Development of 3,5-dinitrobenzoate-based 5-lipoxygenase inhibitors |
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| Affiliation: | 1. Department of Physics, National Institute of Technology, Tiruchirappalli 620015, India;2. Department of Physics, Periyar University, Salem 636011, India;1. Service de Médecine Physique et Réadaptation, Cliniques universitaires Saint-Luc, Brussels, Belgium;2. Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Pneumologie, ORL & Dermatologie, Université Catholique de Louvain, Brussels, Belgium;3. Service de Pneumologie, Cliniques universitaires Saint-Luc, Brussels, Belgium;4. Pediatric Infectious Diseases, Cliniques universitaires Saint-Luc, Brussels, Belgium;5. Pediatric Gastroenterology and Hepatology Department, Cliniques universitaires Saint-Luc, Brussels, Belgium;6. Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Expérimentale et Clinique (IREC), Brussels, Belgium;1. Lennard-Jones Laboratories, School of Physical and Geographical Sciences, Keele University, Staffordshire ST5 5BG, UK;2. Totteridge Institute for Advanced Studies, The Grange, Grange Avenue, London N20 8AB, UK;1. Post Graduate and Research Department of Chemistry, Sri Ramakrishna Mission Vidyalaya College of Arts and Science, Coimbatore 641020, Tamil Nadu, India;2. Department of Physics and Research Centre, Women''s Christian College, Nagarcoil 629001, Tamil Nadu, India;1. Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria, 21321, Egypt;2. Department of Chemistry, Rabigh College of Science and Art, King Abdulaziz University, P.O. Box 344, Rabigh, 21911, Saudi Arabia;3. Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh, 11451, Saudi Arabia;4. Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia |
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| Abstract: | Human 5-lipoxygenase (5-LOX) is a well-validated target for anti-inflammatory therapy. Development of novel 5-LOX inhibitors with higher activities is highly demanded. In previous study, we have built a model for the active conformation of human 5-LOX, and identified naphthalen-1-yl 3,5-dinitrobenzoate (JMC-4) as a 5-LOX inhibitor by virtual screening. In the present work, 3,5-dinitrobenzoate-based 5-lipoxygenase inhibitors were developed. Twenty aryl 3,5-dinitrobenzoates, N-aryl 3,5-dinitrobenzamides and analogues were designed and synthesized. Several of them were found with significantly increased activities according to cell-free assay and human whole blood assay. The structure–activity relationship study may provide useful insights for designing effective 5-LOX inhibitors. |
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| Keywords: | 3,5-Dinitrobenzoate 5-Lipoxygenase inhibitors Cell-free assay Human whole blood assay SAR study |
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