Synthesis of A83586C analogs with potent anticancer and beta-catenin/ TCF4/osteopontin inhibitory effects and insights into how A83586C modulates E2Fs and pRb.

Karl J Hale; S. Manaviazar; L. Lazarides; J. George; M.A. Walters; J. Cai; V.M. Delisser; G.S. Bhatia; S.A. Peak; S.M. Dalby; A. Lefranc; Y.P. Chen; A.W. Wood; Paul Crowe; Pauline Erwin; Mohamed El-Tanani

doi:10.1021/ol802818f

Synthesis of A83586C analogs with potent anticancer and beta-catenin/ TCF4/osteopontin inhibitory effects and insights into how A83586C modulates E2Fs and pRb.

Karl J Hale, S. Manaviazar, L. Lazarides, J. George, M.A. Walters, J. Cai, V.M. Delisser, G.S. Bhatia, S.A. Peak, S.M. Dalby, A. Lefranc, Y.P. Chen, A.W. Wood, Paul Crowe, Pauline Erwin, Mohamed El-Tanani

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

The synthesis of three potent new antitumor agents is described: the A83586C-citropeptin hybrid (1), the A83586C-GE3 hybrid (2), and l-Pro-A83586C (3). Significantly, compounds 1 and 2 function as highly potent inhibitors of ß-catenin/TCF4 signaling within cancer cells, while simultaneously downregulating osteopontin (Opn) expression. A83586C antitumor cyclodepsipeptides also inhibit E2F-mediated transcription by downregulating E2F1 expression and inducing dephosphorylation of the oncogenic hyperphosphorylated retinoblastoma protein (pRb).

Original language	English
Pages (from-to)	737-740
Number of pages	4
Journal	Organic Letters
Volume	11
Issue number	3
DOIs	https://doi.org/10.1021/ol802818f
Publication status	Published - 05 Feb 2009

ASJC Scopus subject areas

Biochemistry
Organic Chemistry
Physical and Theoretical Chemistry

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10.1021/ol802818f

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Hale, K. J., Manaviazar, S., Lazarides, L., George, J., Walters, M. A., Cai, J., Delisser, V. M., Bhatia, G. S., Peak, S. A., Dalby, S. M., Lefranc, A., Chen, Y. P., Wood, A. W., Crowe, P., Erwin, P., & El-Tanani, M. (2009). Synthesis of A83586C analogs with potent anticancer and beta-catenin/ TCF4/osteopontin inhibitory effects and insights into how A83586C modulates E2Fs and pRb. Organic Letters, 11(3), 737-740. https://doi.org/10.1021/ol802818f

Hale, Karl J ; Manaviazar, S. ; Lazarides, L. ; George, J. ; Walters, M.A. ; Cai, J. ; Delisser, V.M. ; Bhatia, G.S. ; Peak, S.A. ; Dalby, S.M. ; Lefranc, A. ; Chen, Y.P. ; Wood, A.W. ; Crowe, Paul ; Erwin, Pauline ; El-Tanani, Mohamed. / Synthesis of A83586C analogs with potent anticancer and beta-catenin/ TCF4/osteopontin inhibitory effects and insights into how A83586C modulates E2Fs and pRb. In: Organic Letters. 2009 ; Vol. 11, No. 3. pp. 737-740.

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title = "Synthesis of A83586C analogs with potent anticancer and beta-catenin/ TCF4/osteopontin inhibitory effects and insights into how A83586C modulates E2Fs and pRb.",

abstract = "The synthesis of three potent new antitumor agents is described: the A83586C-citropeptin hybrid (1), the A83586C-GE3 hybrid (2), and l-Pro-A83586C (3). Significantly, compounds 1 and 2 function as highly potent inhibitors of {\ss}-catenin/TCF4 signaling within cancer cells, while simultaneously downregulating osteopontin (Opn) expression. A83586C antitumor cyclodepsipeptides also inhibit E2F-mediated transcription by downregulating E2F1 expression and inducing dephosphorylation of the oncogenic hyperphosphorylated retinoblastoma protein (pRb).",

author = "Hale, {Karl J} and S. Manaviazar and L. Lazarides and J. George and M.A. Walters and J. Cai and V.M. Delisser and G.S. Bhatia and S.A. Peak and S.M. Dalby and A. Lefranc and Y.P. Chen and A.W. Wood and Paul Crowe and Pauline Erwin and Mohamed El-Tanani",

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doi = "10.1021/ol802818f",

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Hale, KJ, Manaviazar, S, Lazarides, L, George, J, Walters, MA, Cai, J, Delisser, VM, Bhatia, GS, Peak, SA, Dalby, SM, Lefranc, A, Chen, YP, Wood, AW, Crowe, P , Erwin, P & El-Tanani, M 2009, 'Synthesis of A83586C analogs with potent anticancer and beta-catenin/ TCF4/osteopontin inhibitory effects and insights into how A83586C modulates E2Fs and pRb.', Organic Letters, vol. 11, no. 3, pp. 737-740. https://doi.org/10.1021/ol802818f

Synthesis of A83586C analogs with potent anticancer and beta-catenin/ TCF4/osteopontin inhibitory effects and insights into how A83586C modulates E2Fs and pRb. / Hale, Karl J; Manaviazar, S.; Lazarides, L.; George, J.; Walters, M.A.; Cai, J.; Delisser, V.M.; Bhatia, G.S.; Peak, S.A.; Dalby, S.M.; Lefranc, A.; Chen, Y.P.; Wood, A.W.; Crowe, Paul ; Erwin, Pauline; El-Tanani, Mohamed.

In: Organic Letters, Vol. 11, No. 3, 05.02.2009, p. 737-740.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Synthesis of A83586C analogs with potent anticancer and beta-catenin/ TCF4/osteopontin inhibitory effects and insights into how A83586C modulates E2Fs and pRb.

AU - Hale, Karl J

AU - Manaviazar, S.

AU - Lazarides, L.

AU - George, J.

AU - Walters, M.A.

AU - Cai, J.

AU - Delisser, V.M.

AU - Bhatia, G.S.

AU - Peak, S.A.

AU - Dalby, S.M.

AU - Lefranc, A.

AU - Chen, Y.P.

AU - Wood, A.W.

AU - Crowe, Paul

AU - Erwin, Pauline

AU - El-Tanani, Mohamed

PY - 2009/2/5

Y1 - 2009/2/5

N2 - The synthesis of three potent new antitumor agents is described: the A83586C-citropeptin hybrid (1), the A83586C-GE3 hybrid (2), and l-Pro-A83586C (3). Significantly, compounds 1 and 2 function as highly potent inhibitors of ß-catenin/TCF4 signaling within cancer cells, while simultaneously downregulating osteopontin (Opn) expression. A83586C antitumor cyclodepsipeptides also inhibit E2F-mediated transcription by downregulating E2F1 expression and inducing dephosphorylation of the oncogenic hyperphosphorylated retinoblastoma protein (pRb).

AB - The synthesis of three potent new antitumor agents is described: the A83586C-citropeptin hybrid (1), the A83586C-GE3 hybrid (2), and l-Pro-A83586C (3). Significantly, compounds 1 and 2 function as highly potent inhibitors of ß-catenin/TCF4 signaling within cancer cells, while simultaneously downregulating osteopontin (Opn) expression. A83586C antitumor cyclodepsipeptides also inhibit E2F-mediated transcription by downregulating E2F1 expression and inducing dephosphorylation of the oncogenic hyperphosphorylated retinoblastoma protein (pRb).

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JO - Organic Letters

JF - Organic Letters

SN - 1523-7060

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