The first target specific,highly diastereoselective synthesis,design and characterization of pyranoquinolinyl acrylic acid diastereomers as potential α-glucosidase inhibitors |
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| Institution: | 1. PG& Research Department of Chemistry, Arignar Anna Govt Arts College, Cheyyar, Tamil Nadu, India;2. Department of Chemistry, National Taiwan University, Roosevelt Road, Taipei 10617, Taiwan;1. Department of Electrical and Computer Engineering, National University of Singapore, Singapore;2. Department of Electrical Engineering, University of Notre Dame, USA;1. Department of Chemistry, Kinnaird College for Women, Lahore 54000, Pakistan;2. Department of Biotechnology, Kinnaird College for Women, Lahore 54000, Pakistan;3. Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan;4. Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, Lahore 54600, Pakistan;5. Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan;1. Department of Chemistry, Kinnaird College for Women, Lahore 54000, Pakistan;2. Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan;3. Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan;4. Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, Lahore 54600, Pakistan;5. Department of Biotechnology, Kinnaird College for Women, Lahore 54000, Pakistan;1. Department of Pharmacology and Bioinformatics, Volgograd State Medical University, Pavshikh Bortsov Sq. 1, Volgograd 400131, Russia;2. Scientific Center for Innovative Drugs, Volgograd State Medical University, Novorossiyskaya St. 39, Volgograd 400087, Russia;3. Department of Organic Chemistry, Samara State Technical University, Molodogvardeiskaya St. 244, Samara 443100, Russia;1. Ufa Institute of Chemistry UFRS RAS, 71 pr. Oktyabrya, Ufa 450054, Russian Federation;2. Bashkir State University, 32 Validy Str., Ufa 450076, Russian Federation;3. Institute of Chemistry, Vietnamese Academy of Science and Technology, 18 Hoang Quoc Viet Str., Cau Giay Dist., Hanoi, Viet Nam;4. Scientific Center for Innovative Drugs, Volgograd State Medical University, Novorossiyskaya st. 39, Volgograd 400087, Russian Federation |
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| Abstract: | In the present investigation we report the first target specific, highly diastereoselective synthesis of new class of pyranoquinolinyl/furoquinolinyl-acrylic acid diastereomers and evaluation of their invitro α-glucosidase inhibitory activity. All the products were thoroughly characterized by 1H NMR, 13C NMR, FT-IR, Mass spectral and CHN analysis. A highly diastereoselective target specific route of synthesis for the biologically active diastereomers were developed by usingchiral catalyst Europium tris3-heptafluoropropylhydroxyl methylene]-(−)-camphorate (A) or Europiumtris3-(trifluoromethyl)hydroxylmethylene]-(+)-camphorate (B). It was found that among a set of 4 diastereomeric products obtained, exodiasteromers of pyranoquinolinyl acrylic acid adducts exhibited relatively high α-glucosidase inhibitory activity. The newly synthesized compounds exhibited IC50 values in the range of (0.40 ± 0.02–30.3 ± 0.84 μM) as compared to standard acarbose (IC50 = 0.65 ± 0.02 μM). It was found that compounds 11a, 11c, 11d and 12d were found to be more active than standard acarbose. It was also found that unsubstituted compound (11a) or compounds with chlorine or methoxy substituent (11c, 11d, 12d) showed potential α-glucosidase inhibitory activity. However a reversal in activity was observed with Nitro substituent (11b, 13b) wherein the endodiastereomers were found to be more active than exodiastereomers. Molecular docking studies were used for design of the compound and understand the mode of binding between the compound and target enzyme. A plausible mechanism for the diastereoselective synthesis was also proposed. |
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| Keywords: | Target specific synthesis α-glucosidase inhibitors Antidiabetic Diastereoselective synthesis Pyranoquinolinyl acrylic acid diastereomers |
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