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Anti-gastric cancer activity of 1,2,3-triazolo[4,5-d]pyrimidine hybrids (1,2,3-TPH): QSAR and molecular docking approaches
Gastric cancer as a dreaded disease which occurs in the digestive system of human being remain a threat to the medical world. Bioactivity of series of designed and synthesized molecular compounds containing triazole and pyrimidine moieties were subjected to quantum chemical calculations using B3LYP/...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090349/ https://www.ncbi.nlm.nih.gov/pubmed/32215327 http://dx.doi.org/10.1016/j.heliyon.2020.e03561 |
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author | Kolawole, Oyebamiji Abel Olatomide A, Fadare Banjo, Semire |
author_facet | Kolawole, Oyebamiji Abel Olatomide A, Fadare Banjo, Semire |
author_sort | Kolawole, Oyebamiji Abel |
collection | PubMed |
description | Gastric cancer as a dreaded disease which occurs in the digestive system of human being remain a threat to the medical world. Bioactivity of series of designed and synthesized molecular compounds containing triazole and pyrimidine moieties were subjected to quantum chemical calculations using B3LYP/6-31+G∗. The calculated molecular descriptors such as the E(HOMO) (eV), E(LUMO) (eV), band gap (eV), chemical hardness (η), global nucleophilicity, dipole moment (Debye), chemical potential, log P, molecular weight (amu) and Ovality. The descriptors that describe anti-gastric cancer activity of the studied compounds were used for QSAR analysis using SPSS and Gretl software packages for multiple linear regression (MLR), XLSTAT for partial least square (PLS) and MATLAB for artificial neural network (ANN). The methods (MLR, PLS, and ANN) were predictive. Nevertheless, ANN performed better than MLR and PLS. More so, molecular docking study was executed on the studied compounds and gastric cancer cell line (PDB ID:4oum); the docking studies showed that 2-(1-(2-(3-benzyl-5-(benzylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl)hydrazono)ethyl)phenol (A22) having the lowest binding affinity (-8.40 kcal/mol); this was correlated to the observed inhibitory activity of the compound against gastric cancer. Thus, it showed better inhibition than other studied compounds. The amino acid residues that were involved in stabilizing A22 in the active site of the 4oum are: VAL-9, ALA-10, THR-49, ASN-48, PRO-47 and TYR-46. Also, a good relationship was observed between the calculated binding affinity and the observed inhibition concentration (IC(50)). |
format | Online Article Text |
id | pubmed-7090349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-70903492020-03-25 Anti-gastric cancer activity of 1,2,3-triazolo[4,5-d]pyrimidine hybrids (1,2,3-TPH): QSAR and molecular docking approaches Kolawole, Oyebamiji Abel Olatomide A, Fadare Banjo, Semire Heliyon Article Gastric cancer as a dreaded disease which occurs in the digestive system of human being remain a threat to the medical world. Bioactivity of series of designed and synthesized molecular compounds containing triazole and pyrimidine moieties were subjected to quantum chemical calculations using B3LYP/6-31+G∗. The calculated molecular descriptors such as the E(HOMO) (eV), E(LUMO) (eV), band gap (eV), chemical hardness (η), global nucleophilicity, dipole moment (Debye), chemical potential, log P, molecular weight (amu) and Ovality. The descriptors that describe anti-gastric cancer activity of the studied compounds were used for QSAR analysis using SPSS and Gretl software packages for multiple linear regression (MLR), XLSTAT for partial least square (PLS) and MATLAB for artificial neural network (ANN). The methods (MLR, PLS, and ANN) were predictive. Nevertheless, ANN performed better than MLR and PLS. More so, molecular docking study was executed on the studied compounds and gastric cancer cell line (PDB ID:4oum); the docking studies showed that 2-(1-(2-(3-benzyl-5-(benzylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl)hydrazono)ethyl)phenol (A22) having the lowest binding affinity (-8.40 kcal/mol); this was correlated to the observed inhibitory activity of the compound against gastric cancer. Thus, it showed better inhibition than other studied compounds. The amino acid residues that were involved in stabilizing A22 in the active site of the 4oum are: VAL-9, ALA-10, THR-49, ASN-48, PRO-47 and TYR-46. Also, a good relationship was observed between the calculated binding affinity and the observed inhibition concentration (IC(50)). Elsevier 2020-03-20 /pmc/articles/PMC7090349/ /pubmed/32215327 http://dx.doi.org/10.1016/j.heliyon.2020.e03561 Text en © 2020 Published by Elsevier Ltd. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Kolawole, Oyebamiji Abel Olatomide A, Fadare Banjo, Semire Anti-gastric cancer activity of 1,2,3-triazolo[4,5-d]pyrimidine hybrids (1,2,3-TPH): QSAR and molecular docking approaches |
title | Anti-gastric cancer activity of 1,2,3-triazolo[4,5-d]pyrimidine hybrids (1,2,3-TPH): QSAR and molecular docking approaches |
title_full | Anti-gastric cancer activity of 1,2,3-triazolo[4,5-d]pyrimidine hybrids (1,2,3-TPH): QSAR and molecular docking approaches |
title_fullStr | Anti-gastric cancer activity of 1,2,3-triazolo[4,5-d]pyrimidine hybrids (1,2,3-TPH): QSAR and molecular docking approaches |
title_full_unstemmed | Anti-gastric cancer activity of 1,2,3-triazolo[4,5-d]pyrimidine hybrids (1,2,3-TPH): QSAR and molecular docking approaches |
title_short | Anti-gastric cancer activity of 1,2,3-triazolo[4,5-d]pyrimidine hybrids (1,2,3-TPH): QSAR and molecular docking approaches |
title_sort | anti-gastric cancer activity of 1,2,3-triazolo[4,5-d]pyrimidine hybrids (1,2,3-tph): qsar and molecular docking approaches |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090349/ https://www.ncbi.nlm.nih.gov/pubmed/32215327 http://dx.doi.org/10.1016/j.heliyon.2020.e03561 |
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