Antitumor agents. 166. Synthesis and biological evaluation of 5,6,7,8-substituted-2-phenylthiochromen-4-ones.
As a continuation of our structure--activity relationship study of substituted 2-phenyl-4-quinolones and flavonoids as antitumor and antiviral agents, a series of 5,6,7,8-substituted-2-phenylthiochromen-4-ones has been synthesized by condensation of substituted thiophenols and ethyl benzoylacetates. Target compounds were evaluated for biological activity. Among them, compounds 7, 10, 12, and 13 displayed significant growth inhibitory action against a panel of tumor cell lines including human ileocecal carcinoma (HCT-8), murine leukemia (P-388), human melanoma (RPMI), and human central nervous system tumor (TE671) cells. Compounds 10, 12, and 19 displayed DNA topoisomerase I inhibitory activity in vitro and compound 11 was an in vitro, inhibitor of DNA topoisomerase II. Compound 11 was most active (ED50 value, 0.65 microM) against HIV in acutely infected H9 lymphocytes and had a therapeutic index of about 5.
Wang
H K
HK
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599, USA.
Bastow
K F
KF
Cosentino
L M
LM
Lee
K H
KH
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002839:Chromans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006678:HIV / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D002839:Chromans