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Research Publications (Applied Sciences)

Permanent URI for this collectionhttp://ir-dev.dut.ac.za/handle/10321/213

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Author: search.filters.author.Balogun, Fatai OladunniHas files: Yes

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    Cheminformatics identification and validation of dipeptidyl peptidase-IV modulators from Shikimate pathway-derived phenolic acids towards interventive type-2 diabetes therapy
    (MDPI AG, 2022-10) Balogun, Fatai Oladunni; Naidoo, Kaylene; Aribisala, Jamiu Olaseni; Pillay, Charlene; Sabiu, Saheed
    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 IC50 (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.
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    Identification of flavonoid C-glycosides as promising antidiabetics targeting protein tyrosine phosphatase 1B
    (Hindawi Limited, 2022-06-24) Rampadarath, Athika; Balogun, Fatai Oladunni; Pillay, Charlene; Sabiu, Saheed
    Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of the insulin signaling pathway, has gained attention as a validated druggable target in the management of type 2 diabetes mellitus (T2DM). The lack of clinically approved PTP1B inhibitors has continued to prompt research in plant-derived therapeutics possibly due to their relatively lesser toxicity profiles. Flavonoid C-glycosides are one of the plant-derived metabolites gaining increased relevance as antidiabetic agents, but their possible mechanism of action remains largely unknown. This study investigates the antidiabetic potential of flavonoid C-glycosides against PTP1B in silico and in vitro. Of the seven flavonoid C-glycosides docked against the enzyme, three compounds (apigenin, vitexin, and orientin) had the best affinity for the enzyme with a binding score of -7.3 kcal/mol each, relative to -7.4 kcal/mol for the reference standard, ursolic acid. A further probe (in terms of stability, flexibility, and compactness) of the complexes over a molecular dynamics time study of 100 ns for the three compounds suggested orientin as the most outstanding inhibitor of PTP1B owing to its overall -34.47 kcal/mol binding energy score compared to ursolic acid (-19.24 kcal/mol). This observation was in accordance with the in vitro evaluation result, where orientin had a half maximal inhibitory concentration (IC50) of 0.18 mg/ml relative to 0.13 mg/ml for the reference standard. The kinetics of inhibition of PTP1B by orientin was mixed-type with V max and K m values of 0.004 μM/s and 0.515 μM. Put together, the results suggest orientin as a potential PTP1B inhibitor and could therefore be further explored in the management T2DM as a promising therapeutic agent.