TY - JOUR
T1 - Chiral salicyl diamines
T2 - Potent anticancer molecules
AU - Gao, Jian
AU - Liu, Ya Guang
AU - Zhou, Yaqing
AU - Zingaro, Ralph A.
PY - 2007/12/10
Y1 - 2007/12/10
N2 - 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 IC50 value equal to or less than 2.0 μM 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.
AB - 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 IC50 value equal to or less than 2.0 μM 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.
KW - Bcl-xL expression
KW - Chiral cyclohexyldiamines
KW - Cytotoxic activity
KW - Human breast cancer cells
KW - Small molecules
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U2 - 10.1002/cmdc.200700049
DO - 10.1002/cmdc.200700049
M3 - Article
C2 - 17943711
AN - SCOPUS:48849101856
SN - 1860-7179
VL - 2
SP - 1723
EP - 1729
JO - ChemMedChem
JF - ChemMedChem
IS - 12
ER -