https://commons.ru.ac.za/vital/access/manager/Index en-us 5 https://commons.ru.ac.za/vital/access/manager/Repository/vital:28690 Wed 19 Apr 2023 13:28:11 SAST ]]> https://commons.ru.ac.za/vital/access/manager/Repository/vital:56841 Tue 25 Oct 2022 14:23:47 SAST ]]> https://commons.ru.ac.za/vital/access/manager/Repository/vital:49968 100% inhibition in concentrations ≥ 30 μg/mL and TZDD1, 2 and 4 exhibited ≥ 50% inhibition activity in all the concentrations (10, 20, 30, 40 and 50 μg/mL) in the α-amylase inhibition assay. Similarly, in the α-glucosidase inhibition assay, all the four derivatives exhibited a concentration dependent activity with TZDD3 showing the most activity. All the four derivatives exhibited ≥ 30% inhibition in the aldose reductase inhibition assay except TZDD1 at 10 μg/mL. TZDD4 exhibited a concentration dependent inhibition activity in the protein tyrosine phosphatase-1B inhibition assay. Interestingly, TZDD3 showed a decreasing inhibition activity as its concentration increased from 10 μg/mL through to 50 μg/mL. In the dipeptidyl peptidase–4 inhibition assay, TZDD2 and TZDD4 exhibited ≥ 20% inhibition activity across all the concentrations and in the acetylcholinesterase assay, TZDD1, 3 and 4 exhibited ≥ 25% across all the concentrations. Interestingly, in the matrix metalloproteinase-1 inhibition assay, some of these derivatives exhibited partial activation activity and partial inhibition with TZDD1 showing activation in concentrations 10 and 20 μg/mL and inhibition in concentrations 30, 40 and 50 μg/mL. TZDD4 showed activation in all the concentrations. In the β-amyloid aggregation assay, all the four derivatives showed inhibition activity ≥ 10% except TZDD1 at 50 μg/mL. Conclusions Diabetes mellitus and Alzheimer’s disease are a type of pathology of global concern, and several researchers worldwide have strived to search for novel therapeutic treatments and prevention for diabetes as well as Alzheimer’s disease. Recent studies provide a direct link v between diabetes mellitus and Alzheimer’s disease, and the need to find novel drugs that can mitigate these two is of increasing interest. In our search for antidiabetic and anti-Alzheimer’s activity, TZD derivatives (TZDD1, TZDD2, TZDD3 and TZDD4) exhibited good antioxidant activity, anti-hyperglycaemic activity and a relatively promising anti-Alzheimer’s activity. This was observed from the in vitro evaluation performed which included α – amylase, α – glucosidase, aldose reductase, PTP1B, DPP4, amyloid β aggregation, and AChE inhibition assays. Furthermore, docking of the derivatives against PPARγ predicted a similar molecular interaction to that of thiazolidinediones using Rosiglitazone as the standard drug. Furthermore, in silico ADME profiling predicted the derivatives to have moderate to good solubility in the GI (good GI bioavailability), and also exhibited excellent drug likeness. However, they are predicted not permeate the BBB. Further in silico studies and in vivo should be conducted to establish toxicities, as well as drug delivery to the brain for effective therapeutic effect against Alzheimer’s disease.]]> Tue 21 Nov 2023 19:57:12 SAST ]]> https://commons.ru.ac.za/vital/access/manager/Repository/vital:68596 Tue 07 May 2024 14:52:04 SAST ]]> https://commons.ru.ac.za/vital/access/manager/Repository/vital:27456 Thu 13 Apr 2023 09:16:21 SAST ]]> https://commons.ru.ac.za/vital/access/manager/Repository/vital:28428 Thu 09 Mar 2023 11:57:44 SAST ]]> https://commons.ru.ac.za/vital/access/manager/Repository/vital:70632 Mon 13 May 2024 15:48:08 SAST ]]> https://commons.ru.ac.za/vital/access/manager/Repository/vital:41017 Fri 31 Mar 2023 12:10:54 SAST ]]>