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






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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.


Keywords


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

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DOI: 10.5155/eurjchem.11.3.187-193.1976

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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 Nov. 2020
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)

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DOI Link: https://doi.org/10.5155/eurjchem.11.3.187-193.1976

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