Antimalarial Activity of Tropical Meliaceae Extracts and Gedunin Derivatives

Abstract

Extracts of 22 species of Meliaceae were examined for antimalarial activity using in vitro tests with two clones of Plasmodium falciparum, one sensitive to chloroquine (W2) and one chloroquine-resistant (D6). Twelve extracts were found to have activity, including extracts of Cedrela odorata wood and Azadirachta indica leaves, which contained the limonoid gedunin. These extracts were more effective against the W2 clone than the D6 clone, suggesting there is no cross-resistance to chloroquine. Gedunin was extracted in quantity, and nine derivatives prepared for a structure-activity study, which revealed essential functionalities for activity. The study also included four other limonoids derived from related Meliaceae. Only gedunin had better activity than chloroquine against the W2 clone. This active principle could be used to standardize a popular crude drug based on traditional use of A. indica in West Africa.

Novel Antimalarial Compounds Isolated in a Survey of Self-Medicative Behavior of Wild Chimpanzees in Uganda

“…In vitro antimalarial activities have recently been reported for limonoids from other Meliaceae: bark and seeds of Khaya grandifolia (2), bark of Khaya senegalensis (13), leaves of Azadirachta indica (11), and Cedrela odorata wood (3). The most active limonoid, gedunin, isolated from Khaya grandifolia, Cedrela odorata, and Azadirachta indica (3,16), had a better in vitro activity than chloroquine against clones sensitive to chloroquine (15). Its in vitro activity evaluated against a chloroquine-resistant strain of P. falciparum (IC 50 ϭ 0.72 g/ml) was roughly equivalent to that of trichirubine A (12), but its in vivo activity, initially poor (3), might be improved: for example, when combined with chloroquine (2), by synergism with dillapiol, a cytochrome P-450 3A4 inhibitor, or preparation of a more stable compound (16).…”

Plants as Potential Sources of Pesticidal Agents: A Review

“…The content of the identified components can be used to standardize the crude pesticide as gedunin has been proposed for crude neem-based antimalarial drugs [77]. It is only in this way will the abundant plant-based natural resources of the developing countries be readily and cheaply made available for agricultural production without polluting the environment.…”

Photomediated transformation of eremophilanes-I: Photooxidation of 2ß-angeloyloxy-10ß-H-furanoeremophilane

“…[6][7][8][9] Several natural plant extract containing terpenoids are widely used in agriculture and medicine. 10,11 Photochemical study is expected to through light on improving the stability of these compounds into the biological formulations made from the natural plant extracts containing terpenoids. More over the significance of generation and reactions of 1 O 2 with biomolecules in plants and living systems have been recognized .…”