지용성 Benz[cd]indole 엽산길항제의 합성 및 In Vitro 항암활성

• 영문명: Synthesis of Lipophilic Benz(cd)indole Antifolates and Their Antitumor Activity In Vitro
• 발행기관: 대한약학회
• 저자명: 백두종(Du-Jong Baek)
• 간행물 정보: 『약학회지』제49권 제1호 (2005년), 60~67쪽, 전체 8쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2005.02.28

영문 초록

Nonclassical aminobenz[cd]indole antifolates 4, 5 and 6, in which the glutamic acid moiety of the classical anti-folates is substituted by 2-phenylglycinamide or 3- aminobenzamide, were synthesized and their in vitro antitumor activity was evaluated. The purpose of this substitution is that the lipophilicity is enhanced due to the aromatic ring of the target compounds for the passive transport through lipid membrane of cells while the hydrogen bonding of the amide is retained in the active site of the enzyme, thymidylate synthase, where the glutamate is originally present. The target compounds were highly cytotoxic against tumor cell lines of murine and human origin with micromolar to nanomolar Icn values. Most effective was compound 4(N-methyl-N-[4-[(α(S)-aminocarbonylbenzyl) aminocarbonyl]benzyl]-2,6- aminobenz[cd]indole) with Ics of 2 Nm against SW480, human colon adenocarcinoma cell line, which is 650-fold more potent than the reference compound 3.

키워드

benz[cd]indole nonclassical antifolates in vitro antitumor activity