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Design, synthesis and molecular docking study of novel pyrrole-based α-amylase and α-glucosidase inhibitors
In an effort to design and synthesize a new class of α-glucosidase and α-amylase inhibitors, we have synthesized novel pyrrole based molecules using molecular hybridization approach. These novel analogs were synthesized by the novel methodology developed in our lab which comprises of the multi-compo...
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| Published in: | Medicinal chemistry research 2017-10, Vol.26 (10), p.2675-2691 |
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| container_title | Medicinal chemistry research |
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| creator | Jadhav, Nikhil C. Pahelkar, Akshata R. Desai, Neha V. Telvekar, Vikas N. |
| description | In an effort to design and synthesize a new class of α-glucosidase and α-amylase inhibitors, we have synthesized novel pyrrole based molecules using molecular hybridization approach. These novel analogs were synthesized by the novel methodology developed in our lab which comprises of the multi-component direct synthesis route using hypervalent iodine reagent. The compounds were characterized by infrared,
1
H nuclear magnetic resonance (NMR),
13
C NMR and Mass Spectroscopy. These compounds were screened for their α-amylase and α- glucosidase activity. They showed a varying degree of inhibition with IC
50
values ranging between 0.4 to 4.14 µmol/mL and 0.8 to 4.14 µmol/mL for α-amylase and α-glucosidase respectively. Compounds
3
,
7
,
12
, and
18
showed excellent activity as compared to standard acarbose. This has identified a new class of α-amylase and α-glucosidase inhibitor which can be further developed as antihyperglycemic agents. The molecular docking analysis was carried out to better understand of interaction between α-amylase and α-glucosidase target and inhibitors in this series. We also generated a homology model for human α-glucosidase enzyme and identified the key residues at the binding site. The outcome of the study could be used for the rational design of potent and selective α-amylase and α-glucosidase inhibitors, respectively.
Graphical abstract |
| doi_str_mv | 10.1007/s00044-017-1965-z |
| format | article |
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1
H nuclear magnetic resonance (NMR),
13
C NMR and Mass Spectroscopy. These compounds were screened for their α-amylase and α- glucosidase activity. They showed a varying degree of inhibition with IC
50
values ranging between 0.4 to 4.14 µmol/mL and 0.8 to 4.14 µmol/mL for α-amylase and α-glucosidase respectively. Compounds
3
,
7
,
12
, and
18
showed excellent activity as compared to standard acarbose. This has identified a new class of α-amylase and α-glucosidase inhibitor which can be further developed as antihyperglycemic agents. The molecular docking analysis was carried out to better understand of interaction between α-amylase and α-glucosidase target and inhibitors in this series. We also generated a homology model for human α-glucosidase enzyme and identified the key residues at the binding site. The outcome of the study could be used for the rational design of potent and selective α-amylase and α-glucosidase inhibitors, respectively.
Graphical abstract</description><identifier>ISSN: 1054-2523</identifier><identifier>EISSN: 1554-8120</identifier><identifier>DOI: 10.1007/s00044-017-1965-z</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Acarbose ; Amylases ; Binding sites ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; Chemical synthesis ; Glucosidase ; Homology ; Hybridization ; Inhibitors ; Iodine ; Mass spectroscopy ; Molecular docking ; NMR ; Nuclear magnetic resonance ; Original Research ; Pharmacology/Toxicology ; α-Amylase ; α-Glucosidase</subject><ispartof>Medicinal chemistry research, 2017-10, Vol.26 (10), p.2675-2691</ispartof><rights>Springer Science+Business Media, LLC 2017</rights><rights>Copyright Springer Science & Business Media 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c316t-e249d8e367f20df4178ac6a00092611465d4e32a75ea960d78b41269e1e665453</citedby><cites>FETCH-LOGICAL-c316t-e249d8e367f20df4178ac6a00092611465d4e32a75ea960d78b41269e1e665453</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Jadhav, Nikhil C.</creatorcontrib><creatorcontrib>Pahelkar, Akshata R.</creatorcontrib><creatorcontrib>Desai, Neha V.</creatorcontrib><creatorcontrib>Telvekar, Vikas N.</creatorcontrib><title>Design, synthesis and molecular docking study of novel pyrrole-based α-amylase and α-glucosidase inhibitors</title><title>Medicinal chemistry research</title><addtitle>Med Chem Res</addtitle><description>In an effort to design and synthesize a new class of α-glucosidase and α-amylase inhibitors, we have synthesized novel pyrrole based molecules using molecular hybridization approach. These novel analogs were synthesized by the novel methodology developed in our lab which comprises of the multi-component direct synthesis route using hypervalent iodine reagent. The compounds were characterized by infrared,
1
H nuclear magnetic resonance (NMR),
13
C NMR and Mass Spectroscopy. These compounds were screened for their α-amylase and α- glucosidase activity. They showed a varying degree of inhibition with IC
50
values ranging between 0.4 to 4.14 µmol/mL and 0.8 to 4.14 µmol/mL for α-amylase and α-glucosidase respectively. Compounds
3
,
7
,
12
, and
18
showed excellent activity as compared to standard acarbose. This has identified a new class of α-amylase and α-glucosidase inhibitor which can be further developed as antihyperglycemic agents. The molecular docking analysis was carried out to better understand of interaction between α-amylase and α-glucosidase target and inhibitors in this series. We also generated a homology model for human α-glucosidase enzyme and identified the key residues at the binding site. The outcome of the study could be used for the rational design of potent and selective α-amylase and α-glucosidase inhibitors, respectively.
