Version 1
: Received: 4 October 2023 / Approved: 4 October 2023 / Online: 9 October 2023 (09:36:05 CEST)
How to cite:
Nema, P.; Agarwal, S.; Kori, S.K.; Kumar, A.; Kashaw, V.; Soni, V.; Iyer, A.K.; Kashaw, S.K. Exhaustive Computational Studies on Pyrimidine Derivatives as GPR119 agonist for the Development of Compounds against NIDDM. Preprints2023, 2023100396. https://doi.org/10.20944/preprints202310.0396.v1
Nema, P.; Agarwal, S.; Kori, S.K.; Kumar, A.; Kashaw, V.; Soni, V.; Iyer, A.K.; Kashaw, S.K. Exhaustive Computational Studies on Pyrimidine Derivatives as GPR119 agonist for the Development of Compounds against NIDDM. Preprints 2023, 2023100396. https://doi.org/10.20944/preprints202310.0396.v1
Nema, P.; Agarwal, S.; Kori, S.K.; Kumar, A.; Kashaw, V.; Soni, V.; Iyer, A.K.; Kashaw, S.K. Exhaustive Computational Studies on Pyrimidine Derivatives as GPR119 agonist for the Development of Compounds against NIDDM. Preprints2023, 2023100396. https://doi.org/10.20944/preprints202310.0396.v1
APA Style
Nema, P., Agarwal, S., Kori, S.K., Kumar, A., Kashaw, V., Soni, V., Iyer, A.K., & Kashaw, S.K. (2023). Exhaustive Computational Studies on Pyrimidine Derivatives as GPR119 agonist for the Development of Compounds against NIDDM. Preprints. https://doi.org/10.20944/preprints202310.0396.v1
Chicago/Turabian Style
Nema, P., Arun K Iyer and Sushil Kumar Kashaw. 2023 "Exhaustive Computational Studies on Pyrimidine Derivatives as GPR119 agonist for the Development of Compounds against NIDDM" Preprints. https://doi.org/10.20944/preprints202310.0396.v1
Abstract
(1) Background: Type-2 Diabetes (T2DM) is a long-term medical disorder characterized by Insulin deficiency and high blood glucose levels. Among other medication to cure T2DM, the review of the literature found that various Pyrimidine derivative act as an agonist for G-protein-coupled receptor 119 (GPR119) was proposed to control blood glucose levels by enhancing the function of pancreatic beta-cells and its mechanism of action with fewer adverse effects.; (2) Methods: In the present research work, in-silico investigations were carried out to investigate the potential of Pyrimidine analogue as an agonists to the protein target GPR119 receptor. We performed exhaustive molecular modelling and protein modelling methodologies such as homology mod-elling, molecular docking along with various drug designing tools such as 3D-QSAR and pharmacophore mapping to ascertain the design of better GPR119 agonists.; (3) Results: On the basis of in-depth computa-tional studies, we designed new pyrimidine moiety and analyzed them for GPR-119 receptor agonist and fur-ther explored the ADME properties. Designed compounds found to exhibit better predicted activities as com-pared to reference compound; (4) Conclusions: The current research on pyrimidine derivatives, using molec-ular docking, 3D-QSAR and Pharmacophore mapping demonstrated that the obtained computational model has significant properties and the designed molecules and Dataset from this model, produced antidiabetic compound against the target GPR119 i.e., compound 1S, 1Z and 1D with the docking score of −11.696, -9.314 and -8.721 respectively. The pharmacokinetics and drug-likeness studies revealed that these compounds may be the future candidate for the treatment of diabetes acting via GPR119 agonist mechanism.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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