title: Synthesis of phenanthroindolizidine alkaloids and evaluation of their antitumor activities and toxicities.
abstract: We previously reported that phenanthroindolizidine alkaloid 3 and its derivatives had markedly potent in vitro cytotoxicity. However, they had low in vivo antitumor activities and high in vivo toxicities, which was a serious problem. To address this problem, new phenanthroindolizidine derivatives were synthesized and their antitumor activities and toxicities were evaluated. This study describes the relationship between the chemical structures, antitumor activities, and toxicities of these phenanthroindolizidine derivatives. Based on its properties, compound 8 was found to be the most suitable potential antitumor agent.
authors.affiliation: Yakult Central Institute for Microbiological Research, 1796 Yaho, Kunitachi-shi, Tokyo 186 8650, Japan. takashi-ikeda@yakult.co.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Ikeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Yaegashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsuzaki
authors.forename: Ryuta
authors.initials: R
authors.lastname: Yamazaki
authors.forename: Syusuke
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Seigo
authors.initials: S
authors.lastname: Sawada
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D006878:Hydroxides / Q000737:chemistry / Q000378:metabolism; D007212:Indolizines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010618:Phenanthrolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D006878:Hydroxides; D007212:Indolizines; D010618:Phenanthrolines; C031356:hydroxide ion