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

Issue cover




Crossmark

  Open Access OPEN ACCESS | 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,*) orcid , Amna Bint Wahab Elrashid Mohammed Hussien (2) orcid , Ahmed Elsadig Mohammed Saeed (3) orcid

(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

Abstract


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.


Announcements


Our editors have decided to support scientists to publish their manuscripts in European Journal of Chemistry without any financial constraints.

1- The article processing fee will not be charged from the articles containing the single-crystal structure characterization or a DFT study between September 15, 2023 and October 31, 2023 (Voucher code: FALL2023).

2. A 50% discount will be applied to the article processing fee for submissions made between September 15, 2023 and October 31, 2023 by authors who have at least one publication in the European Journal of Chemistry (Voucher code: AUTHOR-3-2023).

3. Young writers will not be charged for the article processing fee between September 15, 2023 and October 31, 2023 (Voucher code: YOUNG2023).


Editor-in-Chief
European Journal of Chemistry

Keywords


QSAR; Cancer; Autophagy; MIA PaCa-2; Molecular modeling; Autophagy inhibitions

Full Text:

PDF
PDF    Open Access

DOI: 10.5155/eurjchem.11.3.187-193.1976

Links for Article


| | | | | | |

| | | | | | |

| | | |

Related Articles




Article Metrics

icon graph This Abstract was viewed 801 times | icon graph PDF Article downloaded 429 times


Citations

/


[1]. Rafael Fernades Costa, Larissa Córdova Turones, Keilah Valéria Naves Cavalcante, Ismael Aureliano Rosa Júnior, Carlos Henrique Xavier, Lucimar Pinheiro Rosseto, Hamilton Barbosa Napolitano, Patrícia Ferreira da Silva Castro, Marcos Luiz Ferreira Neto, Gustavo Mota Galvão, Ricardo Menegatti, Gustavo Rodrigues Pedrino, Elson Alves Costa, José Luis Rodrigues Martins, James Oluwagbamigbe Fajemiroye
Heterocyclic Compounds: Pharmacology of Pyrazole Analogs From Rational Structural Considerations
Frontiers in Pharmacology  12, , 2021
DOI: 10.3389/fphar.2021.666725
/


References


[1]. Levine, B.; Kroemer, G. Cell 2008, 132(1), 27-42.
https://doi.org/10.1016/j.cell.2007.12.018

[2]. Glick, D.; Barth, S.; Macleod, K. F. J. Pathol. 2010, 221(1), 3-12.
https://doi.org/10.1002/path.2697

[3]. Shintani, T.; Klionsky, D. J. Science 2004, 306(5698), 990-995.
https://doi.org/10.1126/science.1099993

[4]. Li, W. W.; Li, J.; Bao, J. K. Cell. Mol. Life Sci 2012, 69(7), 1125-1136.
https://doi.org/10.1007/s00018-011-0865-5

[5]. Arias, E.; Cuervo, A. M. Curr. Opin. Cell Biol. 2011, 23(2), 184-189.
https://doi.org/10.1016/j.ceb.2010.10.009

[6]. Mizushima, N.; Komatsu, M. Cell 2011, 147, 728-741.
https://doi.org/10.1016/j.cell.2011.10.026

[7]. Badadani, M. ISRN Cell Biology 2012, 2012, 1-11.
https://doi.org/10.5402/2012/927064

[8]. Kaur, J.; Debnath, J. Nat. Rev. Mol. Cell Biol. 2015, 16(8), 461-472.
https://doi.org/10.1038/nrm4024

[9]. Yu, L.; Chen, Y.; Tooze, S. A. Autophagy 2018, 14(2), 207-215.
https://doi.org/10.1080/15548627.2017.1378838

[10]. Kimmelman, A. C. Gene Dev. 2011, 25(19), 1999-2010.
https://doi.org/10.1101/gad.17558811

[11]. 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.
https://doi.org/10.1186/s13578-015-0005-2

[12]. Gracio, D.; Magro, F.; Lima, R. T.; Maximo, V. Hematol. Med. Oncol. 2017, 2(1), 1-4.
https://doi.org/10.15761/HMO.1000117

[13]. Marinkovic, M.; Sprung, M.; Buljubasic, M.; Novak, I. Oxid. Med. Cell Longev. 2018, 2018, 1-18.
https://doi.org/10.1155/2018/8023821

