YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Effects of Quinolone Derivatives on Topoisomerase II

퀴놀론 유도체의 Topoisomerase II에 대한 효과

  • Yeon, Seung-Woo (Research Laboratories, Il-Dong Pharm., Co., Ltd.) ;
  • Paek, Nam-Soo (Research Laboratories, Il-Dong Pharm., Co., Ltd.) ;
  • Kim, Tae-Han (Research Laboratories, Il-Dong Pharm., Co., Ltd.) ;
  • Kim, Kee-Won (Research Laboratories, Il-Dong Pharm., Co., Ltd.)
  • 연승우 (일동제약(주) 중앙연구소) ;
  • 백남수 (일동제약(주) 중앙연구소) ;
  • 김태한 (일동제약(주) 중앙연구소) ;
  • 김기원 (일동제약(주) 중앙연구소)
  • Published : 1996.12.01
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Abstract

Quinolone derivatives, SJ5b (ethyl 5,12-dihydro-5-dihydro-5-oxobenzoxazolo[3,2-a]quinoline-6-carboxylate) and SQ7b (3-fluoro-2-(4-methylpiperazin-1-yl)-5.12-dihydro-5-oxobenzoxa zolo[3,2-a]quinoloine carboxylic acid) showed in vitro cytotoxicities against various tumor cell lines. SJ5b and SQ7b completely inhibited the DNA relaxation activities of human placental topoisomerase II at the concentration of 15.63 and 1.95 ${\mu}$g/ml, respectively. However, unlike etoposide which stabilize the topoisomerase II-DNA complex, SQ7b did not cause topoisomerase II-mediated DNA cleavage and SJ5b weakly stabilized the topoisomerase II-DNA cleavable complex. Through both experiments. DNA relaxation assay by the increment of topoisomerase II concentration and DNA unwinding assay, it was shown that SJ5b and SQ7b did not interact with topoisomerase II itself but bound to DNA. Therefore, it was concluded that DNA binding of SJ5b and SQ7b caused the inhibition of topoisomerase II related to DNA relaxation but no or very weak stabilization of topoisomerase II-DNA cleavable complex. In addition, SJ5b and SQ7b prevented whole cell nucleic acid syntheses in HL60 cells.

Keywords

References

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