Antineoplastic agents. 600. from the south pacific ocean to the silstatins

George Pettit; Pablo M. Arce; Jean Chapuis; Christian B. Macdonald

doi:10.1021/np501004h

Antineoplastic agents. 600. from the south pacific ocean to the silstatins

George Pettit, Pablo M. Arce, Jean Chapuis, Christian B. Macdonald

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

4 Scopus citations

Abstract

The recent advances in the development of antibody and other drug conjugates for targeted cancer treatment have further increased the need for powerful cancer cell growth inhibitors. Toward that objective we have extended our earlier discovery of the remarkable anticancer bacillistatins 1 and 2 from Bacillus silvestris to SAR and other structural modifications such as availability of a free hydroxy group for antibody-drug conjugate (ADC) and other prodrug linkage. That direction has resulted in seven structural modifications designated silstatins 1-8 (7a, 8a, 8b, 14a, 15a, 15b, 18a, and 18b), where the exceptional cancer cell growth inhibition of some of them are in the range GI₅₀ 10^-3-10^-4 μM/mL. Silstatin 7 (18a) was converted to a glucuronic conjugate (28) that displayed an impressive reduction in toxicity during transport.

Original language	English (US)
Pages (from-to)	510-523
Number of pages	14
Journal	Journal of Natural Products
Volume	78
Issue number	3
DOIs	https://doi.org/10.1021/np501004h
State	Published - Mar 27 2015

ASJC Scopus subject areas

Analytical Chemistry
Molecular Medicine
Pharmacology
Pharmaceutical Science
Drug Discovery
Complementary and alternative medicine
Organic Chemistry

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10.1021/np501004h

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abstract = "The recent advances in the development of antibody and other drug conjugates for targeted cancer treatment have further increased the need for powerful cancer cell growth inhibitors. Toward that objective we have extended our earlier discovery of the remarkable anticancer bacillistatins 1 and 2 from Bacillus silvestris to SAR and other structural modifications such as availability of a free hydroxy group for antibody-drug conjugate (ADC) and other prodrug linkage. That direction has resulted in seven structural modifications designated silstatins 1-8 (7a, 8a, 8b, 14a, 15a, 15b, 18a, and 18b), where the exceptional cancer cell growth inhibition of some of them are in the range GI50 10-3-10-4 μM/mL. Silstatin 7 (18a) was converted to a glucuronic conjugate (28) that displayed an impressive reduction in toxicity during transport.",

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AU - Pettit, George

AU - Arce, Pablo M.

AU - Chapuis, Jean

AU - Macdonald, Christian B.

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Antineoplastic agents. 600. from the south pacific ocean to the silstatins

Abstract

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