Identification of promising multi-targeting inhibitors of obesity from Vernonia amygdalina through computational analysis

Ogunyemi, Oludare M.; Gyebi, Gideon A.; Ibrahim, Ibrahim M.; Esan, Adewale M.; Olaiya, Charles O.; Soliman, Mohameed M; Batiha, Gaber El‐Saber

doi:10.1007/s11030-022-10397-6

Cited by 25 publications

(18 citation statements)

References 67 publications

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“…Alpha-amylase is widely exploited as a drug target for preventing postprandial hyperglycemia in diabetes and other metabolic diseases ( Borah et al, 2019 ; Ogunyemi et al, 2022 ). Pregnane-rich plant extracts are known to possess strong alpha-amylase inhibitory potential and thereby serve as important bioresources for preventive nutraceuticals and potent antidiabetic agents as discussed earlier.…”

Section: Discussionmentioning

confidence: 99%

“…A well-known therapeutic approach for the prevention and management of diabetes is decreasing diet-dependent blood glucose rise. This can be achieved by blunting dietary carbohydrate digestion in the gut through inhibition of digestive enzymes including alpha-amylase and alpha-glucosidase ( Kim et al, 2005 ; Ogunyemi et al, 2022 ). The enzyme alpha-amylase (1,4-α-D-glucan glucanohydrolase, EC 3.2.1.1) is a key therapeutic target that has been exploited for developing several synthetic drugs such as acarbose, voglibose, and miglitol ( Alqahtani et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…Many herbal extracts derived from herbs, spices, and medicinal plants with acknowledged and scientifically proven antidiabetic properties serve to complement current therapies in developing countries ( Poovitha and Parani, 2016 ; Ogunyemi et al, 2022 ). The ethnopharmacological use of such herbs is increasingly gaining importance as medicines due to accumulating scientific evidence.…”

Section: Introductionmentioning

confidence: 99%

“…The enzyme alpha-amylase (1,4-α-D-glucan glucanohydrolase, EC 3.2.1.1) is a key therapeutic target that has been exploited for developing several synthetic drugs such as acarbose, voglibose, and miglitol ( Alqahtani et al, 2019 ). Several amylase inhibitors have also been identified from natural sources ( Ogunyemi et al, 2020 ; Lankatillake et al, 2021 ; Ogunyemi et al, 2022 ). The alpha-amylase mainly occurring in the saliva and pancreas ( Stiefel and Keller, 1973 ) helps to start the chemical process of carbohydrate breakdown by hydrolyzing the glycosidic bonds in starch and related substrate polysaccharides, transforming them into oligosaccharides and simple absorbable sugars.…”

Section: Introductionmentioning

confidence: 99%

“…The ethnopharmacological use of such herbs is increasingly gaining importance as medicines due to accumulating scientific evidence. They are also considered important vegetal resources for alpha-amylase inhibitors, preventive nutraceuticals, and antidiabetic drugs and may be exploited as an oral policy for impeding postprandial blood glucose rise in diabetes and metabolic syndrome ( Dhital et al, 2013 ; Nyambe-Silavwe et al, 2015 ; Ogunyemi et al, 2022 ). Such antidiabetic plants and their activity against alpha-amylase were recently reviewed extensively by Kaur et al (2021) .…”

Section: Introductionmentioning

confidence: 99%

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Inhibition mechanism of alpha-amylase, a diabetes target, by a steroidal pregnane and pregnane glycosides derived from Gongronema latifolium Benth

Ogunyemi

Gyebi

Saheed

et al. 2022

Front. Mol. Biosci.

