Chemical modification of the biologically active compound, thymol

Abstract

The study was earned to chemically modify a biologically active compound thymol, on the hydroxyl (-OH) functional group into its ester, ether and triazole derivatives. A generalised esterification and etherification reactions were employed to introduce an ester and ether functional groups respectively, and the azide-alkyne click reaction was employed to introduce the triazole moiety. Sixteen ester and nine ether derivatives of thymol were synthesised of which eight esters and five ethers are been reported for the first time. Ten novel 1, 2, 3-triazole derivatives of thymol were successfully synthesised. Two novel thymol-parthenin coupled products were successfully synthesised. All the prepared compounds were in excellent yields and of high purity. The compounds were characterised by one or more of the following spectral data; ’H-NMR, 13C-NMR, LC-QTOF/MS, GC-MS-E1/CI and IR. The larvicidal and adulticidal assay of the ester and ether derivatives against the Anopheles gambiae s.s revealed they possess moderate to excellent drug-like characteristics. The most potent larvicidal derivative, 2-Isopropyl-5- methylphenoxy-3-chloro methyl benzene (TM 20) recorded an LC50 value of 1.90 mg/L after 12 hours of exposure time, about 8 folds higher in potency compared to the parent compound, thymol with an LC50 value of 15.01 mg/L after 72 hours of exposure time. The most potent adulticidal derivative is 2- lsopropyl-5-methylphenyl-2-methylpropanoate (TM 1C) with an LC50 value of 16.02 mg/L compared to thymol with an LC50 value of 27.60 mg/L after seven days of exposure time. These derivatives could serve as useful candidate insecticides against the larvae and adult female Anopheles gambiae s.s since they showed the highest bioactivity.