Publications by authors named "Babatomiwa Kikiowo"

5 Publications

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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

Therapeutic potential of phyto-constituents against human pancreatic α-amylase.

J Biomol Struct Dyn 2020 Oct 15:1-12. Epub 2020 Oct 15.

Department of Biochemistry, Adekunle Ajasin University, Ondo State, Nigeria.

Type II Diabetes Mellitus (DM) is caused by insulin resistance in peripheral tissue and impaired insulin secretion through a dysfunction of the pancreatic β-cell. Acarbose is an anti-DM drug, it is effective but its continuous use may lead to undesirable side effects. Hence, the development of novel drugs from natural source that have both anti-diabetic and anti-oxidant activities, with little or no side effect during long-term use is of great importance. To investigate the anti-DM and anti-oxidant phyto-constituents of , e-pharmacophore model was generated using human pancreatic α-amylase (HPA) standard inhibitor, Acarbose to map important pharmacophoric features of HPA, and used to screen several phyto-constituents of to match at least 4 sites of the generated hypothesis. Glide and Induced Fit Docking followed by Prime MM-GBSA calculation, drug-likeness and ADME studies were employed for high fitness (>1.0) compounds retrieved from e-pharmacophore screening process. The drug-likeness properties of the lead compounds, Quercetin and Ombuin were analyzed taking into account the Lipinski's and Veber's rules. Further, machine-learning approach was used to generate QSAR model. The computed model, kpls_desc_19 was used to predict the bioactivity (pIC50) of Quercetin and Ombuin. Phyto-constituents of ; Quercetin and Ombuin have shown better and promising results when compared to that of the standard, acarbose. Based on the present study, orally delivered Quercetin and Ombuin from are relatively better inhibitor of HPA, thus they can be a useful therapeutic candidate in the management/treatment of DM when compared to acarbose.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1833758DOI Listing
October 2020

Flavones scaffold of as a potential xanthine oxidase inhibitor: Induced Fit Docking and ADME studies.

Bioimpacts 2020 2;10(4):227-234. Epub 2019 Nov 2.

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

Gout is a type of painful inflammation initiated by the interactions between monosodium urate crystals and connective tissue. Xanthine oxidase (XO) catalyzes the oxidation of hypoxanthine to xanthine, then to uric acid. The primary treatments for gout include XO inhibitors. At present, allopurinol is the most used XO inhibitor for the treatment of gout. However, it can cause adverse effects commonly known as allopurinol hypersensitivity syndrome, thereby limiting its usage. Consequently, it is necessary to develop potent and less toxic inhibitors of XO. is one of such plants under investigation for its diverse health benefits. Phytochemicals of were screened against XO receptor, using molecular docking. The top five hit compounds of glide docking yield flavones scaffold which were subjected to induced fit docking (IFD) and absorption, distribution, metabolism, and excretion (ADME) studies. The result showed that flavones scaffold of can bind with higher affinity and lower free energy values when compared to that of the standard, allopurinol. The IFD scores of the flavones scaffold range from -1525.25 to -1527.99 kcal/mol. Our results have shown that flavones scaffold might have the potential to act as an effective drug candidate when compared to allopurinol in treating and/or preventing gout and some inflammatory condition.
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http://dx.doi.org/10.34172/bi.2020.29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502905PMC
November 2019

Discovery of Traditional Chinese Medicine Derived Compounds as Wild Type and Mutant Plasmodium falciparum Dihydrofolate Reductase Inhibitors: Induced Fit Docking and ADME Studies.

Curr Drug Discov Technol 2021 ;18(4):554-569

Department of Biochemistry, Bioinformatics and Molecular Biology Unit, Federal University of Technology Akure, Ondo State, Nigeria.

Background: In a bid to come up with effective compounds as inhibitors for antimalarial treatment, we built a library of 2,000 traditional Chinese medicine(TCM)-derived compounds retrieved from TCM [email protected]

Methods: The active sites of both the wild type and mutant Plasmodium falciparum dihydrofolatereductase (pfDHFR) were explored using computational tools. pfDHFR, one of the prime drug targets in the prevention of malaria infection induced by the female anopheles mosquito has continued to offer resistance to drugs (antifolates) due to mutation in some of the key amino acid residues crucial for its inhibition.

Results: We utilized virtual throughput screening and glide XP docking to screen the compounds, and 8 compounds were found to have promising docking scores with both the wild type and mutant pfDHFR. They were further subjected to Induce Fit Docking (IFD) to affirm their inhibitory potency. The ADME properties and biological activity spectrum of the compounds were also considered. The inhibition profile of the compounds revealed that a number of compounds formed intermolecular interactions with ASP54, ILE14, LEU164, SER108/ASN108, ARG122 and ASP58. Most of the compounds can be considered as drug candidates due to their antiprotozoal activities and accordance with the Lipinski's Rule of Five (ROF).

Conclusion: The outcome of the present study should further be investigated to attest the efficacy of these compounds as better drug candidates than the antifolates.
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http://dx.doi.org/10.2174/1570163817999200729122753DOI Listing
January 2021

Molecular Docking and 3D Qsar Studies of C000000956 as a Potent Inhibitor of Bace-1.

Drug Res (Stuttg) 2019 Aug 19;69(8):451-457. Epub 2019 Feb 19.

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

Background: BACE-1 is an aspartate protease that is responsible for the proteolysis of amyloid precursor proteins (APP) into beta-amyloid (Aβ), a neurotoxic peptide in patients with Alzheimer's disease (AD). As such, BACE-1 is a prime pharmacological target in the control of Aβ in the brain and its inhibition will be a sound approach in AD therapy.

Methods: The computational pipeline which comprised molecular docking (MD), Quantitative Structure Activity Relationship (QSAR) modelling and Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) studies enabled the prediction of molecular interaction and relative inhibitory potentials of the hit compound.

Results And Discussion: The current study reports a naturally sourced small molecule inhibitor of BACE1 (C000000956) which was obtained through a computational pipeline. Also, pharmacological constraints such as pH dependent activity of the enzyme and blood brain barrier permeation which have been associated with the efficacy of previous BACE-1 inhibitors were well catered for. Our results suggest that orally delivered C000000956 is a potential small molecule inhibitor of BACE-1 which may find usefulness in AD-therapy.
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http://dx.doi.org/10.1055/a-0849-9377DOI Listing
August 2019
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