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Substituted furans as potent lipoxygenase inhibitors: Synthesis,in vitro and molecular docking studies
Affiliation:1. Laboratory of Catalysis and Chemical Biology, Department of Organic and Medicinal Chemistry, CSIR – Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata 700 032, India;2. School of Environmental Studies, Jadavpur University, Kolkata 700 032, India;1. School of Pharmacy, Nanchang University, 461 Bayi Road, Nanchang, Jiangxi, 330006, PR China;2. Center of Analysis and Testing, Nanchang University, Nanchang, 330047, PR China;3. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China;1. Nanjing Medical University, No. 140 HanZhong Road, Nanjing 210029, Jiangsu Province, China;2. Department of Neurosurgery, The Affiliated Brain Hospital of Nanjing Medical University, No. 264 GuangZhou Road, Nanjing 210029, Jiangsu Province, China;3. Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China;4. Department of Neurosurgery, Zhuji Affiliated Hospital of Wenzhou Medical University, China;1. Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Chakdara, 18000 Dir (L), KP, Pakistan;2. Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran, Saudi Arabia;3. Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan;1. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt;2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Egypt;3. Departments of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS, USA;4. Mississippi Center for Excellence in Perinatal Research, University of Mississippi Medical Center, Jackson, MS, USA;5. Women’s Health Research Center, University of Mississippi Medical Center, Jackson, MS, USA;6. Cardio Renal Research Center, University of Mississippi Medical Center, Jackson, MS, USA;7. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia;8. Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Egypt;1. Institute of Chemistry, Baghdad-ul-Jadeed Campus, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Khawaja Fareed Campus, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan;3. Department of Biochemistry, Institute of Biochemistry, Biotechnology and Bioinformatics, Baghdad-ul-Jadeed Campus, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan;4. Department of Chemistry, Division of Sceience and Technology, University of Education, 54770, Lahore, Vehari Campus, Pakistan;5. Department of Chemistry, Government College University Lahore, Lahore 54000, Pakistan;6. Department of Pharmaceutical Biology, Auf der Morgenstelle 8, 72076, University of Tuebingen, Tuebingen, Germany
Abstract:A number of 2-methyl-4-(2-oxo-2-phenyl-ethyl)-5-phenyl-furan-3-carboxylic acid alkyl ester derivatives (3aj) were synthesized and evaluated for their in vitro inhibitory activity on soybean lipoxygenase enzyme. Among the screened compounds, 5-(4-bromo-phenyl)-4-[2-(4-bromo-phenyl)-2-oxo-ethyl]-2-methyl-furan-3-carboxylic acid methyl ester (3g) has been found to exhibit potent inhibitory activity with IC5012.8 μM using nordihydroguaiaretic acid (NDGA) as standard. Molecular modeling was employed for better understanding of the binding between compounds and soybean lipoxygenase enzyme. The predicted binding energy values correlated well with the observed in vitro data.
Keywords:Soybean lipoxygenase  Furan-3-carboxylic acid ester  Molecular docking  Binding energy  Anti-inflammatory
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