Publications by authors named "Temitope Isaac Adelusi"

12 Publications

  • Page 1 of 1

A secondary approach with conventional medicines and supplements to recuperate current COVID-19 status.

Biomed Pharmacother 2021 Jul 27;142:111956. Epub 2021 Jul 27.

School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address:

Novel coronavirus 2019 (COVID-19) is a zoonosis that revised the global economic and societal progress since early 2020. The SARS-CoV-2 has been recognized as the responsible pathogen for COVID-19 with high infection and mortality rate potential. It has spread in 192 countries and infected about 1.5% of the world population, and still, a proper therapeutic approach is not unveiled. COVID-19 indication starts with fever to shortness of breathing, leading to ICU admission with the ventilation support in severe conditions. Besides the symptomatic mainstay clinical therapeutic approach, only Remdesivir has been approved by the FDA. Several pharmaceutical companies claimed different vaccines with exceptionally high efficacy (90-95%) against COVID-19; how long these vaccines can protect and long-term safety with the new variants are unpredictable. After the worldwide spread of the COVID-19 pandemic, numerous clinical trials with different phases are being performed to find the most appropriate solution to this condition. Some of these trials with old FDA-approved drugs showed promising results. In this review, we have precisely compiled the efforts to curb the disease and discussed the clinical findings of Ivermectin, Doxycycline, Vitamin-D, Vitamin-C, Zinc, and cannabidiol and their combinations. Additionally, the correlation of these molecules on the prophylactic and diseased ministration against COVID-19 has been explored.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2021.111956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313489PMC
July 2021

Exploring the inhibitory potentials of bioactive compounds against Keap1-Kelch protein using computational approaches.

In Silico Pharmacol 2021 25;9(1):39. Epub 2021 Jun 25.

Laboratory of Molecular Biology, Immunology and Bioinformatics, Department of Microbiology, Adeleke University, Ede, Osun State Nigeria.

The search for Keap1 inhibitors as potential Nrf2 activator is a way of increasing the antioxidant status of the human cellular environ. In this research, we used in silico methods to investigate Keap1-kelch inhibitory potential of bioactive compounds in order to predict their Nrf2 activating potential. ADMET profiling, physicochemical properties, molecular docking, molecular dynamics, and Molecular Mechanics-Poisson Boltzmann Surface Area (g_MMPBSA) free energy calculation studies were executed to drive home our aim. Out of all the bioactive compounds of , catechin (CAT) and chlorogenic acid (CGA) were selected based on their ADMET profile, physicochemical properties, and molecular docking analysis. Molecular docking studies of CAT and CGA to Keap1 kelch domain showed that they have - 9.2 kJ/mol and - 9.1 kJ/mol binding energies respectively with CAT having four hydrogen bond interactions with Keap1 while CGA had three. Analysis after the 30 ns molecular dynamics simulation revealed that CAT and CGA were both stable, although with minimal conformational alterations at the kelch pocket of Keap1. Finally, MMPBSA calculation of the Gibbs free energy of each amino acid interaction with CAT and CGA revealed that CAT had a higher total binding energy than CGA. Therefore, the Keap1 inhibitory capacities and the molecular dynamic characters of CAT and CGA at the Kelch domain of Keap1 suggest a putative Nrf2 signaling activating prowess.

Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-021-00100-2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40203-021-00100-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233444PMC
June 2021

Molecular dynamics, quantum mechanics and docking studies of some Keap1 inhibitors - An insight into the atomistic mechanisms of their antioxidant potential.

Heliyon 2021 Jun 16;7(6):e07317. Epub 2021 Jun 16.

Biophysical and Computational Chemistry Unit, Department of Pure and Applied Chemistry, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.

Inhibitors of Keap1 would disrupt the covalent interaction between Keap1 and Nrf2 to unleash Nrf2 transcriptional machinery that orchestrates its cellular antioxidant, cytoprotective and detoxification processes thereby, protecting the cells against oxidative stress mediated diseases. In this research, we investigated the Keap1 inhibiting potential of fifty (50) antioxidants using pharmacokinetic ADMET profiling, bioactivity assessment, physicochemical studies, molecular docking investigation, molecular dynamics and Quantum mechanical-based Density Functional Theory (DFT) studies using Keap1 as the apoprotein control. Out of these 50 antioxidants, Maslinic acid (MASA), 18-alpha-glycyrrhetinic acid (18-AGA) and resveratrol stand out by passing the RO5 (Lipinski rule of 5) for the physicochemical properties and ADMET studies. These three compounds also show high binding affinity of -10.6 kJ/mol, -10.4 kJ/mol and -7.8 kJ/mol at the kelch pocket of Keap1 respectively. Analysis of the 20ns trajectories using RMSD, RMSF, ROG and h-bond parameters revealed the stability of these compounds after comparing them with Keap1 apoprotein. Furthermore, the electron donating and accepting potentials of these compounds was used to investigate their reactivity using Density Functional Theory (HOMO and LUMO) and it was revealed that resveratrol had the highest stability based on its low energy gap. Our results predict that the three compounds are potential drug candidates with domiciled therapeutic functions against oxidative stress-mediated diseases. However, resveratrol stands out as the compound with the best stability and therefore, could be the best candidate with the best therapeutic efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.heliyon.2021.e07317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233138PMC
June 2021

Direct Keap1-kelch inhibitors as potential drug candidates for oxidative stress-orchestrated diseases: A review on In silico perspective.

