Generation of Carbon Monoxide Releasing Molecules (CO-RMs) as Drug Candidates for the Treatment of Acute Liver Injury: Targeting of CO-RMs to the Liver
| Autor: | David Gallo, Lukas Adrian Kromer, Isabel Bento, Ana R. Marques, Gonçalo J. L. Bernardes, Marta Norton De Matos, Sherrie L. Otterbein, Ana S. G. Gonçalves, Nuno Penacho, João Seixas, Ana M. L. Gonçalves, Sandra Rodrigues, Rachel A. Ruggieri, Walter Anton Blättler, Patrícia M. Reis, Leo E. Otterbein, Carlos C. Romão |
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| Rok vydání: | 2012 |
| Předmět: |
Drug
media_common.quotation_subject Organic Chemistry chemistry.chemical_element Carbon monoxide-releasing molecules Combinatorial chemistry Inorganic Chemistry chemistry.chemical_compound chemistry Myoglobin In vivo Molybdenum Organic chemistry Molecule Hemoglobin Physical and Theoretical Chemistry Carbon monoxide media_common |
| Zdroj: | Organometallics. 31:5810-5822 |
| ISSN: | 1520-6041 0276-7333 |
| DOI: | 10.1021/om300360c |
| Popis: | The discovery of the biological effects of carbon monoxide (CO) in recent years strongly suggests that CO could find applications as a therapeutic agent. CO is a highly toxic gas when used at industrial doses, due in part to its binding affinity to hemoglobin. Since hemoglobin binds CO with the highest affinity in vivo, it also constitutes a major barrier to the delivery of CO to tissues in need of therapy. A method of delivering CO that can bypass hemoglobin is the use of pro-drugs or CO carriers, called CO-releasing molecules (CO-RMs) that become activated and release CO in tissues in need of treatment. Organometallic carbonyl complexes are best suited to play the role of CO carriers, and indeed the natural CO carrier molecules hemoglobin and myoglobin belong to this class of chemical compounds. Here we describe the preparation of novel molybdenum CO-RMs of general formula Mo(CO)3(CNCR′R″CO2R‴)3 (R′, R″ = H, Me, iPr, CH2Ph, CO2Li, −CH2CH2–, −CH2(CH2)3CH2–; R‴ = H, Li), which present favorable druglike c... |
| Databáze: | OpenAIRE |
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