Cytotoxic pheophorbide-related compounds from Clerodendrum calamitosum and C. cyrtophyllum.
Three pheophorbide-related compounds (1-3) were isolated from the leaves and stems of Clerodendrum calamitosum. The methyl ester of 3 (6) and the known (10S)-hydroxypheophytin a (7) also were isolated from leaves of the related plant Clerodendrum cyrtophyllum. Compounds 1 and 6 were isolated for the first time as naturally occurring products from a plant source. All structures were elucidated by detailed spectroscopic analysis. Biological evaluation showed that 1 and 2 exhibited strong cytotoxicity against human lung carcinoma (A549), ileocecal carcinoma (HCT-8), kidney carcinoma (CAKI-1), breast adenocarcinoma (MCF-7), malignant melanoma (SK-MEL-2), ovarian carcinoma (1A9), and epidermoid carcinoma of the nasopharynx (KB), and its etoposide- (KB-7d), vincristine- (KB-VCR), and camptothecin-resistant (KB-CPT) subclones. 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 parent acids. Interestingly, 6 was the most active derivative among these compounds. Compound 7 was inactive.
Cheng
H H
HH
Natural Products Laboratory, Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Wang
H K
HK
Ito
J
J
Bastow
K F
KF
Tachibana
Y
Y
Nakanishi
Y
Y
Xu
Z
Z
Luo
T Y
TY
Lee
K H
KH
D000230:Adenocarcinoma / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology / Q000633:toxicity; D001943:Breast Neoplasms / Q000378:metabolism; D002166:Camptothecin / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002734:Chlorophyll / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005047:Etoposide / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006801:Humans; D007078:Ileal Neoplasms / Q000378:metabolism; D007624:KB Cells / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008545:Melanoma / Q000378:metabolism; D015394:Molecular Structure; D010051:Ovarian Neoplasms / Q000378:metabolism; D018515:Plant Leaves / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013624:Taiwan; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014750:Vincristine / Q000378:metabolism / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D002734:Chlorophyll; D014750:Vincristine; D005047:Etoposide; C032623:pheophorbide a; D002166:Camptothecin