Publications by authors named "Adewale J Ogunleye"

7 Publications

  • Page 1 of 1

Genome-wide regulation of CpG methylation by ecCEBPα in acute myeloid leukemia.

F1000Res 2021 11;10:204. Epub 2021 Mar 11.

Department of Biological and Medical Physics, Moscow Institute of Physics and Technology, Moscow, Russian Federation.

Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by genetic and epigenetic aberrations that alter the differentiation capacity of myeloid progenitor cells. The transcription factor is frequently mutated in AML patients leading to an increase in DNA methylation in many genomic locations. Previously, it has been shown that (extra coding CEBP ) - a lncRNA transcribed in the same direction as gene - regulates DNA methylation of promoter in Here, we hypothesize that could participate in the regulation of DNA methylation in . : First, we retrieved the methylation profile of AML patients with mutated locus from The Cancer Genome Atlas (TCGA). We then predicted the secondary structure in order to check the potential of to form triplexes around CpG loci and checked if triplex formation influenced CpG methylation, genome-wide. Using DNA methylation profiles of AML patients with a mutated locus, we show that could interact with DNA by forming DNA:RNA triple helices and protect regions near its binding sites from global DNA methylation. Further analysis revealed that triplex-forming oligonucleotides in are structurally unpaired supporting the DNA-binding potential of these regions. triplexes supported with the RNA-chromatin co-localization data are located in the promoters of leukemia-linked transcriptional factors such as MLF2. Overall, these results suggest a novel regulatory mechanism for as a genome-wide epigenetic modulator through triple-helix formation which may provide a foundation for sequence-specific engineering of RNA for regulating methylation of specific genes.
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http://dx.doi.org/10.12688/f1000research.28146.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444155.2PMC
October 2021

Induced Fit Docking and Automated QSAR Studies Reveal the ER-α Inhibitory Activity of Cannabis sativa in Breast Cancer.

Recent Pat Anticancer Drug Discov 2021 ;16(2):273-284

Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, Ondo State, Nigeria.

Background: Breast Cancer (BC), a common fatal disease and the deadliest cancer next to lung cancer, is characterized by an abnormal growth of cells in the tissues of the breast. BC chemotherapy is marked by targeting the activities of some receptors such as Estrogen Receptor alpha (ER-α). At present, one of the most commonly used and approved marketed therapeutic drugs for BC is tamoxifen. Despite the short-term success of tamoxifen usage, its long time treatment has been associated with significant side effects. Therefore, there is a pressing need for the development of novel anti-estrogens for the prevention and treatment of BC.

Objective: In this study, we evaluate the inhibitory effect of Cannabis sativa phytoconstituents on ER-α.

Methods: Glide and induced fit docking followed by ADME, automated QSAR and binding free energy (Δ) studies were used to evaluate anti-breast cancer and ER-α inhibitory activity of Cannabis sativa, which has been reported to be effective in inhibiting breast cancer cell proliferation.

Results: Phyto-constituents of Cannabis sativa possess lower docking scores and good Δ when compared to that of tamoxifen. ADME and AutoQSAR studies revealed that our lead compounds demonstrated the properties required to make them promising therapeutic agents.

Conclusion: The results of this study suggest that naringenin, dihydroresveratrol, baicalein, apigenin and cannabitriol could have relatively better inhibitory activity than tamoxifen and could be a better and patent therapeutic candidate in the treatment of BC. Further research such as in vivo and/or in vitro assays could be conducted to verify the ability of these compounds.
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http://dx.doi.org/10.2174/1574892816666210201115359DOI Listing
January 2021

Molecular Docking, QSAR and Microscopic Studies of Anti-trypanosomal Compounds from the Pathogen Box.

Curr Comput Aided Drug Des 2021 ;17(3):378-386

Nigerian Institute for Trypanosomiasis Research, Vom, Plateau State, Nigeria.

Background: Trypanosoma brucei (T. brucei) is the cause of the deadly human African trypanosomiasis (HAT) with a case fatality ratio of 10%.

Objective: Targeting the essential Trypanosomal glucose metabolism pathway through the inhibition of phosphoglycerate kinase (PGK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a valid strategy for anti-T. brucei drug development.

Methods: Here, quantitative structure activity relationship, molecular docking and microscopic studies were used to describe the mode of inhibition of selected compounds from the pathogen box PGK and GAPDH.

Results: We identified 4 hit compounds from the pathogen box with optimal binding and chemical interactions. Notably, it was identified that interacting charge surface and atomic mass were key aspects of both PGK and GAPDH inhibition. Also, novel anti-trypanosomal compounds were identified from the pathogen box and their half maximal inhibitory concentrations were described.

Conclusion: Our study presents new anti-trypanosomal compounds with optimal pharmacological profiles and an optimization strategy for improving target specificity in the rational design of novel anti-trypanosomal compounds.
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http://dx.doi.org/10.2174/1573409916666200722140704DOI Listing
January 2021

Kaempferol as a Potential PAK4 Inhibitor in Triple Negative Breast Cancer: Extra Precision Glide Docking and Free Energy Calculation.

Curr Drug Discov Technol 2020 ;17(5):682-695

Department of Biochemistry, Lagos State University, Ojo, Lagos, Nigeria.

Background: P-21 activating kinase 4 (PAK4) is implicated in poor prognosis of many human tumors, particularly in Triple Negative Breast Cancer (TNBC) progression. Studies have revealed the crucial role of PAK4 in cell proliferation, anchorage-independent growth and cell migration among other hallmarks of cancer. Thus, PAK4 is an attractive target for anti-TNBC drug design and development. In our research, we used in silico methods to investigate the inhibitory potentials of kaempferol against PAK4 as compared with co-crystallized 4T6 and a standard PAK4 inhibitor-KPT-9274. The ligands were docked into the ATP-binding site of the target enzyme and post-docking validations were calculated.

