TY - JOUR
T1 - Synthesis and cytotoxicity evaluation of substituted pyridazino[4,5-b]phenazine-5,12-diones and tri/tetra-azabenzofluorene-5,6-diones
AU - Lee, Hyun Jung
AU - Kim, Jin Sung
AU - Suh, Myung Eun
AU - Park, Hyen Joo
AU - Lee, Sang Kook
AU - Rhee, Hee Kyung
AU - Kim, Hwa Jung
AU - Seo, Eun Kyung
AU - Kim, Choonmi
AU - Lee, Chong Ock
AU - Park Choo, Hea Young
N1 - Funding Information:
This work was supported by a Korea Research Foundation Grant (KRF-2003-E00004).
PY - 2007/2
Y1 - 2007/2
N2 - 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 (IC50 = 0.097-0.225 μM) against the cancer cell lines. In particular, the cytotoxicity of compounds 7f (R1 = Et) and 7h (R1, R2 = 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.
AB - 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 (IC50 = 0.097-0.225 μM) against the cancer cell lines. In particular, the cytotoxicity of compounds 7f (R1 = Et) and 7h (R1, R2 = 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.
KW - Azabenzo[a]fluorene-5,6-diones
KW - Cytotoxicity
KW - Pyridazino[4,5-b]phenazine-5,12-diones
UR - http://www.scopus.com/inward/record.url?scp=33847155172&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2006.09.007
DO - 10.1016/j.ejmech.2006.09.007
M3 - Article
C2 - 17070967
AN - SCOPUS:33847155172
SN - 0223-5234
VL - 42
SP - 168
EP - 174
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
IS - 2
ER -