Collaborative Paper published in “Bioorganic & Medicinal Chemistry”

/ June 27, 2011/ News, Research

Researchers of Leipzig and Vanderbilt Universities published a paper in the journal “Bioorganic & Medicinal Chemistry” showing the results of their collaborative project on carbaborane research. The paper, published in March 2011, describes new synthesis strategies of indomethacin derivatives with inorganic carbaborane clusters. Indomethacin is a very potent cyclooxygenase (COX)-1 and COX-2 inhibitor with clinical significance as anti-inflammatory drug , The carbaborane-modified drug candidates showed also COX inhibition activity, depending on the carbaborane isomer and the connection pattern. The results gave general insights into the applicability of carbaboranes as drug entities.

Synthesis and evaluation of carbaborane derivatives of indomethacin as cyclooxygenase inhibitors

Matthias Scholz(1), Anna L. Blobaum(2), Lawrence J. Marnett(2) and Evamarie Hey-Hawkins(1)

(1) Institut für Anorganische Chemie der Universität Leipzig, Johannisallee 29, 04103 Leipzig, Germany

(2) A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute for Chemical Biology and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA

Bioorganic & Medicinal Chemistry. Volume 19, Issue 10, 15 May 2011, Pages 3242-3248

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their pharmacological activities by inhibiting cyclooxygenase (COX)-1 and COX-2. Previous studies have shown that esters and amides of non-selective inhibitors such as indomethacin are selective against COX-2, which is the therapeutically relevant isoform. Structure–activity analysis indicates that substituted phenyl rings are tolerated as ester components. In the present study, the introduction of inorganic ortho– and meta-carbaborane moieties was explored with the aim to create COX-2 inhibitors and more importantly to investigate the validity of using these boron clusters as drug entities. Interestingly, only the ortho-carbaborane ester was active whereas the meta isomer was not. A similar lack of inhibitory potency was observed when an adamantyl substituent or alkylene spacers at the carbaborane were introduced in the ester functionality.

Link to paper