<i>Spondias mombim</i>L. (Anacardiaceae): Chemical fingerprints, inhibitory activities, and molecular docking on key enzymes relevant to erectile dysfunction and Alzheimer’s diseases

Ojo, Oluwafemi Adeleke; Afon, Adeola Agnes; Ojo, Adebola Busola; Ajiboye, Basiru Olaitan; Okesola, Mary Abiola; Aruleba, Raphael Taiwo; Adekiya, Tayo Alex; Oyinloye, Babatunji Emmanuel

doi:10.1111/jfbc.12772

Cited by 19 publications

(9 citation statements)

References 71 publications

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“…Consequently, interference of any kind with any of these enzymes leads to a breakdown of the drug molecule [49,74]. Additionally, when a compound is discovered to be a substrate for at least one type of CYP450 enzyme, it means the compound is anticipated to be easily and seriously metabolized by the respective CYP450 enzyme or enzymes [19]. Another influencer of the pharmacodynamics, circulation and excretion of the drug is the ability of a drug to bind to plasma proteins which also signifies a pharmacological index.…”

Section: Discussionmentioning

confidence: 99%

“…Alzheimer's disease (AD) is exemplified by cognitive decline and several other intellectual damage symptoms. It is presently the most challenging advanced neurodegenerative diseases to manage [17][18][19]. Over the years, numerous hypotheses on the pathogenesis of AD have been suggested, including the amyloid cascade, tau protein, oxidative and cholinergic hypothesis [20].…”

Section: Introductionmentioning

confidence: 99%

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Deciphering the Interactions of Bioactive Compounds in Selected Traditional Medicinal Plants against Alzheimer’s Diseases via Pharmacophore Modeling, Auto-QSAR, and Molecular Docking Approaches

Ojo

Okolie

et al. 2021

Molecules

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Neurodegenerative diseases, for example Alzheimer’s, are perceived as driven by hereditary, cellular, and multifaceted biochemical actions. Numerous plant products, for example flavonoids, are documented in studies for having the ability to pass the blood-brain barrier and moderate the development of such illnesses. Computer-aided drug design (CADD) has achieved importance in the drug discovery world; innovative developments in the aspects of structure identification and characterization, bio-computational science, and molecular biology have added to the preparation of new medications towards these ailments. In this study we evaluated nine flavonoid compounds identified from three medicinal plants, namely T. diversifolia, B. sapida, and I. gabonensis for their inhibitory role on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoamine oxidase (MAO) activity, using pharmacophore modeling, auto-QSAR prediction, and molecular studies, in comparison with standard drugs. The results indicated that the pharmacophore models produced from structures of AChE, BChE and MAO could identify the active compounds, with a recuperation rate of the actives found near 100% in the complete ranked decoy database. Moreso, the robustness of the virtual screening method was accessed by well-established methods including enrichment factor (EF), receiver operating characteristic curve (ROC), Boltzmann-enhanced discrimination of receiver operating characteristic (BEDROC), and area under accumulation curve (AUAC). Most notably, the compounds’ pIC50 values were predicted by a machine learning-based model generated by the AutoQSAR algorithm. The generated model was validated to affirm its predictive model. The best models achieved for AChE, BChE and MAO were models kpls_radial_17 (R2 = 0.86 and Q2 = 0.73), pls_38 (R2 = 0.77 and Q2 = 0.72), kpls_desc_44 (R2 = 0.81 and Q2 = 0.81) and these externally validated models were utilized to predict the bioactivities of the lead compounds. The binding affinity results of the ligands against the three selected targets revealed that luteolin displayed the highest affinity score of −9.60 kcal/mol, closely followed by apigenin and ellagic acid with docking scores of −9.60 and −9.53 kcal/mol, respectively. The least binding affinity was attained by gallic acid (−6.30 kcal/mol). The docking scores of our standards were −10.40 and −7.93 kcal/mol for donepezil and galanthamine, respectively. The toxicity prediction revealed that none of the flavonoids presented toxicity and they all had good absorption parameters for the analyzed targets. Hence, these compounds can be considered as likely leads for drug improvement against the same.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Deciphering the Interactions of Bioactive Compounds in Selected Traditional Medicinal Plants against Alzheimer’s Diseases via Pharmacophore Modeling, Auto-QSAR, and Molecular Docking Approaches

Ojo

Okolie

et al. 2021

Molecules

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“…Medicinal plants are made up of various chemical constitutes that works independently, supplement or in synergy to improve health [3]. These natural plant-derived medicines that have been used in the remedy of various health problems, have a safe profile, they are gentle, cost-effective and easily accessible; and this has encouraged self-medication without consulting a medical practitioner [33][34][35][36].…”