Pharmacol Res 2021 05 24;167:105577. Epub 2021 Mar 24.

Computational Biology/Drug Discovery Laboratory, Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Nigeria; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China. Electronic address:

The recent outcry in the search for direct keap1 inhibitors requires a quicker and more effective drug discovery process which is an inherent property of the Computer Aided Drug Discovery (CADD) to bring drug candidates into the clinic for patient's use. This Keap1 (negative regulator of ARE master activator) is emerging as a therapeutic strategy to combat oxidative stress-orchestrated diseases. The advances in computer algorithm and compound databases require that we highlight the functionalities that this technology possesses that can be exploited to target Keap1-Nrf2 PPI. Therefore, in this review, we uncover the in silico approaches that had been exploited towards the identification of keap1 inhibition in the light of appropriate fitting with relevant amino acid residues, we found 3 and 16 other compounds that perfectly fit keap1 kelch pocket/domain. Our goal is to harness the parameters that could orchestrate keap1 surface druggability by utilizing hotspot regions for virtual fragment screening and identification of hotspot residues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2021.105577DOI Listing
May 2021

In silico investigation of saponins and tannins as potential inhibitors of SARS-CoV-2 main protease (M).

In Silico Pharmacol 2021 6;9(1). Epub 2021 Jan 6.

Department of Chemistry, Ekiti State University, Ado Ekiti, Ekiti State Nigeria.

It is no longer news that a novel strain of coronavirus named SARS-CoV-2 is ravaging the health sector worldwide, several attempts have been made to curtail this pandemic via repurposing of old drugs but at the present, available drugs are not adequately effective. Over the years, plant phytochemicals are increasingly becoming alternative sources of antimicrobial agents with novel mechanisms of action and limited side effects compared to synthetic drugs. Isolated saponins and tannins were evaluated for antiviral activity against SARS-CoV-2 (M) via Molecular Docking and it was observed that a handsome number of the phytochemicals had binding affinities much better than Remdesivir, Dexamethasone, and N3 inhibitor which were used as the standards in this study. Further investigation of drug-likeness, ADMET profile, PASS profile, oral bioavailability, bioactivity, binding mode, and molecular interactions of these phytochemicals revealed that binding affinity alone is not enough to justify the potency of a molecule in the drug discovery process, as only 4 among the screened compounds passed all the analyses and are identified as potential inhibitors of SARS-CoV-2 (M). This preliminary study thereby recommends Ellagic acid (- 8.4 kcal/mol), Arjunic Acid (- 8.1 kcal/mol), Theasapogenol B (- 8.1 kcal/mol), and Euscaphic Acid (- 8.0 kcal/mol) as potential inhibitors of SARS-CoV-2 (M) with better pharmacokinetics and bioavailability compared to Remdesivir which is currently used compassionately.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40203-020-00071-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786323PMC
January 2021

Signaling pathways and proteins targeted by antidiabetic chalcones.

Life Sci 2020 Dec 30:118982. Epub 2020 Dec 30.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China. Electronic address:

Chalcones have shown a broad spectrum of biological activities with clinical potential against various diseases. The biological activities are mainly attributed to the presence of α, β-unsaturated carbonyl system, perceived as potential Michael acceptors. In this review, we discussed the antioxidant potential of chalcones and elucidated the mechanisms of pathways and proteins such as carbohydrate digestive enzymes (α-amylase and α-glucosidase), aldose reductase, SGLT-2, and Nrf2 that are targeted by antidiabetic chalcones. In addition to their insulin mimetic potential, we explore the major molecular targets of chalcones and discuss the biochemical and therapeutic implication of modulating these targets. Finally, we dwell on the opulence of the literature and envisage how RNA interference-mediated gene silencing technique and in silico molecular docking could be exploited in the search for novel and more efficacious antidiabetic chalcones.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2020.118982DOI Listing
December 2020

Neurotrophic, anti-neuroinflammatory, and redox balance mechanisms of chalcones.

Eur J Pharmacol 2021 Jan 27;891:173695. Epub 2020 Oct 27.

