Dehydrozingerone, chalcone, and isoeugenol analogues as in vitro anticancer agents.
Twenty-eight compounds related to dehydrozingerone (1), isoeugenol (3), and 2-hydroxychalcone (4) were synthesized and evaluated in vitro against human tumor cell replication. Except for isoeugenol analogues 27-35, most compounds exhibited moderate or strong cytotoxic activity against KB, KB-VCR (a multidrug-resistant derivative), and A549 cell lines. In particular, chalcone 15 showed significant cytotoxic activity against the A549 cell line with an IC50 value of 0.6 microg/mL. Furthermore, dehydrozingerone analogue 11 and chalcones 16 and 17 showed significant and similar cytotoxic activity against both KB (IC50 values of 2.0, 1.0, and 2.0 microg/mL, respectively) and KB-VCR (IC50 values of 1.9, 1.0, and 2.0 microg/mL, respectively) cells, suggesting that they are not substrates for the P-glycoprotein drug efflux pump.
Tatsuzaki
Jin
J
Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599-7360, USA.
Bastow
Kenneth F
KF
Nakagawa-Goto
Kyoko
K
Nakamura
Seiko
S
Itokawa
Hideji
H
Lee
Kuo-Hsiung
KH
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005054:Eugenol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D013343:Styrenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D047188:Chalcones; D013343:Styrenes; D005054:Eugenol; C036643:isoeugenol; C052933:methyl-3-methoxy-4-hydroxystyryl ketone