Structural determination and in vitro tumor cytotoxicity evaluation of five new cycloartane glycosides from Asplenium ruprechtii Sa. Kurata

Tubulin-targeted chemotherapy has proven to be a successful and wide spectrum strategy against solid and liquid malignancies. Therefore, new ways to modulate this essential protein could lead to new antitumoral pharmacological approaches. Currently known tubulin agents bind to six distinct sites at α/β-tubulin either promoting microtubule stabilization or depolymerization. We have discovered a seventh binding site at the tubulin intradimer interface where a novel microtubule-destabilizing cyclodepsipeptide, termed gatorbulin-1 (GB1), binds. GB1 has a unique chemotype produced by a marine cyanobacterium. We have elucidated this dual, chemical and mechanistic, novelty through multidimensional characterization, starting with bioactivity-guided natural product isolation and multinuclei NMR-based structure determination, revealing the modified pentapeptide with a functionally critical hydroxamate group; and validation by total synthesis. We have investigated the pharmacology using isogenic cancer cell screening, cellular profiling, and complementary phenotypic assays, and unveiled the underlying molecular mechanism by in vitro biochemical studies and high-resolution structural determination of the α/β-tubulin−GB1 complex.

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PERITONEAL MACROPHAGES FROM BCG-INFECTED MICE: TUMOR CYTOTOXICITY AND CHEMOTACTIC RESPONSES IN VITRO

The Macrophage in Neoplasia ◽

10.1016/b978-0-12-256950-0.50022-9 ◽

1976 ◽

pp. 211-225 ◽

Cited By ~ 1

Author(s):

Monte S. Meltzer ◽

Mary M. Stevenson ◽

Robert W. Tucker ◽

Edward J. Leonard

Keyword(s):

Peritoneal Macrophages ◽

Tumor Cytotoxicity

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New Triterpene Glycosides from Camptosorus Sibiricus

Natural Product Communications ◽

10.1177/1934578x1000501008 ◽

2010 ◽

Vol 5 (10) ◽

pp. 1934578X1000501

Author(s):

Ning Li ◽

Wan Xiao ◽

Bailing Hou ◽

Xian Li

Keyword(s):

Human Tumor ◽

2D Nmr ◽

Spectroscopic Methods ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines ◽

Mtt Method ◽

Cycloartane Glycosides ◽

New Compounds

Two new cycloartane glycosides were isolated from the whole herbs of Camptosorus sibiricus Rupr. By means of chemical and spectroscopic methods (1D and 2D NMR, HRMS, ESIMS), the structures were established as (24 R)-3β,7β,24,25,30-pentahydroxycycloartane-30- O-coumaroyl-3- O-β-D-glucopyranosyl-24- O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (1) and (24 R)-3β,7β,24,25,30-pentahydroxy-1-ene-cycloartane 24- O-β-D-glucopyranoside (2). The two new compounds were inactive in vitro against A375-S2 and Hela human tumor cell lines using the MTT method.

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New Cycloartane Glycosides from Camptosorus Sibiricus Rupr

Natural Product Communications ◽

10.1177/1934578x0800300615 ◽

2008 ◽

Vol 3 (6) ◽

pp. 1934578X0800300

Author(s):

Peng Zhang ◽

Yiyu Cheng ◽

Zhongjun Ma

Keyword(s):

Human Tumor ◽

2D Nmr ◽

Spectroscopic Methods ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines ◽

Mtt Method ◽

Cycloartane Glycosides ◽

New Compounds

Two new cycloartane glycosides were isolated from the whole herbs of Camptosorus sibiricus Rupr.. By means of chemical and spectroscopic methods (IR, 1D- and 2D- NMR, HRMS, ESI-MS), the structures were established as (24 R)-3β,7β,24,25,30-pentahydroxycycloartane 3- O-β-D-glucopyranosyl-24- O-β-D-glucopyranosyl-30- O-β-D-glucopyranoside (1), and (24 R)-3β,7β,24,25,30-pentahydroxycycloartane 3- O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-24- O-β-D-xylopyranosyl-(1→2)-β-D-glucopyranoside (2). The two new compounds were tested for their cytotoxicity in vitro against human tumor cell lines (A375-S2, Hela) using the MTT method, but both compounds were inactive.

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