Cytotoxic activity of (S)-goniothalamin and analogues against human cancer cells.
(R)- and (S)-Goniothalamin (1) and analogues 2-9 were efficiently prepared in high overall yield and enantiomeric purity, and their cytotoxic activities were evaluated against eight human cancer cell lines. A structure-activity relationship study (SAR) allowed us to establish the relevant structural features for the cytotoxic activity of goniothalamin analogues. In addition, we have identified non-natural form of goniothalamin (S)-1 and analogue 5 as the highest and more selective cytotoxic compounds against kidney cancer cell growth (786-0) with IC50 = 4 and 5 nM, respectively, and compound 8 (IC50 = 4 nM) as the more potent against breast cancer cells with resistance phenotype for adryamycin (NCI.ADR).
Fátima
Angelo de
Ad
Instituto de Química, Unicamp, CP 6154, 13084-971, Campinas, São Paulo, Brazil.
Kohn
Luciana K
LK
Carvalho
João Ernesto de
JE
Pilli
Ronaldo A
RA
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D011753:Pyrones / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D011753:Pyrones; C103280:goniothalamin; D004317:Doxorubicin