Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
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Synthesis of Benzo[c]phenanthridine Derivatives and their in Vitro Antitumor Activities

  • Cho, Won-Jea (College of Pharmacy, Chonnam National University) ;
  • Yoo, Su-Jeong (College of Pharmacy, Chonnam National University) ;
  • Chung, Byung-Ho (College of Pharmacy, Chonnam National University) ;
  • Choi, Bo-Gil (College of Pharmacy, Chonnam National University) ;
  • Cheon, Seung-Hoon (College of Pharmacy, Chonnam National University) ;
  • Whang, Soon-Ho (College of Pharmacy, KyungHee University) ;
  • Kim, Sin-Kyu (College of Pharmacy, KyungHee University) ;
  • Kang, Boo-Hyon (Screening and Toxicology Research Center, Korea Research Institute of Chemical Technology) ;
  • Lee, Chong-Ock (Screening and Toxicology Research Center, Korea Research Institute of Chemical Technology)
  • Published : 1996.08.01
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Abstract

Aiming at the development of anticancer agents by modification of phenolic benzo[c]phenanthridine alkaloid, additional hydroxyl group was put on C10 position of fagaridine (1) by a biomimetic synthetic procedure to afford 10-hydroxyfagaridine (12). All of the synthetic intermediates were also screened in vitro antitumor activities against five different cell lines as well as 12. Among them the representative cytotoxic results are shown as follows; P-quinone (11) $[ED_50;(A549=0.22; {\mu}g/ml)$, $(HCT;15=0.21 {\mu}g/ml)$, fagaridine (1) $(HCT;15=0.41 {\mu}g/ml)$, olefin (6) $(HCT; 15=0.06 {\mu}g/ml)$, acetal (7) $(SKMEL-2=0.07 {\mu}g/ml)$, dihydrofagaridne (10) $(A549=0.38 {\mu}g/ml)$, 10-hydroxyfagaridine (12) $(A 549=0.45{\mu}g/mi)$. From these observation three main remarks can be drawn; (i) the iminium part of benzo[c]phenanthridine is not essential for showing acitvities, (ii) the additional hydroxyl group did not contribute to enhance the cytotoxicity, (iii) the 3-arylisoquinolin-1(2H)-one derivatives were found to display significant in vitro antitumor activity.

Keywords

References

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