Exploring the DPP IV inhibitory potential: molecular docking and dynamic simulations of pyridine-3-carboxylic acid and pyrrolidine-2-carboxylic acid analogs DOI

Harshada H. Puranik,

Asha Thomas, Kiran Bharat Lokhande

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 21

Published: Dec. 13, 2024

Diabetes mellitus remains a global challenge, with Type 2 Mellitus (T2DM) prevalence increasing from 4% to 6.4% in the past 30 years. Presently oral hypoglycaemic agents like GLP-1 agonists, biguanides, sulphonylureas, glinides, and thiazolidinediones are employed clinical practice. Very recently, novel targets including Dipeptidyl peptidase IV (DPP IV), PPAR, GIP, FFA1, melatonin have been limelight for development of treatment strategies. The present study focuses on DPP inhibitors through computational approaches. IV, also referred as CD26 (cluster differentiation 26) or adenosine deaminase complexing protein 2, is that encoded by gene humans. This enzyme involved metabolism incretin hormones such glucagon-like peptides (GLP-1). prevent degradation GLP-1, glucose-dependent insulinotropic peptide (GIP), thereby controlling concentration glucose blood. Considering safety efficacy newer molecules were designed better binding affinity compared existing Sitagliptin, Vildagliptin-like drugs. Derivatives nicotinic acid proline studied using molecular docking dynamic simulations. Docking results demonstrated NA-13 molecule possesses potent target 6B1E (-38.1498 kcal/mol) standard Sitagliptin (-33.3187 kcal/mol). MD simulation studies showcased there fewer variations RMSD RMSF 6B1E-NA-13, 6B1E-P1, 6B1E-P7 complexes, suggesting potential management T2DM.

Language: Английский

In-silico evaluation of diffractaic acid as novel anti-diabetic inhibitor against dipeptidyl peptidase IV enzyme DOI
Miah Roney, Abdul Rashid Issahaku, Amit Dubey

et al.

In Silico Pharmacology, Journal Year: 2025, Volume and Issue: 13(1)

Published: Feb. 10, 2025

Language: Английский

Citations

1

In silico approaches to identify novel anti-diabetic type 2 agents against dipeptidyl peptidase IV from isoxazole derivatives of usnic acid DOI
Miah Roney, Md. Nazim Uddin, Suhaila Sapari

et al.

3 Biotech, Journal Year: 2025, Volume and Issue: 15(5)

Published: April 2, 2025

Language: Английский

Citations

0

Insights into the mechanism of crotamine and potential targets involved in obesity-related metabolic pathways DOI Creative Commons
David Meléndez‐Martínez, Adriana Morales-Martínez, Francisco J. Sierra-Valdez

et al.

Computers in Biology and Medicine, Journal Year: 2024, Volume and Issue: 181, P. 109049 - 109049

Published: Aug. 23, 2024

Crotamine (Ctm) is a peptide isolated from Crotalus durissus terrificus venom. This molecule has been demonstrated to diminish body weight gain and enhance browning in adipose tissue, glucose tolerance, insulin sensitivity; hence, it postulated as an anti-obesogenic peptide. However, the mechanism elicit effects yet be elucidated. Thus, we investigated possible interaction of Ctm with receptors involved obesity-related metabolic pathways through protein-protein docking molecular dynamics refinement. To test Ctm, selected retrieved 18 targets drug discovery Protein Data Bank. Then, performed dockings. The best three Ctm-target models were refined by simulations. Molecular that was able interact 13 tested. Having better score glucagon-like peptide-1 receptor (GLP-1R) (-1430.2 kcal/mol), DPP-IV (dipeptidyl peptidase-IV) (-1781.7 kcal/mol) α-glucosidase (-1232.3 kcal/mol). These dynamics. higher affinity for GLP-1R (ΔG: -41.886 ± 2.289 more stable (RMSD: 0.360 0.015 nm, Radius gyration: 2.781 0.009 nm). Moreover, number interactions mechanics energies residues suggest these mainly mediated basic-hydrophobic dyads Y1-K2, W31-R32, W33-R34. Together, all results allow elucidating behind previously described effects.

Language: Английский

Citations

1

Integrating in silico, in vitro, and in situ approaches for characterization of novel peptides from tilapia (Oreochromis niloticus) viscera hydrolysates with dipeptidyl-peptidase IV inhibitory activity DOI
Rhessa Grace Guanga Ortizo, Vishal Sharma,

Mei‐Ling Tsai

et al.

Food Bioscience, Journal Year: 2024, Volume and Issue: 63, P. 105619 - 105619

Published: Dec. 7, 2024

Language: Английский

Citations

1

Exploring the DPP IV inhibitory potential: molecular docking and dynamic simulations of pyridine-3-carboxylic acid and pyrrolidine-2-carboxylic acid analogs DOI

Harshada H. Puranik,

Asha Thomas, Kiran Bharat Lokhande

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 21

Published: Dec. 13, 2024

Diabetes mellitus remains a global challenge, with Type 2 Mellitus (T2DM) prevalence increasing from 4% to 6.4% in the past 30 years. Presently oral hypoglycaemic agents like GLP-1 agonists, biguanides, sulphonylureas, glinides, and thiazolidinediones are employed clinical practice. Very recently, novel targets including Dipeptidyl peptidase IV (DPP IV), PPAR, GIP, FFA1, melatonin have been limelight for development of treatment strategies. The present study focuses on DPP inhibitors through computational approaches. IV, also referred as CD26 (cluster differentiation 26) or adenosine deaminase complexing protein 2, is that encoded by gene humans. This enzyme involved metabolism incretin hormones such glucagon-like peptides (GLP-1). prevent degradation GLP-1, glucose-dependent insulinotropic peptide (GIP), thereby controlling concentration glucose blood. Considering safety efficacy newer molecules were designed better binding affinity compared existing Sitagliptin, Vildagliptin-like drugs. Derivatives nicotinic acid proline studied using molecular docking dynamic simulations. Docking results demonstrated NA-13 molecule possesses potent target 6B1E (-38.1498 kcal/mol) standard Sitagliptin (-33.3187 kcal/mol). MD simulation studies showcased there fewer variations RMSD RMSF 6B1E-NA-13, 6B1E-P1, 6B1E-P7 complexes, suggesting potential management T2DM.

Language: Английский

Citations

0