Journal of the Korean Chemical Society (대한화학회지)

Korean Chemical Society (대한화학회)
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Syntheses and in vitro Antitumor Activities of 8-Azaxanthine and Its Derivatives

8-Azaxanthine과 그 유도체의 합성 및 시험관내 항암 활성

  • Lee, Bong Hun (Department of Chemistry, College of Natural Science, Pusan National University) ;
  • Shin, Jung Hee (Department of Chemistry, College of Natural Science, Pusan National University) ;
  • Jang, Tae Sik (Department of Chemistry, College of Natural Science, Pusan National University) ;
  • Park, Jang Su (Department of Chemistry, College of Natural Science, Pusan National University) ;
  • Kang, Shin Won (Department of Chemistry, College of Natural Science, Pusan National University)
  • 이봉헌 (부산대학교 자연과학대학 화학과) ;
  • 신정희 (부산대학교 자연과학대학 화학과) ;
  • 장태식 (부산대학교 자연과학대학 화학과) ;
  • 박장수 (부산대학교 자연과학대학 화학과) ;
  • 강신원 (부산대학교 자연과학대학 화학과)
  • Published : 19970700
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Abstract

8-Azaxanthine (1), 3-${\beta}$-D-ribofuranosyl-8-azaxanthine (2), 3-${\beta}$-D-ribofuranosyl-8-azaxanthine-5'-monophosphate (3), and 3-${\beta}$-D-ribofuranosyl-8-azaxanthine-5'-(3-pyridinylcarbonyl)monophosphate (4) were synthesized. The in vitro antitumor activities of the synthesized compounds against P388 mouse leukemia, FM3A mammary carcinoma, and U937 human histiocytic lymphoma cells were determined by MTT assay. 2 with unnatural N-3 and C-1' glycoside bond had activity against three tumor cell lines and $IC_{50}$s of these compounds were 0.05, 0.06, and 0.06 ${\mu}mol/mL$ against three tumor cell lines, respectively. But these compounds had no antibacterial activity. $IC_{50}$s against U937 human histiocytic lymphoma cells were verified with the structural modification: $IC_{50}$s of 1, 2, 3, and 4 were 0.33, 0.06, 0.25, and 0.33 ${\mu}mol/mL$, respectively.

8-Azaxanthine(1), 3-${\beta}$-D-ribofuranosyl-8-azaxanthine(2), 3-${\beta}$-D-ribofuranosyl-8-azaxanthine-5'-monophosphate(3) 그리고 3-${\beta}$-D-ribofuranosyl-8-azaxanthine-5'-(3-pyridinylcarbonyl)monophosphate(4)를 합성한 후 Mouse leukemia P388, Murine mammary carcinoma FM3A, Human histiocytic lymphoma U937 암세포들에 대해 시험관내 항암활성을 MTT를 이용한 방법으로 예측하고 $IC_{50}$(${\mu}mol/mL$)으로 나타내었다. 그 결과, 비정상적인 염기의 N-3와 당의 C-1' glycoside 결합을 가진 2는 세가지의 암세포에 대해 감수성이 좋아 $IC_{50}$이 각각 0.05, 0.06, 0.06 ${\mu}mol/mL$이었으나 항세균 활성 예측에서는 감수성을 보이지 않았다. Human histiocytic lymphoma U937 세포에 대한 $IC_{50}$은 1이 0.33, 2는 0.66, 3은 0.25 그리고 4는 0.33 ${\mu}mol/mL$로 구조 변화에 따라 서로 다른 값을 보였다

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