Gajjar_2021_Curr.Drug.Discov.Technol__

Reference

Title : Structure-Based De Novo Design and Docking Studies of 5(S)-Methyl-L-Proline Containing Peptidomimetic Compounds as Dipeptidyl Peptidase-4 Inhibitors - Gajjar_2021_Curr.Drug.Discov.Technol__
Author(s) : Gajjar AK , Pathak CD
Ref : Curr Drug Discov Technol , : , 2021
Abstract :

BACKGROUND: Diabetes affects millions of people worldwide, with predicted numbers of about 700 million adults affected by 2045. Among the several anti-diabetic drug therapies available in the market, Dipeptidyl Peptidase-4 (DPP-4) inhibitors have emerged as a promising therapeutic approach with scope for exploration in the segment of peptidomimetics. OBJECTIVE: Series of proline-containing peptidomimetic compounds were designed and investigated for their drug-likeness through Lipinski's rule of five, lead-likeness through the rule of three, predictive pharmacokinetic studies (absorption, distribution, metabolism, and excretion), and toxicity properties through in-silico approaches. The designed compounds were evaluated for their interactions with binding sites of the enzyme DPP-4 using an extra precision docking approach. METHODS: Proline-containing peptidomimetic compounds were designed rationally. Drug-likeness and lead-likeness properties were calculated using Schrodinger Maestro v11.2 software. ADME and toxicity properties were predicted using PreADMET version 2.0. Docking study was performed using Schrodinger Maestro v11.2 software, and ligands for the study were designed using MarvinSketch software. RESULTS: 5(S)-methyl-L-proline containing 17 ligands were designed. All of them were found to obey Lipinski's rule of five. Compounds were found to have good ADME profile and low toxicity predictions. CONCLUSION: Four compounds were found to have good interactions with DPP-4 binding sites and hence created the scope to develop a DPP-4 inhibitors containing 5(S)-methyl-L-proline moiety.

PubMedSearch : Gajjar_2021_Curr.Drug.Discov.Technol__
PubMedID: 34939544

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Citations formats

Gajjar AK, Pathak CD (2021)
Structure-Based De Novo Design and Docking Studies of 5(S)-Methyl-L-Proline Containing Peptidomimetic Compounds as Dipeptidyl Peptidase-4 Inhibitors
Curr Drug Discov Technol :

Gajjar AK, Pathak CD (2021)
Curr Drug Discov Technol :