OPEN ACCESS | PEER-REVIEWED | RESEARCH ARTICLE | DOWNLOAD PDF | VIEW FULL-TEXT PDF | TOTAL VIEWS
In silico evaluation and docking studies of pyrazole analogs as potential autophagy modulators against pancreatic cancer cell line MIA PaCa-2
Hiba Hashim Mahgoub Mohamed (1,*) , Amna Bint Wahab Elrashid Mohammed Hussien (2) , Ahmed Elsadig Mohammed Saeed (3)
(1) Department of Chemistry, College of Science, Sudan University of Science and Technology, 2288, Khartoum, Sudan
(2) College of Animal Production Science and Technology, Sudan University of Science and Technology, 2288, Khartoum, Sudan
(3) Department of Chemistry, College of Science, Sudan University of Science and Technology, 2288, Khartoum, Sudan
(*) Corresponding Author
Received: 28 Feb 2020 | Revised: 27 May 2020 | Accepted: 17 Jun 2020 | Published: 30 Sep 2020 | Issue Date: September 2020
A quantitative structure activity relationship (QSAR) model for a series of N-(1-benzyl-3,5-dimethyl-1H-pyrazole-4-yl) benzamide derivatives having autophagy inhibitory activities as potent anticancer agents was developed by the multiple linear regressions (MLR) method. In this study, previous compounds were used in the model development were divided into a set of fifteen compounds as training set and set of four compounds as test set. A model with high prediction ability and high correlation coefficients was obtained. This model showed r = 0.968, r2 = 0.937 and Q2 = 0.880, the QSAR model was also employed to predict the experimental compounds in an external test set, and to predict the activity of a new designed set of 3,5-dimethyl-4-substituted-pyrazole derivatives (1-15), result showed that compound 3 has the most promising inhibition activity (EC50 = 0.869 μM) against human pancreatic ductal adenocarcinoma cell MIA PaCa-2 compared to the reference chloroquine with (EC50 = 14 μM). Thus, the model showed good correlative and predictive ability. Docking studies was performed for designed compounds, docking analysis showed the best compound 1 with high docking affinity of -24.8616 kcal/mol.
Links for Article
| | | | | | |
| | | | | | |
Article MetricsThis Abstract was viewed 80 times | PDF Article downloaded 20 times
. Levine, B.; Kroemer, G. Cell 2008, 132(1), 27-42.
. Glick, D.; Barth, S.; Macleod, K. F. J. Pathol. 2010, 221(1), 3-12.
. Shintani, T.; Klionsky, D. J. Science 2004, 306(5698), 990-995.
. Li, W. W.; Li, J.; Bao, J. K. Cell. Mol. Life Sci 2012, 69(7), 1125-1136.
. Arias, E.; Cuervo, A. M. Curr. Opin. Cell Biol. 2011, 23(2), 184-189.
. Mizushima, N.; Komatsu, M. Cell 2011, 147, 728-741.
. Badadani, M. ISRN Cell Biology 2012, 2012, 1-11.
. Kaur, J.; Debnath, J. Nat. Rev. Mol. Cell Biol. 2015, 16(8), 461-472.
. Yu, L.; Chen, Y.; Tooze, S. A. Autophagy 2018, 14(2), 207-215.
. Kimmelman, A. C. Gene Dev. 2011, 25(19), 1999-2010.
. Yang, X.; Yu, D. D.; Yan, F.; Jing, Y. Y.; Han, Z. P.; Sun, K.; Liang, L.; Hou, J.; Wei, L. X. Cell Biosci. 2015, 5(1), 14.
. Gracio, D.; Magro, F.; Lima, R. T.; Maximo, V. Hematol. Med. Oncol. 2017, 2(1), 1-4.
. Marinkovic, M.; Sprung, M.; Buljubasic, M.; Novak, I. Oxid. Med. Cell Longev. 2018, 2018, 1-18.
. Hernandez, N.; Kiralj, R.; Ferreira, M. M.; Talavera, I. Chemometr. Intell. Lab. 2009, 98(1), 65-77.
. Hasegawa, K.; Yokoo, N.; Watanabe, K.; Hirata, M.; Miyashita, Y.; Sasaki, S. Chemometr. Intell. Lab. 1996, 33, 63-69.
. Soni, H. M.; Patel, P. K.; Chhabria, M. T.; Rana, D. N.; Mahajan, B. M.; Brahmkshatriya, P. S. Comp. Chem. 2015, 3, 45-53.
. Duchowicz, P. R.; Fioressi, S. E.; Castro, E.; Wróbel, K.; Ibezim, N. E.; Bacelo, D. E. ChemistrySelect 2017, 2(13), 3725-3731.
. Roy, K.; Kar, S.; Das, R. N. Statistical methods in QSAR/QSPR. In A primer on QSAR/QSPR modeling, Springer, Cham, 2015.
. Tong, W.; Xie, Q.; Hong, H.; Shi, L.; Fang, H.; Perkins, R. Environ. Health Persp. 2004, 112(12), 1249-1254.
. Veerasamy, R.; Rajak, H.; Jain, A.; Sivadasan, S.; Varghese, C. P.; Agrawal, R. K. Int. J. Drug Des. Discov. 2011, 3, 511-519.
. Golbraikh, A.; Tropsha, A. ACS Sym. Ser. 2002, 16, 357-396.
. Ai, T.; Willett, R.; Williams, J.; Ding, R.; Wilson, D. J.; Xie, J.; Kim, D. H.; Puertollano, R.; Chen, L. ACS Med. Chem. Lett 2016, 8(1), 90-95.
. Mauri, A.; Consonni, V.; Pavan, M.; Todeschini, R. MATCH Commun. Math. Comput. Chem. 2006, 56(2), 237-248.
How to cite
The other citation formats (EndNote | Reference Manager | ProCite | BibTeX | RefWorks) for this article can be found online at: How to cite item
DOI Link: https://doi.org/10.5155/eurjchem.11.3.187-193.1976
| | | | | | |
| | | | | |
Save to Zotero Save to Mendeley
European Journal of Chemistry 2020, 11(3), 187-193 | doi: https://doi.org/10.5155/eurjchem.11.3.187-193.1976 | Get rights and content
- There are currently no refbacks.
Copyright (c) 2020 Authors
This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at http://www.eurjchem.com/index.php/eurjchem/pages/view/terms and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0). By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License (http://www.eurjchem.com/index.php/eurjchem/pages/view/terms) are administered by Atlanta Publishing House LLC (European Journal of Chemistry).
© Copyright 2010 - 2020 • Atlanta Publishing House LLC • All Right Reserved.
The opinions expressed in all articles published in European Journal of Chemistry are those of the specific author(s), and do not necessarily reflect the views of Atlanta Publishing House LLC, or European Journal of Chemistry, or any of its employees.
Copyright 2010-2020 Atlanta Publishing House LLC. All rights reserved. This site is owned and operated by Atlanta Publishing House LLC whose registered office is 2850 Smith Ridge Trce Peachtree Cor GA 30071-2636, USA. Registered in USA.