Synthesis and evaluation of antitumor activity of 2- and 6-[(1,3-benzothiazol-2-yl)aminomethyl]-5,8-dimethoxy-1,4-naphthoquinone derivatives.
2- or 6-substituted BZT-N derivatives were synthesized, and their cytotoxic activity against cancer 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 R1 position, exhibited a better antitumor activity than 6-substituted compounds against L1210 and SNU-1 in vitro. The ED50 value of 2-substituted compound 36 against L1210 was found to be comparable to the ED50 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 similar to that of adriamycin. Quantitative structure-activity relationship (QSAR) tests reveal that the experimental ED50 values against SNU-1 closely correlate with both the calculated HOMO energies (E(HOMO)) and the measured 1H-NMR chemical shift of 3-H (deltaH). The results suggests that a compound having higher E(HOMO) and deltaH values usually should have a lower ED50 (SNU-1) value.
Department of Chemistry, Institute for Basic Science, Chungbuk National University, Chungbuk 361-763, Korea. yschung@chungbuk.ac.kr
Yongseog
Y
Chung
Young-Kook
YK
Shin
Chang-Guo
CG
Zhan
Sungduck
S
Lee
Hoon
H
Cho
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D052160:Benzothiazoles; D002522:Chlorocebus aethiops; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D007939:Leukemia L1210; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000627:therapeutic use; D012510:Sarcoma 180 / Q000188:drug therapy; D013844:Thiazoles / Q000138:chemical synthesis* / Q000627:therapeutic use; D014709:Vero Cells
D000970:Antineoplastic Agents; D052160:Benzothiazoles; D009285:Naphthoquinones; D013844:Thiazoles; C005465:benzothiazole