Antineoplastic agents 365. Dolastatin 10 SAR probes

George Pettit; Jayaram K. Srirangam; Jozsef Barkoczy; Michael D. Williams; Michael R. Boyd; Ernest Hamel; Robin Pettit; Fiona Hogan; Ruoli Bai; Jean Chapuis; Shane C. McAllister; Jean M. Schmidt

Antineoplastic agents 365. Dolastatin 10 SAR probes

George Pettit, Jayaram K. Srirangam, Jozsef Barkoczy, Michael D. Williams, Michael R. Boyd, Ernest Hamel, Robin Pettit, Fiona Hogan, Ruoli Bai, Jean Chapuis, Shane C. McAllister, Jean M. Schmidt

Molecular Sciences, School of (SMS)

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

77 Scopus citations

Abstract

The remarkable anticancer drug dolastatin 10 (1a) from the Indian Ocean sea hare Dolabella auricularia is currently undergoing phase I clinical trials. Thirty-eight new structural modifications of this unusual peptide have been synthesized and evaluated against a variety of human and murine cancer cell lines, and for their ability to inhibit tubulin polymerization and vinblastine and GTP binding to tubulin. Dolastatin 10 and one structural modification was found to have antifungal activity, while one other structural modification of the parent compound exhibited antibacterial activity. Some of the new peptides approximated the antineoplastic potency of dolastatin 10, especially those based on replacement of the Doe unit with Met, Phe or an appropriately substituted phenylethylamide.

Original language	English (US)
Pages (from-to)	243-277
Number of pages	35
Journal	Anti-Cancer Drug Design
Volume	13
Issue number	4
State	Published - Jun 1998

Keywords

Antineoplastic agents
Dolastatin 10
Structural modifications

ASJC Scopus subject areas

Biochemistry
Oncology
General Biochemistry, Genetics and Molecular Biology
Pharmacology
Drug Discovery
Organic Chemistry

Cite this

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abstract = "The remarkable anticancer drug dolastatin 10 (1a) from the Indian Ocean sea hare Dolabella auricularia is currently undergoing phase I clinical trials. Thirty-eight new structural modifications of this unusual peptide have been synthesized and evaluated against a variety of human and murine cancer cell lines, and for their ability to inhibit tubulin polymerization and vinblastine and GTP binding to tubulin. Dolastatin 10 and one structural modification was found to have antifungal activity, while one other structural modification of the parent compound exhibited antibacterial activity. Some of the new peptides approximated the antineoplastic potency of dolastatin 10, especially those based on replacement of the Doe unit with Met, Phe or an appropriately substituted phenylethylamide.",

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AU - Pettit, George

AU - Srirangam, Jayaram K.

AU - Barkoczy, Jozsef

AU - Williams, Michael D.

AU - Boyd, Michael R.

AU - Hamel, Ernest

AU - Pettit, Robin

AU - Hogan, Fiona

AU - Bai, Ruoli

AU - Chapuis, Jean

AU - McAllister, Shane C.

AU - Schmidt, Jean M.

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AB - The remarkable anticancer drug dolastatin 10 (1a) from the Indian Ocean sea hare Dolabella auricularia is currently undergoing phase I clinical trials. Thirty-eight new structural modifications of this unusual peptide have been synthesized and evaluated against a variety of human and murine cancer cell lines, and for their ability to inhibit tubulin polymerization and vinblastine and GTP binding to tubulin. Dolastatin 10 and one structural modification was found to have antifungal activity, while one other structural modification of the parent compound exhibited antibacterial activity. Some of the new peptides approximated the antineoplastic potency of dolastatin 10, especially those based on replacement of the Doe unit with Met, Phe or an appropriately substituted phenylethylamide.

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Antineoplastic agents 365. Dolastatin 10 SAR probes

Abstract

Keywords

ASJC Scopus subject areas

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