Results: In the molecular docking results, kaempferol had higher affinity than the standard KPT-9274. However, the SP and XP docking scores for the co-crystallized 4T6 were the highest. The analyses of the docking showed a favorable interaction between kaempferol and the catalytic-important aminoacyl residues, especially GLU396, LEU398 and ASP458 in the ATP-binding site of PAK4 when compared with what was obtained in the 4T6-PAK4 complex. Molecular mechanics based MM-GBSA was used to validate docking results. The free energy calculations revealed that kaempferol may have a favorable biological activity. Furthermore, the druggability of each ligand was assessed using the QikProp module and the SwissADME online tool. Kaempferol possessed a propitious drug-like property when compared to the standard ligands.

Conclusions: We, therefore, put forward a logical argument that kaempferol can be further evaluated as a potential PAK4 inhibitor in TNBC.
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http://dx.doi.org/10.2174/1570163816666190823135948DOI Listing
September 2021

Molecular docking based screening analysis of GSK3B.

Bioinformation 2019 15;15(3):201-208. Epub 2019 Mar 15.

Centre for Biocomputing and Drug Discovery, Adekunle Ajasin University, Nigeria.

GSK3B has been an interesting drug target in the pharmaceutical industry. Its dysfunctional expression has prognostic significance in the top 3 cause of death associated with non-communicable diseases (cancer, Alzheimer's disease and type 2 diabetes). Previous studies have shown clearly that inhibiting GSK3B has proven therapeutic significance in Alzheimer's disease, but its contribution to various cancers has not been clearly resolved. In this study we report the contribution and prognostic significance of GSK3B to two breast cancer subtypes; ductal carcinoma in-situ (DCIS) and invasive ductal carcinoma (IDC) using the Oncomine platform. We performed high throughput screening using molecular docking. We identified BT-000775, a compound that was subjected to further computational hit optimization protocols. Through computational predictions, BT-000775 is a highly selective GSK3B inhibitor, with superior binding affinity and robust ADME profiles suitable for the patho-physiological presentations.
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http://dx.doi.org/10.6026/97320630015201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637402PMC
March 2019

Salient Aspects of PBP2A-inhibition; A QSAR Study.

Curr Comput Aided Drug Des 2018 ;14(4):363-369

Centre for Biocomputing and Drug Development, Adekunle Ajasin University, Akungba Akoko, Nigeria.

Background: Inhibition of penicillin binding protein 2A (PBP2A) represents a sound drug design strategy in combatting Methicillin resistant Staphylococcus aureus (MRSA). Considering the urgent need for effective antimicrobials in combatting MRSA infections, we have developed a statistically robust ensemble of molecular descriptors (1, 2, & 3-D) from compounds targeting PBP2A in vivo.

Methods: 37 (training set: 26, test set: 11) PBP2A-inhibitors were submitted for descriptor generation after which an unsupervised, non-exhaustive genetic algorithm (GA) was deployed for fishing out the best descriptor subset. Assignment of descriptors to a regression model was accomplished with the Partial Least Square (PLS) algorithm. At the end, an ensemble of 30 descriptors accurately predicted the ligand bioactivity, IC50 (R = 0.9996, R2 = 0.9992, R2 a = 0.9949, SEE =, 0.2297 Q2 LOO = 0.9741).

Results And Conclusion: Inferentially, we noticed that the overall efficacy of this model greatly depends on atomic polarizability and negative charge (electron) density. Besides the formula derived, the high dimensional model also offers critical insights into salient cheminformatics parameter to note during hit-to-lead PBP2A-antagonist optimization.
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http://dx.doi.org/10.2174/1573409914666180516114314DOI Listing
January 2019

flavanones; apposite inverse agonists of the β2-adrenergic receptor in asthma treatment.

Bioinformation 2018 28;14(2):60-67. Epub 2018 Feb 28.

Department of Chemical Sciences, Adekunle Ajasin University, Akungba Akoko, Ondo State, Nigeria.

Asthma is an inflammatory disease of the airway that poses a major threat to human health. With increase industrialization in the developed and developing countries, the incidence of asthma is on the rise. The β2-adrenergic receptor is an important target in designing anti-asthmatic drugs. The synthetic agonists of the β2-adrenergic receptor used over the years proved effective, but with indispensable side effects, thereby limiting their therapeutic use on a long-term scale. Inverse agonists of this receptor, although initially contraindicated, had been reported to have long-term beneficial effects. Phytochemicals from Agemone mexicana were screened against the human β2-adrenergic receptor in the agonist, inverse agonist, covalent agonist, and the antagonist conformations. Molecular docking of the phyto-constituents showed that the plant constituents bind better to the inverse agonist bound conformation of the protein, and revealed two flavanones; eriodictyol and hesperitin, with lower free energy (ΔG) values and higher affinities to the inverse agonist bound receptor than the co-crystallized ligand. Eriodictyol and hesperitin bind with the glide score of -10.684 and - 9.958 kcal/mol respectively, while the standard compound ICI-118551, binds with glide score of -9.503 kcal/mol. Further interaction profiling at the protein orthosteric site and ADME/Tox screening confirmed the drug-like properties of these compounds.
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http://dx.doi.org/10.6026/97320630014060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879945PMC
February 2018
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