Leishmaniasis is endemic in tropical regions, and currently affects 12 million people in 88 countries. This disease is transmitted by small biting sandflies (Phlebotomus sp.). The first-line drugs for the treatment of leishmaniasis are pentavalent antimonials such as N-methylglucamine antimonate (Glucantime) and sodium stilbogluconate (Pentostam). However, these drugs are toxic and generally expensive. From these reasons, we have been searching for newe treatment from medicinal plant resources. Three new sesquiterpenoid lactones were isolated from Peruvian folk medicine, Elephantopus mollis (local name: Lingua de vaca) together with four known sesquiterpenoids. They exhibited potent in vitro leishmanicidal activities against Leishmania major. The α-methylene-γ-butyrolactone moiety was found to be essential to the potent leishmanicidal effect observed. Leishmanicidal activities of benzophenanthridine alkaloids isolated from fruits of Bocconia pearcei and their derivatives were examined. Seven benzophenanthridine compounds were isolated from the methanolic extracts of B. pearcei. Among them, chelerythrine showed the most potent leishmanicidal activity (IC_<50> value: <0.001μg/ml). To examine the structure-activity relationship of the benzophenanthridine skeleton, the leishmanicidal activities for 32 synthetic samples were examined. The existence of bulky groups at the C_7-C_8 position was found to enhance the activity. On the other hand, bulkiness at the C_2-C_3 position on the D-ring, a carbonyl group at C-6, substitution at C-6 and cleavage or saturation of the C_5-C_6 bond reduced activity. A methyl group on nitrogen of the C-ring was thought to be necessary for significant activity. A new furostan-type saponin was isolated from the methanolic extract of Brunfelsia grandiflora (local name: Chilicsanango) leaves, together with four known compounds. The chemical structure of an active sonstituent was determined by spectroscopic analysis and chemical reaction to be 26-O-β-D-glucopyranosyl 22ξ-methoxyfurost-3β,26-diol3-O-β-D-xylopyranosyl(1→3)- {β-D-glucopyranosyl(1→2)}-β-D-glucopyranosyl(1→4)- β-D-glucopyranoside. Two new compounds, millettilone A and millettilone B, were isolated from the methanol extract of Millettia pendula (local name: Thinwin), together with six known compounds. Among these, pendulone showed the most potent leishmanicidal activity. Millettilone B, was found to be a purple pigment in this heartwood. Clinical trial tests of Japanese Kampo Medicine Ointment "Shi-un-kou" against cutaneous leishmaniasis were examined in Peru. 53 patients with Leishmaniasis cutaneous, voluntary and with consent, were applied "Shin-un-kou" getting as result 46 patients had heal lesions, 3 no answer, 1 left treatment and 3 abandon treatment.
