Hot Topics in Medicinal Chemistry (Track)


Mercy Githua

Department of Chemistry, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya


Seven Meliaceae plants namely: Turraea abyssinica Hochst., Trichilia dregeana Harv. & Sond, Trichilia emetica Vahl., Toona ciliata M. Roem., Azadirachta indica A. Juss., Turraea mombassana Hiern ex C.DC., Melia azedarach L. were investigated for in vitro antitrypanosomal activity. Methanol extracts of different parts of the plants (stem barks, stem, roots and leaves) were obtained and evaluated for their in vitro antitrypanosomal activities against Trypanosoma brucei rhodesiense. The active extracts were partitioned between water and chloroform and each fraction screened for in vitro antitrypanosomal activities. Bioassay guided chromatographic separations were done and structure elucidation performed. Methanol extract of Toona ciliata roots exhibited the highest antitrypanosomal activity with MIC = 6.95 µg/ml followed by Azadirachta indica leaves and roots with MIC = 51.2 and 145.8 µg/ml, respectively. Antitrypanosomal activities of their chloroform extracts were even higher with T. ciliata having an MIC  = 3.2 µg/ml while A. indica leaves and roots had MIC = 4.4 and 8.5 µg/ml, respectively. Chromatograhpic separations of chloroform fractions yielded several fractions, with limonoid rich fractions showing marked antitrypanosomal activities. Normal and reverse phase column chromatography of the limonoid rich fractions of A. indica leaves followed by preparative HPLC yielded nine pure compounds which were screened for antitrypanosomal activity individually and in blends. Five of the compounds were characterized using NMR (1H, 13C, gradient COSY, gradient HMQC and HMBC), MS, FTIR and UV data. They were all found to have the nimbolide and nimbin basic structures. This study shows that Meliaceae plants are potential sources of trypanocidal drugs and since they are readily available they could be exploited for development of new efficient medicines that are more appropriate and affordable than the few existing drugs.

Phytochemical screening of the methanol extracts of each plant were performed by standard procedures. Methanol extracts of A. nilotica (stem bark), B. buonopozense (stem bark), T. avicennioides (round fruit) and Z. zanthoxyloides (stem bark) were effective on trypanosomes. The extracts of A. nilotica and B. buonopozense exhibited antitrypanosomal effects at 200 and 300 mg/kg body weight respectively. Doses were able to clear the parasites from circulation within 6 and 7 days of treatment respectively with prolonging survival period of up to 30 days. While the extracts of T. avicennioides and Z. zanthoxyloides showed trypanostatic effects and could not clear the parasites completely. The methanol extracts of these plants contain metabolites that are associated with antitrypanosomal effects; therefore, these medicinal plants may be sources of new compounds that may be active against T. b. brucei. This study has also justified the claim that some medicinal plants of Nupeland possess antitrypanosomal activity and could be useful in the management of trypanosomiasis