insect Repellents; D008610:Menthol; C005804:terpin