First-in-Class, Thiosemicarbazide-Based, Dual Inhibitors of Human DNA Topoisomerase IIα and Indoleamine-2,3-Dioxygenase 1 (IDO-1) with Strong Anticancer Properties †
1
Department of Clinical Genetics, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
2
Department of Pharmacology, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
*
Authors to whom correspondence should be addressed.
†
Presented at the 8th International Electronic Conference on Medicinal Chemistry, 1–30 November 2022; Available online: https://ecmc2022.sciforum.net/ .
Med. Sci. Forum 2022, 14(1), 15; https://doi.org/10.3390/ECMC2022-13268
Published: 1 November 2022
(This article belongs to the Proceedings of The 8th International Electronic Conference on Medicinal Chemistry)
Abstract
:According to a WHO report from 2020, cancer constitutes one of the leading causes of death worldwide. The number of cancer deaths is estimated to be approximately 10 million per year. These epidemiological data confirm that cancer is an increasingly global healthcare problem that needs urgent action. From a biological point of view, the basic feature of cancer is the uncontrolled growth and spread of abnormal cells from the place of origin to another part of the body. Inhibition of uncontrolled proliferation is one of the main goals of anticancer therapy. During our preliminary studies, we identified a group of thiosemicarbazide-based human DNA topoisomerase II inhibitors that decreased the viability of cancer cells and inhibited intracellular biosynthesis of their DNA much stronger than etoposide, i.e., clinically relevant topoisomerase II inhibitor. What is also important isthat the investigated compounds were recognized as topoisomerase II poisons because of their ability to stabilize the DNA-topoII cleavable complex. The investigated thiosemicarbazide derivatives were examined as potential anticancer agents against a panel of ten cancer cell lines. Moreover, we have discovered and described the first-in-class dual inhibitors of human DNA topoisomerase II/indoleamine-2,3-dioxygenase 1 (IDO1) that can lead to the future use of thiosemicarbazide derivatives as relevant components of anticancer immunotherapy.
Supplementary Materials
Conference poster. The material is available at https://www.mdpi.com/article/10.3390/ECMC2022-13268/s1.
Author Contributions
Conceptualization, B.K. and T.P.; methodology, B.K. and T.P.; validation, B.K. and T.P.; formal analysis, B.K. and T.P.; investigation, B.K. and T.P.; resources, B.K. and T.P.; data curation, B.K. and T.P.; writing—original draft preparation, B.K. and T.P.; writing—review and editing, B.K. and T.P.; visualization, B.K. and T.P.; supervision, T.P; project administration, B.K.; funding acquisition, B.K. All authors have read and agreed to the published version of the manuscript.
Funding
This research was funded by the National Science Centre, Poland, grant Preludium [UMO-2018/29/N/NZ7/01726]. IDO1/IDO2/TDO inhibition studies were financed from statutory fund (DS.544) of the Medical University of Lublin (Poland).
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
The authors confirm that all data underlying the findings are fully available . All data are included within the manuscript (DOI:10.1080/14756366.2022.2140420).
Conflicts of Interest
The authors declare no conflict of interest.
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MDPI and ACS Style
Kaproń, B.; Plech, T. First-in-Class, Thiosemicarbazide-Based, Dual Inhibitors of Human DNA Topoisomerase IIα and Indoleamine-2,3-Dioxygenase 1 (IDO-1) with Strong Anticancer Properties. Med. Sci. Forum 2022, 14, 15. https://doi.org/10.3390/ECMC2022-13268
AMA Style
Kaproń B, Plech T. First-in-Class, Thiosemicarbazide-Based, Dual Inhibitors of Human DNA Topoisomerase IIα and Indoleamine-2,3-Dioxygenase 1 (IDO-1) with Strong Anticancer Properties. Medical Sciences Forum. 2022; 14(1):15. https://doi.org/10.3390/ECMC2022-13268
Chicago/Turabian StyleKaproń, Barbara, and Tomasz Plech. 2022. "First-in-Class, Thiosemicarbazide-Based, Dual Inhibitors of Human DNA Topoisomerase IIα and Indoleamine-2,3-Dioxygenase 1 (IDO-1) with Strong Anticancer Properties" Medical Sciences Forum 14, no. 1: 15. https://doi.org/10.3390/ECMC2022-13268
