Myeloperoxidase Inhibitors as Potential Drugs
Апстракт
Myeloperoxidase (MPO) is an important member of the haem peroxidase - cyclooxygenase superfamily. This enzyme is physiologically expressed in circulating neutrophils, monocytes and some tissue macrophages including microglia. MPO plays an essential role in the antimicrobial and antiviral system of humans. The microbicidal activity of MPO exists due to its capability to oxidize halide and pseudohalide ions (Cl-, Br-, I- and SCN-) by H2O2, thereby producing respective hypohalous acids (HOX). During the phagocytosis of pathogens, azurophilic granules release their content together with MPO into phagolysosomes. On the other hand, MPO can be discharged outside the phagocytes. Due to this, tissue damage during inflammation is greatly promoted by MPO-derived oxidants. Regarding its activity, MPO is a key factor in a great number of conditions within the group of cardiovascular diseases, inflammatory diseases, neurodegenerative diseases, kidney diseases and immune-mediated diseases. Therefore,... MPO and its downstream inflammatory pathways might be attractive targets for both prognostic and therapeutic intervention in the prophylaxis of all mentioned illnesses. Nowadays, structure and reaction mechanism of MPO are known, which enable rational strategy in the development of specific MPO inhibitors that still preserve MPO activity during host defense from bacteria, but hinder pathophysiologically persistent activation of MPO. Various methods for MPO activity inhibition and unfavorable effects of MPO-derived oxidants remodeling will be discussed. Emphasis will be put on various known inhibitors, as well as on newly investigated natural products, which can also inhibit MPO activity.
Кључне речи:
Atherosclerosis / cardiovascular / inflammation / inhibitors / myeloperoxidase / therapeuticsИзвор:
Current Drug Metabolism, 2015, 16, 3, 168-190Финансирање / пројекти:
- Истраживања интеракција ензима са токсичним и фармаколошки активним молекулима (RS-MESTD-Basic Research (BR or ON)-172023)
DOI: 10.2174/138920021603150812120640
ISSN: 1389-2002; 1875-5453
PubMed: 26279325
WoS: 000359604700001
Scopus: 2-s2.0-84940877224
Колекције
Институција/група
VinčaTY - JOUR AU - Lazarević-Pašti, Tamara AU - Leskovac, Andreja AU - Vasić, Vesna M. PY - 2015 UR - https://vinar.vin.bg.ac.rs/handle/123456789/700 AB - Myeloperoxidase (MPO) is an important member of the haem peroxidase - cyclooxygenase superfamily. This enzyme is physiologically expressed in circulating neutrophils, monocytes and some tissue macrophages including microglia. MPO plays an essential role in the antimicrobial and antiviral system of humans. The microbicidal activity of MPO exists due to its capability to oxidize halide and pseudohalide ions (Cl-, Br-, I- and SCN-) by H2O2, thereby producing respective hypohalous acids (HOX). During the phagocytosis of pathogens, azurophilic granules release their content together with MPO into phagolysosomes. On the other hand, MPO can be discharged outside the phagocytes. Due to this, tissue damage during inflammation is greatly promoted by MPO-derived oxidants. Regarding its activity, MPO is a key factor in a great number of conditions within the group of cardiovascular diseases, inflammatory diseases, neurodegenerative diseases, kidney diseases and immune-mediated diseases. Therefore, MPO and its downstream inflammatory pathways might be attractive targets for both prognostic and therapeutic intervention in the prophylaxis of all mentioned illnesses. Nowadays, structure and reaction mechanism of MPO are known, which enable rational strategy in the development of specific MPO inhibitors that still preserve MPO activity during host defense from bacteria, but hinder pathophysiologically persistent activation of MPO. Various methods for MPO activity inhibition and unfavorable effects of MPO-derived oxidants remodeling will be discussed. Emphasis will be put on various known inhibitors, as well as on newly investigated natural products, which can also inhibit MPO activity. T2 - Current Drug Metabolism T1 - Myeloperoxidase Inhibitors as Potential Drugs VL - 16 IS - 3 SP - 168 EP - 190 DO - 10.2174/138920021603150812120640 ER -
@article{ author = "Lazarević-Pašti, Tamara and Leskovac, Andreja and Vasić, Vesna M.", year = "2015", abstract = "Myeloperoxidase (MPO) is an important member of the haem peroxidase - cyclooxygenase superfamily. This enzyme is physiologically expressed in circulating neutrophils, monocytes and some tissue macrophages including microglia. MPO plays an essential role in the antimicrobial and antiviral system of humans. The microbicidal activity of MPO exists due to its capability to oxidize halide and pseudohalide ions (Cl-, Br-, I- and SCN-) by H2O2, thereby producing respective hypohalous acids (HOX). During the phagocytosis of pathogens, azurophilic granules release their content together with MPO into phagolysosomes. On the other hand, MPO can be discharged outside the phagocytes. Due to this, tissue damage during inflammation is greatly promoted by MPO-derived oxidants. Regarding its activity, MPO is a key factor in a great number of conditions within the group of cardiovascular diseases, inflammatory diseases, neurodegenerative diseases, kidney diseases and immune-mediated diseases. Therefore, MPO and its downstream inflammatory pathways might be attractive targets for both prognostic and therapeutic intervention in the prophylaxis of all mentioned illnesses. Nowadays, structure and reaction mechanism of MPO are known, which enable rational strategy in the development of specific MPO inhibitors that still preserve MPO activity during host defense from bacteria, but hinder pathophysiologically persistent activation of MPO. Various methods for MPO activity inhibition and unfavorable effects of MPO-derived oxidants remodeling will be discussed. Emphasis will be put on various known inhibitors, as well as on newly investigated natural products, which can also inhibit MPO activity.", journal = "Current Drug Metabolism", title = "Myeloperoxidase Inhibitors as Potential Drugs", volume = "16", number = "3", pages = "168-190", doi = "10.2174/138920021603150812120640" }
Lazarević-Pašti, T., Leskovac, A.,& Vasić, V. M.. (2015). Myeloperoxidase Inhibitors as Potential Drugs. in Current Drug Metabolism, 16(3), 168-190. https://doi.org/10.2174/138920021603150812120640
Lazarević-Pašti T, Leskovac A, Vasić VM. Myeloperoxidase Inhibitors as Potential Drugs. in Current Drug Metabolism. 2015;16(3):168-190. doi:10.2174/138920021603150812120640 .
Lazarević-Pašti, Tamara, Leskovac, Andreja, Vasić, Vesna M., "Myeloperoxidase Inhibitors as Potential Drugs" in Current Drug Metabolism, 16, no. 3 (2015):168-190, https://doi.org/10.2174/138920021603150812120640 . .