Evaluation of selected carotenoids of Lycopersicon esculentum variants as therapeutic targets for 'Alzheimer's disease: an in silico approach

Olalekan Olanrewaju Bakare; Adewale Oluwaseun Fadaka; Musa Oyebowale Akanbi; Kolajo Adedamola Akinyede; Ashwil Klein; Marshall Keyster

doi:10.1186/s12860-021-00386-2

Evaluation of selected carotenoids of Lycopersicon esculentum variants as therapeutic targets for 'Alzheimer's disease: an in silico approach

BMC Mol Cell Biol. 2021 Oct 1;22(1):49. doi: 10.1186/s12860-021-00386-2.

Authors

Olalekan Olanrewaju Bakare^{1

2}, Adewale Oluwaseun Fadaka^{3

4}, Musa Oyebowale Akanbi⁵, Kolajo Adedamola Akinyede⁶, Ashwil Klein⁷, Marshall Keyster⁵

Affiliations

¹ Bioinformatics research group, Department of Biotechnology, Faculty of Natural Sciences, University of the Western Cape, Private Bag X17, Bellville, Cape Town, 7535, South Africa. lekanbakare77@gmail.com.
² Environmental Biotechnology Laboratory (EBL), Department of Biotechnology, Faculty of Natural Sciences, University of the Western Cape, Cape Town, South Africa. lekanbakare77@gmail.com.
³ Bioinformatics research group, Department of Biotechnology, Faculty of Natural Sciences, University of the Western Cape, Private Bag X17, Bellville, Cape Town, 7535, South Africa.
⁴ Department of Science and Technology/Mintek Nanotechnology Innovation Centre, Biolabels Node, Department of Biotechnology, Faculty of Natural Sciences, University of the Western Cape, Private Bag X17, Bellville, 7535, South Africa.
⁵ Environmental Biotechnology Laboratory (EBL), Department of Biotechnology, Faculty of Natural Sciences, University of the Western Cape, Cape Town, South Africa.
⁶ Department of Medical Bioscience, University of the Western Cape, Bellville, Cape Town, 7535, South Africa.
⁷ Plant Omics group, Department of Biotechnology, Faculty of Natural Sciences, University of the Western Cape, Private Bag X17, Bellville, Cape Town, 7535, South Africa.

Abstract

The seriousness and menace of the worldwide weight of 'Alzheimer's disease have been related to a few factors, which incorporate antioxidant system depletion, mutation of proteins, and high expression of cholinesterases due to aging, environmental influence, diet, infectious agents, and hormonal imbalance. Overexpression of cholinesterases has been emphatically connected to 'Alzheimer's disease because of the unreasonable hydrolysis of acetylcholine and butyrylcholine. Certain plant phytochemicals, for example, beta-carotenoids, lutein, neoxanthin, and viola-xanthine from Lycopersicon esculentum Mill. Var. esculentum (ESC) and Lycopersicon esculentum Mill. Var. cerasiforme (CER) has been utilized altogether as a therapeutic candidate for the treatment of 'Alzheimer's disease. Therefore, this research sought to investigate the drug-likeness of the individual carotenoids as detailed for cholinesterase inhibition in the treatment of 'Alzheimer's disease. Four potential cholinesterase inhibitors from ESC and CER were retrieved from the PubChem database. Investigation of their drug-likeness, toxicity prediction, molecular docking, and dynamic simulations were carried out using Molinspiration, PreADMET V.2.0, Patchdock server, and Schrodinger Maestro software respectively. Neoxanthin was ranked the safest with a greater tendency to inhibit the cholinesterases with high binding affinity. In addition, its stability after simulation in a mimicked biological environment suggests its relevance as a potential drug candidate for the treatment of 'Alzheimer's disease through the inhibition of cholinesterases.

Keywords: Carotenoids; Drug-likeness; In silico; Inhibitors; Ligands; Phytochemicals; Therapeutic; Toxicity; ‘Alzheimer’s.

MeSH terms

Alzheimer Disease* / drug therapy
Carotenoids / therapeutic use
Cholinesterase Inhibitors / therapeutic use
Humans
Molecular Docking Simulation
Solanum lycopersicum*

Substances

Cholinesterase Inhibitors
Carotenoids