Isolation of secondary metabolites from Teclea nobilis and Rapanea melanophloeos active against Schistosoma mansoni

Abstract

Helminthic infections have severe consequences on the health of millions of people worldwide and cause serious economic losses. Synthetic drugs have been effective wormicides, however, they are expensive, show side effects and develop resistance. This has generated interest in the use of plant based anti-helmintics, which seem to offer a reliable, cheap and cost effective method. In this research, the anti-helmintic activity of secondary metabolites from Teclea nobilis and Rapanea melanophloeos, which are used ethnomedically as dewormers, against Schistosoma mansoni are reported. The Teclea nobilis essential oil was extracted using hydro-distillation in a modified Clevenger apparatus. The essential oil was analyzed using gas chromatography-mass spectrometry and determined to be majorly constituted of monoterpenes and sesquiterpenes which had concentrations of 42.21 and 33.09%, respectively. The major monoterpenes were β-Ocimene (10.15%) and γ-Terpinene (6.11%) while major sesquiterpenes were β-Cadinene (4.98%) and 1,6-Germacradien-5-ol (4.38%). The essential oil showed lethal effects against Schistosoma mansoni miracidia with LC50 and LC90 values of 196.29 and 367.24 ppm, respectively. The non-volatiles of both Teclea nobilis and Rapanea melanophloeos were also active against Schistosoma mansoni miracidia. Fractionation of Teclea nobilis and Rapanea melanophloeos leaf ethyl acetate extracts over silica gel column chromatography yielded six compounds which were successfully identified through analysis of their 1D and 2D nuclear magnetic resonance spectroscopy and mass spectrometry data as well as comparison with literature data. Out of the six compounds, Teclea nobilis had four furoquinoline alkaloids; Tecleoxine 10, Methylnkolbisine 13, Kokusagine 21 and Nkolbisine 22 while the Rapanea melanophloeos had two benzoic acid derivatives; Myrsinoic acid B 23 and Myrsinoic acid C 24. All these compounds were active against S. mansoni miracidia. Compound 23 which recorded LC50 and LC90 mortality values of 98.06 and 236.51 ppm, respectively was the most potent followed by compound 24 which registered LC50 and LC90 values of 139.89 and 314.23 ppm, respectively. The compounds 10, 13 and 21, which due to their small amounts could not be separated thus tested as a mixture, registered LC50 and LC90 values of 270.18 and 690.93 ppm, respectively and compound 22 which recorded LC50 and LC90 values of 287.97 and 631.73 ppm, respectively was the least potent. These findings show that these compounds can be used as lead compounds in the development of new, biodegradable, environmentally friendly and more potent miracidiacides or anti-helmintics