Cytotoxic pheophorbide-related compounds from Clerodendrum calamitosum andC-cyrtophyllum

Three pheophorbide-related compounds (1-3) were isolated from the leaves an d stems of Clerodendrum calamitosum. The methyl ester of 3 (6) and the know n (10S)-hydroxypheophytin a 7) also were isolated from leaves of the relate d plant Clerodendrum cyrtophyllum. Compounds 1 and 6 were isolated for the first time as naturally occurring products from a plant source. All structu res were elucidated by detailed spectroscopic analysis. Biological evaluati on showed that 1 and 2 exhibited strong cytotoxicity against human lung car cinoma (A549), ileocecal carcinoma (HCT-8), kidney carcinoma (CAKI-1), brea st adenocarcinoma (MCF-7), malignant melanoma (SK-MEL-2), ovarian carcinoma (IA9), and epidermoid carcinoma of the nasopharynx (KB), and its etoposide - (KB-7d), vincristine- (KB-VCR), and camptothecin-resistant (KB-CPT) subcl ones. Compound 3 was less cytotoxic than 1 and 2. Compounds 4-6, the methyl esters of 1-3, showed strongly increased cytotoxicity compared with the pa rent acids. Interestingly, 6 was the most active derivative among these com pounds. Compound 7 was inactive.