bisabolol and nerolidol

Anopheles gambiae, An. coluzzii, An. arabiensis, and An. funestus are major vectors in high malaria endemic African regions. Various terpenoid classes form the main chemical constituent repository of essential oils, many of which have been shown to possess insecticidal effects against Anopheles species. The current study aimed to assess the bioactivity of terpenoids including four sesquiterpene alcohols, farnesol, (-)-α-bisabolol, cis-nerolidol, and trans-nerolidol; a phenylpropanoid, methyleugenol, and a monoterpene, (R)-(+)-limonene, using the larvicidal screening assay against the four Anopheles species. The mechanism of action was investigated through in vitro acetylcholinesterase inhibition assay and in silico molecular modelling. All six terpenoids showed potent larvicidal activity against the four Anopheles species. Insights into the mechanism of action revealed that the six terpenoids are strong AChE inhibitors against An. funestus and An. arabiensis, while there was a moderate inhibitory activity against An. gambiae AChE, but very weak activity against An. coluzzii. Interestingly, in the in silico study, farnesol established a favourable hydrogen bonding interaction with a conserved amino acid residue, Cys

Topics: Acetylcholinesterase; Animals; Anopheles; Cholinesterase Inhibitors; Farnesol; Insecticides; Mosquito Vectors; Terpenes

Malaria vector control relies on the use of insecticides for indoor residual spraying and long-lasting bed nets. However, insecticide resistance to pyrethroids among others, has escalated. Anopheles funestus, one of the major African malaria vectors, has attained significant levels of resistance to pyrethroids. Overexpressed P450 monooxygenases have been previously identified in pyrethroid resistant An. funestus. The escalating resistance against conventional insecticides signals an urgent need for identification of novel insecticides. Essential oils have gained recognition as promising sources of alternative natural insecticides. This study investigated six essential oil constituents, farnesol, (-)-α-bisabolol, cis-nerolidol, trans-nerolidol, methyleugenol, santalol (α and β isomers) and essential oil of sandalwood, for the adulticidal effects against pyrethroid-resistant An. funestus strain. The susceptibility against these terpenoids were evaluated on both pyrethroid-susceptible and resistant An. funestus. Furthermore, the presence of overexpressed monooxygenases in resistant An. funestus was confirmed. Results showed that both the pyrethroid-susceptible and resistant An. funestus were susceptible to three EOCs; cis-nerolidol, trans-nerolidol and methyleugenol. On the other hand, the pyrethroid-resistant An. funestus survived exposure to both farnesol and (-)-α-bisabolol. This study however does not show any direct association of the overexpressed Anopheles monooxygenases and the efficacy of farnesol and (-)-α-bisabolol. The enhanced activity of these terpenoids against resistant An. funestus that has been pre-exposed to a synergist, piperonyl butoxide, suggests their potential effectiveness in combination with monooxygenase inhibitors. This study proposes that cis-nerolidol, trans-nerolidol and methyleugenol are potential agents for further investigation as novel bioinsecticides against pyrethroid-resistant An. funestus strain.

Topics: Animals; Anopheles; Farnesol; Insecticides; Malaria; Mixed Function Oxygenases; Mosquito Control; Mosquito Vectors; Oils, Volatile; Pyrethrins

Malaria is transmitted by infected female Anopheles mosquitoes, and An. arabiensis is a main malaria vector in arid African countries. Like other anophelines, its life cycle comprises of three aquatic stages; egg, larva, and pupa, followed by a free flying adult stage. Current vector control interventions using synthetic insecticides target these stages using adulticides or less commonly, larvicides. With escalating insecticide resistance against almost all conventional insecticides, identification of agents that simultaneously act at multiple stages of Anopheles life cycle presents a cost-effective opportunity. A further cost-effective approach would be the discovery of such insecticides from natural origin. Interestingly, essential oils present as potential sources of cost-effective and eco-friendly bioinsecticides. This study aimed to identify essential oil constituents (EOCs) with potential toxic effects against multiple stages of An. arabiensis life cycle. Five EOCs were assessed for inhibition of Anopheles egg hatching and ability to kill larvae, pupae and adult mosquitoes of An. arabiensis species. One of these EOCs, namely methyleugenol, exhibited potent Anopheles egg hatchability inhibition with an IC

Topics: Animals; Anopheles; Farnesol; Female; Insecticides; Larva; Life Cycle Stages; Malaria; Mosquito Vectors; Oils, Volatile; Propoxur

Topics: Alkyl and Aryl Transferases; Chromatography, High Pressure Liquid; Farnesol; Humans; Hydroxylation; Mass Spectrometry; Molecular Conformation; Monocyclic Sesquiterpenes; NADPH-Ferrihemoprotein Reductase; Saccharomyces cerevisiae; Sesquiterpenes; Stereoisomerism

Sesquiterpenic compounds are natural chemicals present in organisms from different Phylae or Divisions, which have proved to be important bioactive products, namely in potentiating the action of antibiotics. In the first step, the mutagenicity of nine sesquiterpenic compounds (hydrocarbons and alcohols) was screened in a Salmonella typhimurium his(-)-reversion test with strains TA98 and TA100, in the presence or absence of in vitro metabolic activation. Under the test conditions, none of the compounds showed mutagenicity up to a concentration of 222μg/plate. trans-Farnesol, nerolidol, and α-bisabolol displayed cytotoxicity when tested at concentrations ranging from 14 to 222μg/plate. Then, the combined effect of antibiotic-sesquiterpenic compounds was evaluated on two clinically relevant pathogens, Escherichia coli and Staphylococcus aureus, with well-defined resistance-sensitive profiles. The agar-disc diffusion assay revealed that all the combinations of antibiotic-sesquiterpenic compounds increased the antibacterial activity of the antibiotics tested against S. aureus. For E. coli, an antagonistic effect was observed for various combinations on the growth of this bacterium.

Topics: Anti-Bacterial Agents; Biotransformation; Escherichia coli; Farnesol; Monocyclic Sesquiterpenes; Mutagenicity Tests; Mutagens; Salmonella typhimurium; Sesquiterpenes; Staphylococcus aureus

The sesquiterpenoids nerolidol, farnesol, bisabolol, and apritone were investigated for their abilities to enhance bacterial permeability and susceptibility to exogenous antimicrobial compounds. Initially, it was observed by flow cytometry that these sesquiterpenoids promoted the intracellular accumulation of the membrane-impermeant nucleic acid stain ethidium bromide by live cells of Lactobacillus fermentum, suggesting that enhanced permeability resulted from disruption of the cytoplasmic membrane. The ability of these sesquiterpenoids to increase bacterial susceptibility to a number of clinically important antibiotics was then investigated. In disk diffusion assays, treatment with low concentrations (0.5 to 2 mM) of nerolidol, bisabolol, or apritone enhanced the susceptibility of Staphylococcus aureus to ciprofloxacin, clindamycin, erythromycin, gentamicin, tetracycline, and vancomycin. Nerolidol and farnesol also sensitized Escherichia coli to polymyxin B. Our results indicate the practical utility of sensitizing bacteria to antimicrobials with sesquiterpenoids that have traditionally been used as flavorants and aroma compounds in the food and perfume industries.

Topics: Anti-Bacterial Agents; Drug Synergism; Escherichia coli; Farnesol; Lactobacillus; Microbial Sensitivity Tests; Monocyclic Sesquiterpenes; Polymyxin B; Sesquiterpenes; Staphylococcus aureus