scholarly journals Zampanolide and dactylolide: cytotoxic tubulin-assembly agents and promising anticancer leads

2014 ◽  
Vol 31 (9) ◽  
pp. 1202-1226 ◽  
Author(s):  
Qiao-Hong Chen ◽  
David G. I. Kingston
Keyword(s):  
Anticancer Drugs ◽  
Mechanism Of Action ◽  
Potential Mechanism ◽  
New Anticancer Drugs

Zampanolide and its structural relative dactylolide are promising new tubulin-assembly agents with the potential to become new anticancer drugs. This review covers their sources and isolation, structures, anticancer potential, mechanism of action, and syntheses.

scholarly journals Unravelling the Allosteric Targeting of PHGDH at the ACT-Binding Domain with a Photoactivatable Diazirine Probe and Mass Spectrometry Experiments

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 477
Author(s):  
Quentin Spillier ◽  
Séverine Ravez ◽  
Simon Dochain ◽  
Didier Vertommen ◽  
Léopold Thabault ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Anticancer Drugs ◽  
Mechanism Of Action ◽  
Rational Design ◽  
Biosynthetic Pathway ◽  
Allosteric Site ◽  
Site Of Action ◽  
Phosphoglycerate Dehydrogenase ◽  
New Anticancer Drugs

The serine biosynthetic pathway is a key element contributing to tumor proliferation. In recent years, targeting of phosphoglycerate dehydrogenase (PHGDH), the first enzyme of this pathway, intensified and revealed to be a promising strategy to develop new anticancer drugs. Among attractive PHGDH inhibitors are the α-ketothioamides. In previous work, we have demonstrated their efficacy in the inhibition of PHGDH in vitro and in cellulo. However, the precise site of action of this series, which would help the rational design of new inhibitors, remained undefined. In the present study, the detailed mechanism-of-action of a representative α-ketothioamide inhibitor is reported using several complementary experimental techniques. Strikingly, our work led to the identification of an allosteric site on PHGDH that can be targeted for drug development. Using mass spectrometry experiments and an original α-ketothioamide diazirine-based photoaffinity probe, we identified the 523Q-533F sequence on the ACT regulatory domain of PHGDH as the binding site of α-ketothioamides. Mutagenesis experiments further documented the specificity of our compound at this allosteric site. Our results thus pave the way for the development of new anticancer drugs using a completely novel mechanism-of-action.

Pt(II) vs Pd(II) Polyamine Complexes as New Anticancer Drugs: A Structure- Activity Study

2006 ◽  
Vol 3 (3) ◽  
pp. 149-151 ◽  
Author(s):  
S. Fiuza ◽  
A. Amado ◽  
Paulo Oliveira ◽  
Vilma Sardao ◽  
L. de Carvalho ◽  
...  
Keyword(s):  
Anticancer Drugs ◽  
Structure Activity ◽  
New Anticancer Drugs

In the Search for New Anticancer Drugs, III+ Phosphorylated Diaziridine Derivatives

1983 ◽  
Vol 38 (7) ◽  
pp. 884-894 ◽  
Author(s):  
George Sosnovsky ◽  
Jan Lukszo
Keyword(s):  
Anticancer Drugs ◽  
New Anticancer Drugs

Abstract Several N-diethoxyphosphoryl derivatives 7 of various diaziridines, and compounds 12, 15a, 15b, 18 and 20, structurally related to TEPA (1a) and spin labeled Thio-TEPA (1c) were synthesized.

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