Anti-Larval and Growth Disrupting Constituents from Melia Volkensii (Gurke) on Anopheles Gambiae S. S.

Abstract

Malaria is a major global health problem. The disease is transmitted through the bite of anopheline mosquitoes infected with Plasmodium parasites. Control measures have focused on the parasite and the vector. Hopes for eradication of malaria have diminished due to the emergence of drug-resistant strain of the parasites and insecticide resistant vectors. Given the prevalent situation of malaria in Africa, the search for alternative control measures for the parasite and vector is of significant importance. Recent research has focused on traditional plant remedies for malaria, with few studies on the vector. In West and East Africa, plants of the Meliaceae family are widely used as traditional anti-malarials. Meliaceae plants contain compounds that exhibit anti-insect, anti-protozoa, anti-bacterial and anti-filngal activities. Although the anti-insect activity of Melia volkensii is known, the active compound(s) or blend(s) are unknown. Dry, powdered ripe fruits from Melia volkensii were extracted sequentially using hexane, chloroform, ethyl acetate and methanol. The crude extracts were assayed for their anti- larval activities against 3“!-instar Anopheles gambiae s.s larvae. The methanol extract was the most active (LD50 36.3 ppm, after 24 h). Column and high performance liquid chromatography of the n-hexane and ethyl acetate fractions, respectively yielded nine pure compounds; seven known, salannin (51), volkensin (54), epi-volkensin (76), l-cinnamoyltrichilinin (56).melianin B (64) stigmasterol (72) and ohchinin-3-acetate (52); and two new ones: methyl 2-acetyl-2,3- dimethyl-3- { [4’ ’-(6’ ’ ’-oxotetrahydro-2H-pyran-2’ ’ ’-yl)-2 ’ ’ -E-butenyloxy] methylene} octanoate (73) and 1-benzoyltrichilinin (74). While two of these compounds 72 and 73, were isolated from the hexane extract fraction, the rest were isolated from the ethyl acetate extract fractions. Only Pure methyl 2-acetyl-2,3 -dimethyl-3- { [4’ ’-(6’ ’ ’-oxotetrahydro-2H-pyran-2 ’ ’ ’-yl)-2’ ’-E- butenyloxy]methylene}octanoate (73) was isolated in adequate amount for bioassay. This compound was bio-assayed against 3'“-instar An. gambiae s.s larvae and found to be a potent larvicide( LD5@ 68.5 ppm, after 24 h). Although the other compounds were not isolated in adequate amounts for bioassay, their activity could be inferred from the activity of the fractions from which they were isolated. The study showed that the anti-larval compounds from M volkensii were toxic at high doses and possessed growth regulation properties such as delayed pupation and larval-pupal intermediates at lower doses against An. gambiae.