Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
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Synthesis and Evaluation of Antitumor Activity of 2- and 6-[(1,3- Benzothiazol-2-yl)aminomethyl]-5,8-dimethoxy-1,4-naphthoquinone Derivatives

  • Chung, Yong-Seog (Department of Chemistry, Institute for Basic Science, Chungbuk National University) ;
  • Shin, Young-Kook (Department of Chemistry, Institute for Basic Science, Chungbuk National University) ;
  • Zhan, Chang-Guo (Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky) ;
  • Lee, Sung-Duck (Department of Statistics, Chungbuk National University) ;
  • Cho, Hoon (Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky)
  • Published : 2004.09.01
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Abstract

2- or 6-Substituted BZT-N derivatives were synthesized, and their cytotoxic activity against can-cer L1210 and SNU-1 cells was examined. The antitumor action was also assessed in mice bearing S-180 cells in peritoneal cavity. In a comparison, it was found that 6-substituted BZT-N derivatives exhibited higher potencies in both bioactivities than 2-substituted BZT-N derivatives against L1210 cells in in vitro and S-180 in vitro tests exception of compound 36. Interestingly, it was observed that 2-substituted compound 36, which has methyl group at RI position, exhib-ited a better antitumor activity than 6-substituted compounds against L1210 and SNU-1 in vitro. The EDso value of 2-substituted compound 36 against L1210 was found to be comparable to the EDso value of adriamycin and was even better against the solid cancer cell line SNU-1. It was also observed that 2-substituted compound 36 showed better antitumor activity in mice bearing S-180 cells in the peritoneal cavity. The T/C (％) value of 2-substituted compound 36 was simi-lar to that of adriamycin. Quantitative structure-activity relationship (QSAR) tests reveal that the experimental E $D_{50}$ values against SNU-1 closely correlate with both the calculated HOMO ener-gies ( $E_{HOMO}$) and the measured H-NMR chemical shift of 3-H ($\delta$$_{H}$). The results suggests that a compound having higher $E_{HOMO}$ and $\delta$$_{H}$ values usually should have a lower E $D_{50}$ (SNU-1) value.lue.lue.lue.

Keywords

References

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