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Alpha-amylase is widely exploited as a drug target for preventing postprandial hyperglycemia in diabetes and other metabolic diseases. Inhibition of this enzyme by plant-derived pregnanes is not fully understood. Herein, we used in vitro, in silico, and in vivo studies to provide further insights into the alpha-amylase inhibitory potential of selected pregnane-rich chromatographic fractions and four steroidal pregnane phytochemicals (SPPs), viz: marsectohexol (P1), 3-O-[6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→14)-β-D-oleandropyranosyl]-11,12-di-O-tigloyl-17β-marsdenin (P2), 3-O-[6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl]-17β-marsdenin (P3), and 3-O-[6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-canaropyranosyl]-17β-marsdenin (P4) derived from Gongronema latifolium Benth. The results revealed that the SPPs source pregnane-rich chromatographic fractions and the SPPs (P1–P4) exhibited inhibitory potential against porcine pancreatic alpha-amylase in vitro. Compounds P1 and P2 with IC50 values 10.01 and 12.10 µM, respectively, showed greater inhibitory potential than the reference acarbose (IC50 = 13.47 µM). Molecular docking analysis suggests that the SPPs had a strong binding affinity to porcine pancreatic alpha-amylase (PPA), human pancreatic alpha-amylase (HPA), and human salivary alpha-amylase (HSA), interacting with the key active site residues through an array of hydrophobic interactions and hydrogen bonds. The strong interactions of the SPPs with Glu233 and Asp300 residues may disrupt their roles in the acid-base catalytic mechanism and proper orientation of the polymeric substrates, respectively. The interactions with human pancreatic amylase were maintained in a dynamic environment as indicated by the root mean square deviation, radius of gyration, surface accessible surface area, and number of hydrogen bonds computed from the trajectories obtained from a 100-ns molecular dynamics simulation. Key loop regions of HPA that contribute to substrate binding exhibited flexibility and interaction potential toward the compounds as indicated by the root mean square fluctuation. Furthermore, P1 significantly reduced blood glucose levels and area under the curve in albino rats which were orally challenged with starch. Therefore, Gongronema latifolium and its constituent SPPs may be exploited as inhibitors of pancreatic alpha-amylase as an oral policy for impeding postprandial blood glucose rise.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibition mechanism of alpha-amylase, a diabetes target, by a steroidal pregnane and pregnane glycosides derived from Gongronema latifolium Benth

Ogunyemi

Gyebi

Saheed

et al. 2022

Front. Mol. Biosci.

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Synthesis, photophysical properties, anticancer evaluation, and molecular docking studies of new pyrimidine linked 4‐arylidene‐thiazolidin‐4‐ones as potent anticancer agents

Jame

2024

Luminescence

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The reaction of 4‐(chloroacetamido)pyrimidine (1) with ammonium thiocyanate gave 2‐(pyrimidin‐4‐ylimino)thiazolidin‐4‐one (2), which, when condensed with four substituted benzaldehyde analogues, gave the consequent 5‐arylidine‐2‐(pyrimidin‐4‐ylimino)thiazolidin‐4‐ones 3a–d. In addition, the absorbance and fluorescence behaviours of pyrimidinylimino‐thiazolidin‐4‐one hybrids 3a–d in various organic solvents were investigated. The emphasis was on studying UV absorption capacities and the effect of various structural components on photophysical qualities such as the 5‐arylidene‐2‐(pyrimidin‐4‐ylimino)thiazolidin‐4‐ones and N,N‐dimethylamino tail. The cytotoxic effect of four pyrimidinylimino‐thiazolidin‐4‐one hybrids 3a–d on tumour cell lines (HepG2, HCT‐116, PC3, MCF‐7) and a normal cell line (WI38) is investigated in this work. The cytotoxicity was measured by comparing the half‐maximal inhibitory concentration (IC50) to the reference medication, 5‐fluorouracil. The findings indicate that these hybrid compounds had varying cytotoxic effects on the cell lines examined; hybrids 3b and 3c demonstrated significant anticancer activity against MCF‐7 with IC50 values of 7.53 ± 0.43 and 9.17 ± 0.31 μM, respectively. The inhibitory efficacy of various synthesized hybrids on the epidermal growth factor receptor (EGFR) kinase was investigated. EGFR is a crucial target in cancer treatment because inhibiting it may reduce tumour development and proliferation. The IC50 value was used to calculate the inhibitory activity, which is the concentration of inhibitor necessary to induce half‐maximal inhibition of EGFR kinase activity. In addition, the predicted ADME results show that pyrimidinylimino‐thiazolidin‐4‐one hybrids have good pharmacokinetic properties; hybrid 3d is more lipophilic than the other compounds. It has a medium molecular weight, a small number of hydrogen bond acceptors and donors, and a large number of aromatic heavy atoms. Moreover, molecular docking simulations revealed precise information on the interactions of pyrimidinylimino‐thiazolidin‐4‐one hybrids 3a–d and 5‐Fu with their respective protein targets. These interactions point to possible pathways for their biological activities and call for more testing to establish their effectiveness as bioactive molecules or therapeutic candidates.

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Computational Methods to Study Herb-Drug Interactions

Hemaiswarya

Prabhakar

Doble

2022

Herb-Drug Combinations

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Identification of promising multi-targeting inhibitors of obesity from Vernonia amygdalina through computational analysis

Cited by 25 publications

References 67 publications

Inhibition mechanism of alpha-amylase, a diabetes target, by a steroidal pregnane and pregnane glycosides derived from Gongronema latifolium Benth

Inhibition mechanism of alpha-amylase, a diabetes target, by a steroidal pregnane and pregnane glycosides derived from Gongronema latifolium Benth

Synthesis, photophysical properties, anticancer evaluation, and molecular docking studies of new pyrimidine linked 4‐arylidene‐thiazolidin‐4‐ones as potent anticancer agents

Computational Methods to Study Herb-Drug Interactions

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