1-(2-Hydroxy-5-((trimethylsilyl)ethynyl)phenyl)ethanone based α,β-unsaturated derivatives an alternate to non-sulfonamide carbonic anhydrase II inhibitors,synthesis via Sonogashira coupling,binding analysis,Lipinsk’s rule validation |
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| Institution: | 1. Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan;2. Department of Chemistry, School of Optics/Center for Research and Education in Optics and Lasers University of Central Florida, P.O. Box 162366, Orlando, FL 32816, United States;3. Institute of Biochemistry, University of Sindh, Jamshoro 76080, Pakistan;4. Department of Physiology, University of Sindh, Jamshoro 76080, Pakistan;5. Department of Biological Sciences, College of Natural Sciences, Kongju National University, 56 Gongjudehak-Ro, Gongju, Chungnam 314-701, Republic of Korea;1. Department of Chemistry, Kongju National University, Gongju, Chungnam, 32588, Republic of Korea;2. Department of Biological Sciences, Kongju National University, Gongju, Chungnam, 32588, Republic of Korea;3. Institute of Molecular Biology and Biotechnology, The University of Lahore, Defence Road, Lahore, 54590, Pakistan;4. Center for Chemical Analysis, Korea Research Institute of Chemical Technology, Yuseong, Daejeon, 34114, Republic of Korea;1. Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Raiwind Road, 55150 Lahore, Pakistan;2. Department of Chemistry, Government College University, Lahore 54000, Pakistan;3. Institute of Molecular Science and Bioinformatics, Nisbat Road, Lahore, Pakistan;4. College of Natural Science, Department of Biological Sciences, Kongju National University, Gongju 32588, South Korea;5. Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia;6. Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Level 9, FF3, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia;7. Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan;8. Department of Biochemistry, University of Agriculture, Faisalabad 38040, Pakistan;1. Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan;2. Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic;3. Department of Biological Sciences, College of Natural Sciences, Kongju National University, 56 Gongjudehak-Ro, Gongju, Chungnam 314-701, Republic of Korea;4. Institute of biochemistry, University of Sindh, Jamshoro 76080, Pakistan;5. Cardiovascular and Metabolic Research Unit, Laurentian University, 935 Ramsey Lake Road, Sudbury, ON P3E 2C6, Canada;6. Department of Chemistry, Abdul Wali Khan University, Mardan, Khybder Pakhtunkhwa, Pakistan;7. Department of Physiology, University of Sindh, Jamshoro 76080, Pakistan;1. Sulaiman Bin Abdullah Aba Al-Khail-Centre for Interdisciplinary Research in Basic Sciences (SA-CIRBS), International Islamic University 44000 Islamabad, Pakistan;2. School of Chemistry and Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom;3. Department of Chemistry, Quaid-i-Azam University 45320 Islamabad, Pakistan;4. Department of Biological Sciences, College of Natural Science, Kongju National University, Gongju 32588, Republic of Korea;5. Department of Physiology, University of Sindh, Jamshoro, Pakistan;1. College of Natural Science, Department of Biological Sciences, Kongju National University, Gongju 32588, South Korea;2. Department of Chemistry, Government College University, Lahore 54000, Pakistan;3. Faculty of Pharmacy, Level 9, FF3, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia;4. Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Level 9, FF3, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia;1. College of Natural Science, Department of Biological Sciences, Kongju National University, Gongju, 32588, South Korea;2. Department of Chemistry, Government College University, Lahore, 54000, Pakistan;3. Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, 54000, Pakistan;4. Faculty of Pharmacy, Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, 42300, Bandar Puncak Alam, Selangor D. E., Malaysia;5. Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, 42300, Bandar Puncak Alam, Selangor D. E., Malaysia;6. Department of Biochemistry, University of Agriculture, Faisalabad, 38040, Pakistan |
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| Abstract: | A novel series of silyl-yne containing chalcone derivatives 5a-5j was synthesized by exploiting Sonogashira coupling reaction and Claisen-Schimdt condensation reaction. The synthesized derivative were characterized by spectroscopic and elemental analysis. The selective inhibition of carbonic anhydrases is considered critical in the field of medicinal chemistry because carbonic anhydrases exits in several isoforms. Synthesized compounds were subjected to carbonic anhydrase –II assay. Except 5j, the other derivatives exhibited better potential than standard acetazolamide. Compound 5e was found to be potent derivative in the series with IC50 value 0.054 ± 0.001 µM. Binding analysis revealed that most potent derivative 5e binds in the active site of CA-II and single π-π stacking interaction was observed between ring structure of ligand and Phe129 having bond length 4.90 Å. Pharmacokinetics elicited that compounds obey Lipinski’s rule and show significant drug score. |
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| Keywords: | Sonogashira coupling Claisen-Schmidt reaction Silyl yne chalcone derivtaives Carbonic anhydrase-II Binding analysis Lipinsk’s rule |
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