New Insight into the SAR of Pyrimido [4,5-b][1,4] Benzothiazines as 15-lipoxygenase Inhibitors | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 8، دوره 16، شماره 6، شهریور 2013، صفحه 784-789 اصل مقاله (513.62 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2013.995 | ||
| نویسندگان | ||
| Nona Pooryaghoobi1؛ Mehdi Bakavoli2؛ Maliheh Alimardani3؛ Tahmineh Bazzazan4؛ Hamid Sadeghian* 5 | ||
| 11Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, IR Iran | ||
| 2Department of Chemistry, School of Sciences, Ferdowsi University of Mashhad, Mashhad, 917751436, IR Iran | ||
| 3Student Research Committee, Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, IR Iran | ||
| 42Department of Chemistry, School of Sciences, Ferdowsi University of Mashhad, Mashhad, 917751436, IR Iran | ||
| 5Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad 91967-73117, IR Iran 5 Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, IR Iran | ||
| چکیده | ||
| Objective(s): Recently we reported that the soybean 15-lipoxygenase (SLO) inhibitory activity of pyrimido[4,5-b][l,4]benzothiazines largely depends on the orientation of sulfur atom of thiazine core towards FeIII-OH in the active site pocket of the enzyme with subsequent oxidation of sulfur to sulfoxide. In this paper the results of a comparative study on the SLO inhibitory activities of the mentioned compounds using ab initio calculations and docking analyses has been reported. Materials and Methods: Structure optimization and docking analyses were performed using HyperChem 7.5 and AutoDock Tools 4.0 respectively. Enzyme assessment was reduced using spectrophotometric MBTH-DMAB method. Results : The inhibitory activity of synthetic 2-substituted pyrimido[4,5-b][l,4]benzothiazines against soybean 15-lipoxygenase (SLO) was evaluated and structure activity relationships and binding modes of their 4-H and 4-methyl analogs were studied using docking analysis and ab initio calculations. Discussion: The results of these studies showed that the lack of 4-methyl substituent in the pyrimido[4,5-b][1,4]benzothiazine molecules greatly reduces their lipoxygenase inhibitory activities and it was also found that the HOMO energy difference between the 4-H and 4-Methyl analogs can be responsible for the observed inhibitory activity reduction. Conclusion: Our molecular modeling studies shows that by using more flexible amino acids during the docking process, more rational results can be obtained. The method of measuring the lipoxygenase activity is also of prime importance for the study of structure activity relationship. | ||
| کلیدواژهها | ||
| DMAB Docking MBTH Peroxide formation SLO | ||
| مراجع | ||
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SAR of Pyrimidobenzothiazines as 15-LO Inhibitors
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