Synthesis and cytotoxicity evaluation of substituted pyridazino[4,5-b]phenazine-5,12-diones and tri/tetra-azabenzofluorene-5,6-diones.
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.
Lee
Hyun-Jung
HJ
School of Pharmacy, Ewha Womans University, 11-1 Daehyun-Dong Seodaemun-Ku, Seoul 120-750, South Korea.
Kim
Jin Sung
JS
Suh
Myung-Eun
ME
Park
Hyen Joo
HJ
Lee
Sang Kook
SK
Rhee
Hee-Kyung
HK
Kim
Hwa Jung
HJ
Seo
Eun-Kyung
EK
Kim
Choonmi
C
Lee
Chong-Ock
CO
Park Choo
Hea-Young
HY
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005449:Fluorenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D010619:Phenazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D005449:Fluorenes; D010619:Phenazines; D011724:Pyridazines