Topoisomerase II inhibitors design: Early studies and new perspectives

Hadeer K Swedan; Asmaa E Kassab; Ehab M Gedawy; Salwa E Elmeligie

doi:10.1016/j.bioorg.2023.106548

Topoisomerase II inhibitors design: Early studies and new perspectives

Bioorg Chem. 2023 Jul:136:106548. doi: 10.1016/j.bioorg.2023.106548. Epub 2023 Apr 20.

Authors

Hadeer K Swedan¹, Asmaa E Kassab², Ehab M Gedawy³, Salwa E Elmeligie⁴

Affiliations

¹ Central Administration of Research and Health Development, Ministry of Health, and Population (MoHP), Cairo P.O. Box 11516, Egypt.
² Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo P.O. Box 11562, Egypt. Electronic address: asmaa.kassab@pharma.cu.edu.eg.
³ Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo P.O. Box 11562, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Industries, Badr University in Cairo (BUC), Badr City, Cairo P.O. Box 11829, Egypt.
⁴ Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo P.O. Box 11562, Egypt.

PMID: 37094479
DOI: 10.1016/j.bioorg.2023.106548

Abstract

The DNA topoisomerase enzymes are widely distributed throughout all spheres of life and are necessary for cell function. Numerous antibacterial and cancer chemotherapeutic drugs target the various topoisomerase enzymes because of their roles in maintaining DNA topology during DNA replication and transcription. Agents derived from natural products, like anthracyclines, epipodophyllotoxins and quinolones, have been widely used to treat a variety of cancers. A very active field of fundamental and clinical research is the selective targeting of topoisomerase II enzymes for cancer treatment. This thematic review summarizes the recent advances in the anticancer activity of the most potent topoisomerase II inhibitors (anthracyclines, epipodophyllotoxins and fluoroquinolones) their modes of action, and structure-activity relationships (SARs) organized chronologically in the last ten years from 2013 to 2023. The review also highlights the mechanism of action and SARs of promising new topoisomerase II inhibitors.

Keywords: Anthracyclines; Anticancer; Epipodophyllotoxins; Fluoroquinolones; Mechanism of action; SAR; Topoisomerase II.

Publication types

Review

MeSH terms

Anthracyclines
Antibiotics, Antineoplastic / pharmacology
Antineoplastic Agents* / pharmacology
DNA Topoisomerases, Type II
Podophyllotoxin
Topoisomerase I Inhibitors
Topoisomerase II Inhibitors* / pharmacology

Substances

Topoisomerase II Inhibitors
Antineoplastic Agents
Antibiotics, Antineoplastic
DNA Topoisomerases, Type II
Podophyllotoxin
Anthracyclines
Topoisomerase I Inhibitors