Synthesis and biological evaluation of a water-soluble derivative of the potent V-ATPase inhibitor archazolid

Elke Persch; Teodora Basile; Svenja Bockelmann; Markus Huss; Helmut Wieczorek; Teresa Carlomagno; Dirk Menche

doi:10.1016/j.bmcl.2012.09.081

Synthesis and biological evaluation of a water-soluble derivative of the potent V-ATPase inhibitor archazolid

Bioorg Med Chem Lett. 2012 Dec 15;22(24):7735-8. doi: 10.1016/j.bmcl.2012.09.081. Epub 2012 Oct 13.

Authors

Elke Persch¹, Teodora Basile, Svenja Bockelmann, Markus Huss, Helmut Wieczorek, Teresa Carlomagno, Dirk Menche

Affiliation

¹ Institut für Organische Chemie, Ruprecht-Karls-Universität Heidelberg, INF 270, 69120 Heidelberg, Germany.

PMID: 23122818
DOI: 10.1016/j.bmcl.2012.09.081

Abstract

The water-solubility of the highly potent V-ATPase inhibitors archazolid A and the glucosylated derivative archazolid C was studied in the presence of a wide range of cosolvents, revealing very low solubilites. The first water-soluble analogue was then designed, synthesized, and evaluated for V-ATPase inhibitory activity in vitro.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dose-Response Relationship, Drug
Drug Design
Macrolides / chemical synthesis
Macrolides / chemistry
Macrolides / pharmacology*
Molecular Structure
Solubility
Structure-Activity Relationship
Thiazoles / chemical synthesis
Thiazoles / chemistry
Thiazoles / pharmacology*
Vacuolar Proton-Translocating ATPases / antagonists & inhibitors*
Vacuolar Proton-Translocating ATPases / metabolism
Water / chemistry

Substances

Macrolides
Thiazoles
archazolid A
Water
Vacuolar Proton-Translocating ATPases