Laboratory of Functional and Structural Biochemistry, Federal University of São Carlos, Rodovia Washington Luís, km 235, São Carlos, São Paulo, Brazil. Electronic address:

The passage of time that evoke aging; the tilted redox balance that contribute oxidative entropy; the polarization of microglia cells that produce inflammatory phenotype; all represent the intricacies of CNS-dependent disease progression. Neurological diseases that result from CNS injury raise social concerns and the available therapeutic strategies are frustrated by low efficacy, high toxicity, and multiple side effects. However, emergent studies have shown the neuroprotective role of natural compounds - including chalcones - with high efficacy in the protection of CNS structures. These compounds reportedly demonstrate neurotrophic mechanism through the upregulation of neurotrophic factors, anti-apoptotic Bcl-2, and downregulation of Bax protein; anti-neuroinflammatory mechanism via the inhibition of neuroinflammatory pathways, attenuated secretion of pro-inflammatory cytokines, prevention of blood brain barrier (BBB) disruption, and protection against nerve senescence; antioxidant mechanism through the upregulation of Nrf2 activities, inhibition of Keap1, synthesis of antioxidant enzymes, and maintenance of high antioxidant/oxidant ratio. All these mechanisms represent chalcones' neuroprotective mechanisms. In this review, we highlight different pathways involved in CNS-related diseases and elucidate various mechanisms by which chalcones can perturb these shunts as a potential therapeutic modality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejphar.2020.173695DOI Listing
January 2021

AMPK allostery: A therapeutic target for the management/treatment of diabetic nephropathy.

Life Sci 2020 Nov 18;261:118455. Epub 2020 Sep 18.

Computational Biology/Drug Discovery Laboratory, Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Nigeria; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China. Electronic address:

Diabetic nephropathy (DN) is a chronic complication of diabetes mellitus (DM) with approximately 30-40% of patients with DM developing nephropathy, and it is the leading cause of end-stage renal diseases and diabetic morbidity. The pathogenesis of DN is primarily associated with irregularities in the metabolism of glucose and lipid leading to hyperglycemia-induced oxidative stress, which has been a major target together with blood pressure regulation in the control of DN progression. However, the regulation of 5' adenosine monophosphate-activated protein kinase (AMPK), a highly conserved protein kinase for maintaining energy balance and cellular growth and repair has been implicated in the development of DM and its complications. Therefore, targeting AMPK pathway has been explored as a therapeutic strategy for the treatment of diabetes and its complication, although most of the mechanisms have not been fully elucidated. In this review, we discuss the structure of AMPK relevant to understanding its allosteric regulation and its role in the pathogenesis and progression of DN. We also identify therapeutic agents that modulate AMPK and its downstream targets with their specific mechanisms of action in the treatment of DN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2020.118455DOI Listing
November 2020

Keap1/Nrf2/ARE signaling unfolds therapeutic targets for redox imbalanced-mediated diseases and diabetic nephropathy.

Biomed Pharmacother 2020 Mar 13;123:109732. Epub 2020 Jan 13.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China. Electronic address:

Hyperglycemia/oxidative stress has been implicated in the initiation and progression of diabetic complications while the components of Keap1/Nrf2/ARE signaling are being exploited as therapeutic targets for the treatment/management of these pathologies. Antioxidant agents like drugs, nutraceuticals and pure compounds that target the proteins of this pathway and their downstream genes hold the therapeutic strength to put the progression of this disease at bay. Here, we elucidate how the modulation of Keap1/Nrf2/ARE had been exploited for the treatment/management of end-stage diabetic kidney complication (diabetic nephropathy) by looking into (1) Nrf2 nuclear translocation and phosphorylation by some protein kinases at specific amino acid sequences and (2) Keap1 downregulation/Keap1-Nrf2 protein-protein inhibition (PPI) as potential therapeutic mechanisms exploited by Nrf2 activators for the modulation of diabetic nephropathy biomarkers (Collagen IV, Laminin, TGF-β1 and Fibronectin) that ultimately lead to the amelioration of this disease progression. Furthermore, we brought to limelight the relationship between diabetic nephropathy and Keap1/Nrf2/ARE and finally elucidate how the modulation of this signaling pathway could be further explored to create novel therapeutic milestones.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2019.109732DOI Listing
March 2020

Quantitative profiling of neurotransmitter abnormalities in brain, cerebrospinal fluid, and serum of experimental diabetic encephalopathy male rat.

J Neurosci Res 2018 01 13;96(1):138-150. Epub 2017 Jun 13.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, China.