[14]. Hernandez, N.; Kiralj, R.; Ferreira, M. M.; Talavera, I. Chemometr. Intell. Lab. 2009, 98(1), 65-77.
https://doi.org/10.1016/j.chemolab.2009.04.012

[15]. Hasegawa, K.; Yokoo, N.; Watanabe, K.; Hirata, M.; Miyashita, Y.; Sasaki, S. Chemometr. Intell. Lab. 1996, 33, 63-69.
https://doi.org/10.1016/0169-7439(95)00071-2

[16]. Soni, H. M.; Patel, P. K.; Chhabria, M. T.; Rana, D. N.; Mahajan, B. M.; Brahmkshatriya, P. S. Comp. Chem. 2015, 3, 45-53.
https://doi.org/10.4236/cc.2015.34006

[17]. Duchowicz, P. R.; Fioressi, S. E.; Castro, E.; Wróbel, K.; Ibezim, N. E.; Bacelo, D. E. ChemistrySelect 2017, 2(13), 3725-3731.
https://doi.org/10.1002/slct.201700436

[18]. Roy, K.; Kar, S.; Das, R. N. Statistical methods in QSAR/QSPR. In A primer on QSAR/QSPR modeling, Springer, Cham, 2015.
https://doi.org/10.1007/978-3-319-17281-1

[19]. Tong, W.; Xie, Q.; Hong, H.; Shi, L.; Fang, H.; Perkins, R. Environ. Health Persp. 2004, 112(12), 1249-1254.
https://doi.org/10.1289/ehp.7125

[20]. Veerasamy, R.; Rajak, H.; Jain, A.; Sivadasan, S.; Varghese, C. P.; Agrawal, R. K. Int. J. Drug Des. Discov. 2011, 3, 511-519.

[21]. Golbraikh, A.; Tropsha, A. ACS Sym. Ser. 2002, 16, 357-396.
https://doi.org/10.1023/A:1020869118689

[22]. 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.
https://doi.org/10.1021/acsmedchemlett.6b00392

[23]. Mauri, A.; Consonni, V.; Pavan, M.; Todeschini, R. MATCH Commun. Math. Comput. Chem. 2006, 56(2), 237-248.


How to cite


Mohamed, H.; Hussien, A.; Saeed, A. Eur. J. Chem. 2020, 11(3), 187-193. doi:10.5155/eurjchem.11.3.187-193.1976
Mohamed, H.; Hussien, A.; Saeed, A. In silico evaluation and docking studies of pyrazole analogs as potential autophagy modulators against pancreatic cancer cell line MIA PaCa-2. Eur. J. Chem. 2020, 11(3), 187-193. doi:10.5155/eurjchem.11.3.187-193.1976
Mohamed, H., Hussien, A., & Saeed, A. (2020). In silico evaluation and docking studies of pyrazole analogs as potential autophagy modulators against pancreatic cancer cell line MIA PaCa-2. European Journal of Chemistry, 11(3), 187-193. doi:10.5155/eurjchem.11.3.187-193.1976
Mohamed, Hiba, Amna Bint Wahab Elrashid Mohammed Hussien, & Ahmed Elsadig Mohammed Saeed. "In silico evaluation and docking studies of pyrazole analogs as potential autophagy modulators against pancreatic cancer cell line MIA PaCa-2." European Journal of Chemistry [Online], 11.3 (2020): 187-193. Web. 28 Sep. 2023
Mohamed, Hiba, Hussien, Amna, AND Saeed, Ahmed. "In silico evaluation and docking studies of pyrazole analogs as potential autophagy modulators against pancreatic cancer cell line MIA PaCa-2" European Journal of Chemistry [Online], Volume 11 Number 3 (30 September 2020)

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


CrossRef | Scilit | GrowKudos | Researchgate | Publons | ScienceGate | Scite | Lens | OUCI

WorldCat Paperbuzz | LibKey Citeas | Dimensions | Semanticscholar | Plumx | Kopernio | Zotero | Mendeley

ZoteroSave to Zotero MendeleySave 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

Refbacks

  • There are currently no refbacks.




Copyright (c) 2020 Authors

Creative Commons License
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 - 2023  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 2010-2023 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.