A Computational QSAR, Molecular Docking and In Vitro Cytotoxicity Study of Novel Thiouracil-Based Drugs with Anticancer Activity against Human-DNA Topoisomerase II

Khaled, Doaa M.; Elshakre, Mohamed E.; Noamaan, Mahmoud A.; Butt, Haider; Abdel Fattah, Marwa M.; Gaber, Dalia A.

doi:10.3390/ijms231911799

Open AccessArticle

A Computational QSAR, Molecular Docking and In Vitro Cytotoxicity Study of Novel Thiouracil-Based Drugs with Anticancer Activity against Human-DNA Topoisomerase II

by

Doaa M. Khaled

¹

,

Mohamed E. Elshakre

^2,*

,

Mahmoud A. Noamaan

³

,

Haider Butt

⁴

,

Marwa M. Abdel Fattah

⁵ and

Dalia A. Gaber

^6,7,*

¹

Histology and Cytology Department, Faculty of Medicine, Helwan University, Cairo 11795, Egypt

²

Chemistry Department, Faculty of Science, Cairo University, Cairo 12613, Egypt

³

Mathematics Department, Faculty of Science, Cairo University, Cairo 12613, Egypt

⁴

Department of Mechanical Engineering, Khalifa University, Abu Dhabi 127788, United Arab Emirates

⁵

Histology and Cytology Department, Faculty of Medicine, Misr University for Science & Technology, Cairo P.O. Box 77, Egypt

⁶

Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Helwan University, Cairo 11795, Egypt

⁷

Department of Biomedical Sciences, College of Medicine, Gulf Medical University, Ajman 4184, United Arab Emirates

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2022, 23(19), 11799; https://doi.org/10.3390/ijms231911799

Submission received: 26 August 2022 / Revised: 16 September 2022 / Accepted: 18 September 2022 / Published: 5 October 2022

(This article belongs to the Special Issue New Avenues in Molecular Docking for Drug Design 2022)

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Abstract

Computational chemistry, molecular docking, and drug design approaches, combined with the biochemical evaluation of the antitumor activity of selected derivatives of the thiouracil-based dihydroindeno pyrido pyrimidines against topoisomerase I and II. The IC50 of other cell lines including the normal human lung cell line W138, lung cancer cell line, A549, breast cancer cell line, MCF-7, cervical cancer, HeLa, and liver cancer cell line HepG2 was evaluated using biochemical methods. The global reactivity descriptors and physicochemical parameters were computed, showing good agreement with the Lipinski and Veber’s rules of the drug criteria. The molecular docking study of the ligands with the topoisomerase protein provides the binding sites, binding energies, and deactivation constant for the inhibition pocket. Various biochemical methods were used to evaluate the IC50 of the cell lines. The QSAR model was developed for colorectal cell line HCT as a case study. Four QSAR statistical models were predicted between the IC50 of the colorectal cell line HCT to correlate the anticancer activity and the computed physicochemical and quantum chemical global reactivity descriptors. The predictive power of the models indicates a good correlation between the observed and the predicted activity.

Keywords: QSAR; molecular docking; in vitro cytotoxicity; topoisomerase II; anticancer therapy

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MDPI and ACS Style

Khaled, D.M.; Elshakre, M.E.; Noamaan, M.A.; Butt, H.; Abdel Fattah, M.M.; Gaber, D.A. A Computational QSAR, Molecular Docking and In Vitro Cytotoxicity Study of Novel Thiouracil-Based Drugs with Anticancer Activity against Human-DNA Topoisomerase II. Int. J. Mol. Sci. 2022, 23, 11799. https://doi.org/10.3390/ijms231911799

AMA Style

Khaled DM, Elshakre ME, Noamaan MA, Butt H, Abdel Fattah MM, Gaber DA. A Computational QSAR, Molecular Docking and In Vitro Cytotoxicity Study of Novel Thiouracil-Based Drugs with Anticancer Activity against Human-DNA Topoisomerase II. International Journal of Molecular Sciences. 2022; 23(19):11799. https://doi.org/10.3390/ijms231911799

Chicago/Turabian Style

Khaled, Doaa M., Mohamed E. Elshakre, Mahmoud A. Noamaan, Haider Butt, Marwa M. Abdel Fattah, and Dalia A. Gaber. 2022. "A Computational QSAR, Molecular Docking and In Vitro Cytotoxicity Study of Novel Thiouracil-Based Drugs with Anticancer Activity against Human-DNA Topoisomerase II" International Journal of Molecular Sciences 23, no. 19: 11799. https://doi.org/10.3390/ijms231911799

APA Style

Khaled, D. M., Elshakre, M. E., Noamaan, M. A., Butt, H., Abdel Fattah, M. M., & Gaber, D. A. (2022). A Computational QSAR, Molecular Docking and In Vitro Cytotoxicity Study of Novel Thiouracil-Based Drugs with Anticancer Activity against Human-DNA Topoisomerase II. International Journal of Molecular Sciences, 23(19), 11799. https://doi.org/10.3390/ijms231911799

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A Computational QSAR, Molecular Docking and In Vitro Cytotoxicity Study of Novel Thiouracil-Based Drugs with Anticancer Activity against Human-DNA Topoisomerase II

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