YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Synthesis of Lipophilic Benz[cd]indole Antifolates and Their Antitumor Activity In Vitro

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

  • Baek Du-Jong (Department of Chemistry, College of Natural Sciences, Sangmyung University)
  • 백두종 (상명대학교 자연과학대학 화학과)
  • Published : 2005.02.01
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Abstract

Nonclassical aminobenz[cd]indole antifolates 4, 5 and 6, in which the glutamic acid moiety of the classical antifolates 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 $IC_{50}$ values. Most effective was compound 4 ($N^6-methyl-N^6$-[4-[(${\alpha}$(S)-aminocarbonylbenzyl) aminocarbonyl]benzyl]-2,6-diaminobenz[cd]indole)with $IC_{50}$ of 2 nM against SW480, human colon adenocarcinoma cell line, which is 650-fold more potent than the reference compound 3.

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References

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