Chiral salicyl diamines: potent anticancer molecules.
A set of 12 enantiomeric diamine-based small molecules was synthesized and screened for anticancer activity against five human cancer cell lines: NCI-H460, A549, MCF-7, SK-BR-3, and T-47D. The salicyl diamino compounds (1-6) were found to induce inhibition of the growth of cancer cells at submicromolar concentrations. The lead compound, N,N'-bis-salicyl-(1R,2R)-diaminocyclohexane (1) displayed single-reagent anticancer activity with an IC(50) value equal to or less than 2.0 microM in H460 and A-549 cancer cells. SRB and colony formation assays indicated that compound 1 shows greater cytotoxic activity toward MCF-7 cells than MCF-10A cells. Real-time RT-PCR analysis demonstrated that compound 1, is an extremely efficient regulator of antiapoptotic genes, Bcl-xL, Bcl-2, and the cell cycle related gene, cyclin D1. This study provides a new insight into the development of novel small molecules in the treatment of human breast cancers.
Gao
Jian
J
Department of Chemistry, Texas A&M University, College Station, TX 77843-3255, USA. gaojiantamu@yahoo.com
Liu
Ya-Guang
YG
Zhou
Yaqing
Y
Zingaro
Ralph A
RA
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003959:Diamines / Q000737:chemistry* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D003959:Diamines; D012333:RNA, Messenger