Graphical abstract</description><subject>Acarbose</subject><subject>Amylases</subject><subject>Binding sites</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Chemical synthesis</subject><subject>Glucosidase</subject><subject>Homology</subject><subject>Hybridization</subject><subject>Inhibitors</subject><subject>Iodine</subject><subject>Mass spectroscopy</subject><subject>Molecular docking</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Original Research</subject><subject>Pharmacology/Toxicology</subject><subject>α-Amylase</subject><subject>α-Glucosidase</subject><issn>1054-2523</issn><issn>1554-8120</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNp1kE1OwzAQhS0EEqVwAHaW2GKwHf_ES1R-pUpsYG25sZOmJHGxE6T0VlyEM-ESFmxYzZvRezOaD4Bzgq8IxvI6YowZQ5hIRJTgaHcAZoRzhnJC8WHSOGnKaXYMTmLcYJxJzPgMtLcu1lV3CePY9eukIzSdha1vXDE0JkDri7e6q2DsBztCX8LOf7gGbscQkgetTHQWfn0i045N0j_p1FbNUPhY2_2o7tb1qu59iKfgqDRNdGe_dQ5e7-9eFo9o-fzwtLhZoiIjokeOMmVzlwlZUmxLRmRuCmHSi4oKQpjglrmMGsmdUQJbma8YoUI54oTgjGdzcDHt3Qb_PrjY640fQpdOaqKYxErleZ5cZHIVwccYXKm3oW5NGDXBek9VT1R1oqr3VPUuZeiUicnbVS782fxv6BtWfnyf</recordid><startdate>20171001</startdate><enddate>20171001</enddate><creator>Jadhav, Nikhil C.</creator><creator>Pahelkar, Akshata R.</creator><creator>Desai, Neha V.</creator><creator>Telvekar, Vikas N.</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope></search><sort><creationdate>20171001</creationdate><title>Design, synthesis and molecular docking study of novel pyrrole-based α-amylase and α-glucosidase inhibitors</title><author>Jadhav, Nikhil C. ; Pahelkar, Akshata R. ; Desai, Neha V. ; Telvekar, Vikas N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c316t-e249d8e367f20df4178ac6a00092611465d4e32a75ea960d78b41269e1e665453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acarbose</topic><topic>Amylases</topic><topic>Binding sites</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Biology</topic><topic>Chemical synthesis</topic><topic>Glucosidase</topic><topic>Homology</topic><topic>Hybridization</topic><topic>Inhibitors</topic><topic>Iodine</topic><topic>Mass spectroscopy</topic><topic>Molecular docking</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Original Research</topic><topic>Pharmacology/Toxicology</topic><topic>α-Amylase</topic><topic>α-Glucosidase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jadhav, Nikhil C.</creatorcontrib><creatorcontrib>Pahelkar, Akshata R.</creatorcontrib><creatorcontrib>Desai, Neha V.</creatorcontrib><creatorcontrib>Telvekar, Vikas N.</creatorcontrib><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Medicinal chemistry research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jadhav, Nikhil C.</au><au>Pahelkar, Akshata R.</au><au>Desai, Neha V.</au><au>Telvekar, Vikas N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design, synthesis and molecular docking study of novel pyrrole-based α-amylase and α-glucosidase inhibitors</atitle><jtitle>Medicinal chemistry research</jtitle><stitle>Med Chem Res</stitle><date>2017-10-01</date><risdate>2017</risdate><volume>26</volume><issue>10</issue><spage>2675</spage><epage>2691</epage><pages>2675-2691</pages><issn>1054-2523</issn><eissn>1554-8120</eissn><abstract>In an effort to design and synthesize a new class of α-glucosidase and α-amylase inhibitors, we have synthesized novel pyrrole based molecules using molecular hybridization approach. These novel analogs were synthesized by the novel methodology developed in our lab which comprises of the multi-component direct synthesis route using hypervalent iodine reagent. The compounds were characterized by infrared,
1
H nuclear magnetic resonance (NMR),
13
C NMR and Mass Spectroscopy. These compounds were screened for their α-amylase and α- glucosidase activity. They showed a varying degree of inhibition with IC
50
values ranging between 0.4 to 4.14 µmol/mL and 0.8 to 4.14 µmol/mL for α-amylase and α-glucosidase respectively. Compounds
3
,
7
,
12
, and
18
showed excellent activity as compared to standard acarbose. This has identified a new class of α-amylase and α-glucosidase inhibitor which can be further developed as antihyperglycemic agents. The molecular docking analysis was carried out to better understand of interaction between α-amylase and α-glucosidase target and inhibitors in this series. We also generated a homology model for human α-glucosidase enzyme and identified the key residues at the binding site. The outcome of the study could be used for the rational design of potent and selective α-amylase and α-glucosidase inhibitors, respectively.
Graphical abstract</abstract><cop>New York</cop><pub>Springer US</pub><doi>10.1007/s00044-017-1965-z</doi><tpages>17</tpages></addata></record> |
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| subjects | Acarbose Amylases Binding sites Biochemistry Biomedical and Life Sciences Biomedicine Cell Biology Chemical synthesis Glucosidase Homology Hybridization Inhibitors Iodine Mass spectroscopy Molecular docking NMR Nuclear magnetic resonance Original Research Pharmacology/Toxicology α-Amylase α-Glucosidase |
| title | Design, synthesis and molecular docking study of novel pyrrole-based α-amylase and α-glucosidase inhibitors |
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