Reema Abu Khalaf1, Dima Sabbah1, Eveen Al-Shalabi1, Iyad Al-Sheikh1, Ghadeer Albadawi1, Ghassan Abu Sheikha1.
Abstract
BACKGROUND: Diabetes mellitus is a major worldwide health concern that has several serious complications including retinopathy, neuropathy, nephropathy and macrovascular diseases.
OBJECTIVE: Dipeptidyl peptidase-IV (DPP-IV) inhibitors, gliptins, are a new class of antidiabetic agents that potentiate the action of incretins in decreasing the blood glucose levels.
METHODS: In the present study, synthesis and characterization of a series of ten N4-sulfonamido-acrylic and phthalamic acid methyl esters (3a-e and 5a-e) were achieved.
RESULTS: In vitro anti-DPP-IV activity of the synthesized compounds was evaluated, where compound 3b demonstrated the best activity with a % inhibition of 41.7 at 10 µM concentration and an IC50 of 23.9 µM. Moreover, Glide docking experiments revealed that our targeted compounds accommodate the binding site of DPP-IV and tend to form H-bonding with the backbones of R125, E206, S209, D545, K554, W629, Y631, and G632.
CONCLUSION: Modeling findings recommend the attachment of bulky hydrophobic group on the ester side of the structure in addition to harboring extra aromatic rings that might be beneficial for better binding interaction and biological activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
BACKGROUND: Diabetes mellitus is a major worldwide health concern that has several serious complications including retinopathy, neuropathy, nephropathy and macrovascular diseases.
OBJECTIVE: Dipeptidyl peptidase-IV (DPP-IV) inhibitors, gliptins, are a new class of antidiabetic agents that potentiate the action of incretins in decreasing the blood glucose levels.
METHODS: In the present study, synthesis and characterization of a series of ten N4-sulfonamido-acrylic and phthalamic acid methyl esters (3a-e and 5a-e) were achieved.
RESULTS: In vitro anti-DPP-IV activity of the synthesized compounds was evaluated, where compound 3b demonstrated the best activity with a % inhibition of 41.7 at 10 µM concentration and an IC50 of 23.9 µM. Moreover, Glide docking experiments revealed that our targeted compounds accommodate the binding site of DPP-IV and tend to form H-bonding with the backbones of R125, E206, S209, D545, K554, W629, Y631, and G632.
CONCLUSION: Modeling findings recommend the attachment of bulky hydrophobic group on the ester side of the structure in addition to harboring extra aromatic rings that might be beneficial for better binding interaction and biological activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Entities:
Keywords:
Acrylic acid; DPP-IV inhibitors; diabetes mellitus; glide docking; phthalamic acid; sulfamoyl acid ester.
Mesh：
Substances：
Year: 2018
PMID： 29521244 DOI： 10.2174/1573409914666180308164013
Source DB: PubMed Journal: Curr Comput Aided Drug Des ISSN： 1573-4099 Impact factor: 1.606