Section: Phytopharmacology and Head And Neck Cancermentioning

confidence: 99%

Phytodentistry in Africa: prospects for head and neck cancers

et al. 2021

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Background Orthodox dentistry has undergone significant changes in recent times with the introduction of various omics and molecular targeted therapies both at the experimental/trial and clinical implementation level. Although, significant milestones have been achieved in the molecular dentistry field in the past decade, there remains a dearth of application of phytopharmacological innovation in personalized and targeted therapies for dental diseases. Main body From time immemorial, plant products have long been an integral aspect of dental practice ranging from chewing sticks/herbal kinds of toothpaste to dental/impression materials. The current era of precision medicine seeks to apply a multipronged molecular and bio-computational approaches to solve fundamental medical problems that have hitherto remained difficult. Remarkable changes in the molecular/omics era, have transformed empirical therapies into personalized/individualized ones. Furthermore, the combinatorial application and the widespread introduction of high-throughput molecular tools such as pharmacogenomics, phytopharmacology, metabolomics, mathematical modelling, and genetic engineering inter alia, has tremendously improved the diagnostic and therapeutic landscape of medicine. Additionally, the variable molecular epidemiology of diseases among different population and emerging molecular evidence warrants the use of customized novel theranostic techniques. Unfortunately, the footprint of such emerging application is sparse in dental diseases such as maxillofacial cancers. Conclusion Hence, this review seeks to evaluate the potential application of phytopharmacological approaches to head and neck cancers in a resource-limited environment, such as Africa.

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“…To simulate binding affinity between the receptor protein and bioactive compounds, the docking tool, AutoDock Vina (version 1.1.2), was used (Ojo et al, 2019). Piperine, pipercide, piperlongumine, and pyrimethamine were firstly docked into the target protein active sites using AutoDock Vina.…”

Section: Docking Studiesmentioning

confidence: 99%

“…For this study, AdmetSAR (predated.bmdrc.kr) and SwissADME (http://www. swissadme.ch) servers were utilized to speculate and outline vital drug-likeness like harmful dosage level, mutagenicity, and pharmacokinetically pertinent attributes of all the bioactive compounds (Ojo et al, 2019).…”

Section: Predictions Of Absorption Distribution Metabolism Excretion and Toxicity (Admet)mentioning

confidence: 99%

Exploring the potentials of selected bioactive compounds isolated from Piper guineense Schumach. & Thonn. leaf toward identification of novel pfDHFR and pfDHODH inhibitors as antimalaria agents

Adeleke¹

2021

J Appl Pharm Sci

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Present antimalarial drugs have been related to several adverse side effects, including headache, depression, nausea, and itchy skin. Thus, exploring bioactive compounds from a natural origin, which possess drug-like properties with no side effects, is of great importance. This study was designed to assess the molecular relations obtainable between piperine, pipercide, and piperlongumine compounds isolated from Piper guineense Schumach. & Thonn. leaf and targeted receptor linked to malaria Plasmodium falciparum dihydrofolate reductase (pfDHFR) and Plasmodium falciparum dihydroorotate dehydrogenase (pfDHODH) for antimalarial properties. The result showed that piperine (−8.3 kcal/mol) from P. guineense binds to pfDHFR with high affinity and low free energy than the other compounds and standard ligand pyrimethamine (−7.8 kcal/mol). In contrast, pyrimethamine (−8.4 kcal/mol) and pipercide (−8.3 kcal/mol) show a better binding affinity to pfDHODH. Hence, the results provided insights into the development of better piperine and pipercide as a replacement to present antimalarial agents, with further analysis worth considering.

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Spondias mombimL. (Anacardiaceae): Chemical fingerprints, inhibitory activities, and molecular docking on key enzymes relevant to erectile dysfunction and Alzheimer’s diseases

Cited by 19 publications

References 71 publications

Deciphering the Interactions of Bioactive Compounds in Selected Traditional Medicinal Plants against Alzheimer’s Diseases via Pharmacophore Modeling, Auto-QSAR, and Molecular Docking Approaches

Deciphering the Interactions of Bioactive Compounds in Selected Traditional Medicinal Plants against Alzheimer’s Diseases via Pharmacophore Modeling, Auto-QSAR, and Molecular Docking Approaches

Phytodentistry in Africa: prospects for head and neck cancers

Exploring the potentials of selected bioactive compounds isolated from Piper guineense Schumach. & Thonn. leaf toward identification of novel pfDHFR and pfDHODH inhibitors as antimalaria agents

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