Cheminformatics Identification and Validation of Dipeptidyl Peptidase-IV Modulators from Shikimate Pathway-Derived Phenolic Acids towards Interventive Type-2 Diabetes Therapy
Recently, dipeptidyl peptidase-IV (DPP-IV) has become an effective target in the management of type-2 diabetes mellitus (T2D). The study aimed to determine the efficacy of shikimate pathway-derived phenolic acids as potential DPP-IV modulators in the management of T2D. The study explored in silico (...
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MDPI AG
2022-10-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/12/10/937 |
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| author | Fatai Oladunni Balogun Kaylene Naidoo Jamiu Olaseni Aribisala Charlene Pillay Saheed Sabiu |
| author_facet | Fatai Oladunni Balogun Kaylene Naidoo Jamiu Olaseni Aribisala Charlene Pillay Saheed Sabiu |
| author_sort | Fatai Oladunni Balogun |
| collection | DOAJ |
| description | Recently, dipeptidyl peptidase-IV (DPP-IV) has become an effective target in the management of type-2 diabetes mellitus (T2D). The study aimed to determine the efficacy of shikimate pathway-derived phenolic acids as potential DPP-IV modulators in the management of T2D. The study explored in silico (molecular docking and dynamics simulations) and in vitro (DPP-IV inhibitory and kinetics assays) approaches. Molecular docking findings revealed chlorogenic acid (CA) among the examined 22 phenolic acids with the highest negative binding energy (−9.0 kcal/mol) showing a greater affinity for DPP-IV relative to the standard, Diprotin A (−6.6 kcal/mol). The result was corroborated by MD simulation where it had a higher affinity (−27.58 kcal/mol) forming a more stable complex with DPP-IV than Diprotin A (−12.68 kcal/mol). These findings were consistent with in vitro investigation where it uncompetitively inhibited DPP-IV having a lower IC<sub>50</sub> (0.3 mg/mL) compared to Diprotin A (0.5 mg/mL). While CA showed promising results as a DPP-IV inhibitor, the findings from the study highlighted the significance of medicinal plants particularly shikimate-derived phenolic compounds as potential alternatives to synthetic drugs in the effective management of T2DM. Further studies, such as derivatisation for enhanced activity and in vivo evaluation are suggested to realize its full potential in T2D therapy. |
| first_indexed | 2024-03-09T19:48:58Z |
| format | Article |
| id | doaj.art-1dd0927cfdcd436482acce7e769ed234 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T19:48:58Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-1dd0927cfdcd436482acce7e769ed2342023-11-24T01:15:32ZengMDPI AGMetabolites2218-19892022-10-01121093710.3390/metabo12100937Cheminformatics Identification and Validation of Dipeptidyl Peptidase-IV Modulators from Shikimate Pathway-Derived Phenolic Acids towards Interventive Type-2 Diabetes TherapyFatai Oladunni Balogun0Kaylene Naidoo1Jamiu Olaseni Aribisala2Charlene Pillay3Saheed Sabiu4Department of Biotechnology and Food Science, Faculty of Applied Science, Durban University of Technology, Durban 4001, South AfricaDepartment of Biotechnology and Food Science, Faculty of Applied Science, Durban University of Technology, Durban 4001, South AfricaDepartment of Biotechnology and Food Science, Faculty of Applied Science, Durban University of Technology, Durban 4001, South AfricaDepartment of Biotechnology and Food Science, Faculty of Applied Science, Durban University of Technology, Durban 4001, South AfricaDepartment of Biotechnology and Food Science, Faculty of Applied Science, Durban University of Technology, Durban 4001, South AfricaRecently, dipeptidyl peptidase-IV (DPP-IV) has become an effective target in the management of type-2 diabetes mellitus (T2D). The study aimed to determine the efficacy of shikimate pathway-derived phenolic acids as potential DPP-IV modulators in the management of T2D. The study explored in silico (molecular docking and dynamics simulations) and in vitro (DPP-IV inhibitory and kinetics assays) approaches. Molecular docking findings revealed chlorogenic acid (CA) among the examined 22 phenolic acids with the highest negative binding energy (−9.0 kcal/mol) showing a greater affinity for DPP-IV relative to the standard, Diprotin A (−6.6 kcal/mol). The result was corroborated by MD simulation where it had a higher affinity (−27.58 kcal/mol) forming a more stable complex with DPP-IV than Diprotin A (−12.68 kcal/mol). These findings were consistent with in vitro investigation where it uncompetitively inhibited DPP-IV having a lower IC<sub>50</sub> (0.3 mg/mL) compared to Diprotin A (0.5 mg/mL). While CA showed promising results as a DPP-IV inhibitor, the findings from the study highlighted the significance of medicinal plants particularly shikimate-derived phenolic compounds as potential alternatives to synthetic drugs in the effective management of T2DM. Further studies, such as derivatisation for enhanced activity and in vivo evaluation are suggested to realize its full potential in T2D therapy.https://www.mdpi.com/2218-1989/12/10/937chlorogenic aciddiprotin Adipeptidyl peptidase IVmolecular dynamics simulationsphenolic acidstype-2 diabetes mellitus |
| spellingShingle | Fatai Oladunni Balogun Kaylene Naidoo Jamiu Olaseni Aribisala Charlene Pillay Saheed Sabiu Cheminformatics Identification and Validation of Dipeptidyl Peptidase-IV Modulators from Shikimate Pathway-Derived Phenolic Acids towards Interventive Type-2 Diabetes Therapy Metabolites chlorogenic acid diprotin A dipeptidyl peptidase IV molecular dynamics simulations phenolic acids type-2 diabetes mellitus |
| title | Cheminformatics Identification and Validation of Dipeptidyl Peptidase-IV Modulators from Shikimate Pathway-Derived Phenolic Acids towards Interventive Type-2 Diabetes Therapy |
| title_full | Cheminformatics Identification and Validation of Dipeptidyl Peptidase-IV Modulators from Shikimate Pathway-Derived Phenolic Acids towards Interventive Type-2 Diabetes Therapy |
| title_fullStr | Cheminformatics Identification and Validation of Dipeptidyl Peptidase-IV Modulators from Shikimate Pathway-Derived Phenolic Acids towards Interventive Type-2 Diabetes Therapy |
| title_full_unstemmed | Cheminformatics Identification and Validation of Dipeptidyl Peptidase-IV Modulators from Shikimate Pathway-Derived Phenolic Acids towards Interventive Type-2 Diabetes Therapy |
| title_short | Cheminformatics Identification and Validation of Dipeptidyl Peptidase-IV Modulators from Shikimate Pathway-Derived Phenolic Acids towards Interventive Type-2 Diabetes Therapy |
| title_sort | cheminformatics identification and validation of dipeptidyl peptidase iv modulators from shikimate pathway derived phenolic acids towards interventive type 2 diabetes therapy |
| topic | chlorogenic acid diprotin A dipeptidyl peptidase IV molecular dynamics simulations phenolic acids type-2 diabetes mellitus |
| url | https://www.mdpi.com/2218-1989/12/10/937 |
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