Lee Hyun-Jung, Kim Jin Sung, Suh Myung-Eun, Park Hyen Joo, Lee Sang Kook, Rhee Hee-Kyung, Kim Hwa Jung, Seo Eun-Kyung, Kim Choonmi, Lee Chong-Ock, Park Choo Hea-Young
School of Pharmacy, Ewha Womans University, 11-1 Daehyun-Dong Seodaemun-Ku, Seoul 120-750, South Korea.
Eur J Med Chem. 2007 Feb;42(2):168-74. doi: 10.1016/j.ejmech.2006.09.007. Epub 2006 Oct 27.
The substituted pyridazino[4,5-b]phenazine-5,12-diones and tri/tetra-azabenzo[a]fluorene-5,6-diones were synthesized from 6,7-dichlorophthalazine-5,8-dione and 6,7-dichloroquinoline-5,8-dione, respectively. The cytotoxic activities of the prepared compounds were evaluated by an SRB (Sulforhodamine B) assay against the following human cancer cell lines: A549 (lung), SK-OV-3 (ovarian), SK-MEL-2 (melanoma), XF 498 (CNS), and HCT 15 (colon). Almost all synthesized pyridazino[4,5-b]phenazine-5,12-diones (7a-j) presented higher cytotoxicity than that of doxorubicin (IC(50)=0.097-0.225 microM) against the cancer cell lines. In particular, the cytotoxicity of compounds 7f (R(1)=Et) and 7h (R(1), R(2)=Me) against all human cancer cell lines examined was about 10 times higher than that of doxorubicin. However, the cytotoxicities of several synthesized azabenzo[a]fluorene-5,6-diones (12a, 12c, 12d, 12e, and 12g) against the cancer cell lines in vitro were comparable to those of doxorubicin.
取代哒嗪并[4,5 - b]菲嗪 - 5,12 - 二酮和三/四氮杂苯并[a]芴 - 5,6 - 二酮分别由6,7 - 二氯酞嗪 - 5,8 - 二酮和6,7 - 二氯喹啉 - 5,8 - 二酮合成。通过SRB（磺酰罗丹明B）测定法评估所制备化合物对以下人类癌细胞系的细胞毒性活性：A549（肺癌）、SK - OV - 3（卵巢癌）、SK - MEL - 2（黑色素瘤）、XF 498（中枢神经系统癌）和HCT 15（结肠癌）。几乎所有合成的哒嗪并[4,5 - b]菲嗪 - 5,12 - 二酮（7a - j）对癌细胞系的细胞毒性都高于阿霉素（IC(50)=0.097 - 0.225 microM）。特别是，化合物7f（R(1)=Et）和7h（R(1), R(2)=Me）对所有检测的人类癌细胞系的细胞毒性比阿霉素高约10倍。然而，几种合成的氮杂苯并[a]芴 - 5,6 - 二酮（12a、12c、12d、12e和12g）在体外对癌细胞系的细胞毒性与阿霉素相当。