Diabetic encephalopathy (DE), one of the most prevalent chronic complications of diabetes mellitus, is short of effective prevention and formidable therapeutic strategies. The aim of the present study is to reveal the imbalance of tryptophan (Trp) and its metabolites in streptozotocin (STZ)-induced experimental DE rats to underscore their critical values in clinical diagnosis of the disease. For this purpose, we first developed an accurate and appropriate simultaneous method for measuring Trp and its metabolites using liquid chromatography-tandem mass spectrometry, which was in accordance with the requirements of biological sample analysis. Secondly, a single STZ intraperitoneal injection was administered to male Sprague-Dawley rats, and their cognitive function was detected by Morris water maze tests. Cerebrospinal fluid (CSF), serum, and brain tissue were then collected for the determination of Trp and its metabolites. Compared with age-matched control rats, the levels of neuroprotective serotonin decreased significantly in the samples of cortices, hippocampi, striatum, CSF, and serums in the STZ-induced DE rats, while the levels of neurotoxic 3-hydroxykynurenine increased significantly. Moreover, analogous changes of both compounds were found in the central nervous system and peripheral blood of the STZ-induced DE rats. In conclusion, we established a quantitative method for the simultaneous detection of Trp and its metabolites, and we also present a critical elucidation of the nervous system dysfunction in DE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jnr.24098DOI Listing
January 2018

A variation in KCNQ1 gene is associated with repaglinide efficacy on insulin resistance in Chinese Type 2 Diabetes Mellitus Patients.

Sci Rep 2016 11 18;6:37293. Epub 2016 Nov 18.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, People's Republic of China.

Repaglinide is an insulin secretagogue that often exhibits considerable interindividual variability in therapeutic efficacy. The current study was designed to investigate the impact of KCNQ1 genetic polymorphism on the efficacy of repaglinide and furthermore to identify the potential mechanism of action in patients with type 2 diabetes. A total of 305 patients and 200 healthy subjects were genotyped for the KCNQ1 rs2237892 polymorphism, and 82 patients with T2DM were randomized for the oral administration of repaglinide for 8 weeks. HepG2 cells were incubated with repaglinide in the absence or presence of a KCNQ1 inhibitor or the pcDNA3.1-hKCNQ1 plasmid, after which the levels of Akt, IRS-2 and PI(3)K were determined. Our data showed that repaglinide significantly decreased HOMA-IR in patients with T2DM. Furthermore, the level of HOMA-IR was significantly reduced in those patients with CT or TT genotypes than CC homozygotes. The KCNQ1 inhibitor enhanced repaglinide efficacy on insulin resistance, with IRS-2/PI(3)K/Akt signaling being up-regulated markedly. As in our clinical experiment, these data strongly suggest that KCNQ1 genetic polymorphism influences repaglinide response due to the pivotal role of KCNQ1 in regulating insulin resistance through the IRS-2/PI(3)K/Akt signaling pathway. This study was registered in the Chinese Clinical Trial Register on May 14, 2013. (No. ChiCTR-CCC13003536).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep37293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114551PMC
November 2016

Antihyperlipidemic and antiatherogenic activity of simvastatin may involve modulation of the expression of lecithin:cholesterol acyl transferase.

Acta Biochim Pol 2013 22;60(4):579-83. Epub 2013 Nov 22.

Department of Biochemistry, Ladoke Akintola University of Technology, Nigeria.

Introduction: The statin-induced effects on high density lipoprotein (HDL) are relatively small compared with those of low density lipoprotein (LDL) and, as a result, most clinical trials of statins are underpowered with respect to HDL parameters. This study experimentally investigated, the effects of statin on serum lipids, atherogenic index and examined the possibility of a relationship amongst serum concentrations of HDL-C, atherogenic index and activity of lecithin:cholesterol acyl transferase.

Method: Thirty albino rats equally divided into 2 groups were used for the study. Group 1 was given 0.05mg/g of statin daily for 28 days, while group 2 served as control. HDL concentration was determined as a measure of HDL-C. Total cholesterol (TC), triglyceride (TG) and HDL-C were determined spectrophotometrically while LDL-C was calculated using the Frieldwald formula. Effect on the activity of lecithin:cholesterol acyl transferase was determined by the difference between the amount of free cholesterol converted to cholesteryl ester in the two experimental groups. Effects on body and relative organs weights were also determined.

Results: The administration of statin caused a significant increase in serum concentration of HDL-C, while levels of LDL-C, triglyceride and total cholesterol were reduced. Simvastatin caused a significant reduction in the atherogenic index (TC/HDL-C; LDLC/HDL-C). The administration of statin significantly induced the activity of lecithin:cholesterol acyl transferase (LCAT) as evident by reduced serum concentration of free cholesterol when compared with control. The administration of statin caused reduced body and relative organs weights.

Conclusion: The study showed that serum antihyperlipidemic and antiatherogenic activity of statin may involve the induction of LCAT.
View Article and Find Full Text PDF

Download full-text PDF

Source
August 2014
-->