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Design and Biological Evaluation of Manganese‐ and Ruthenium‐Based Hybrid CO‐RMs (HYCOs)
Author(s) -
Ollivier Anthony,
Foresti Roberta,
El Ali Zeina,
Martens Thierry,
Kitagishi Hiroaki,
Motterlini Roberto,
Rivard Michael
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900426
Subject(s) - heme oxygenase , chemistry , carbon monoxide , linker , heme , activator (genetics) , molecule , manganese , ruthenium , small molecule , transcription factor , derivative (finance) , enzyme , stereochemistry , combinatorial chemistry , biochemistry , catalysis , organic chemistry , gene , operating system , computer science , financial economics , economics
Interest in the therapeutic effects of carbon monoxide (CO), a product of heme degradation catalyzed by the enzyme heme oxygenase‐1 (HO‐1), has led to the development of CO‐releasing molecules (CO‐RMs) for the controlled delivery of this gas in vivo. We recently proposed conjugating a cobalt‐based CO‐RM with various activators of nuclear factor erythroid 2‐related factor 2 (Nrf2), the transcription factor that regulates HO‐1 expression, in order to exploit the beneficial effects of exogenous and endogenous CO. In this study, we describe the preparation of hybrid molecules (termed HYCOs) conjugating a fumaric acid derivative as an Nrf2 activator to a Mn‐ or a Ru‐based CO‐RM known to be pharmacologically active. With the exception of an acyl‐manganese complex, these hybrids were obtained by associating the two bioactive entities by means of a linker of variable structure. X‐ray diffraction analyses and preliminary biological investigations are also presented.