Discovery of potent bisindole-based pyrazolopyridine derivatives as topoisomerase inhibitors: DNA damage induction and synergistic antileukemic activity
These findings identify bis-indole and pyrazolo[3,4-<i>b</i>]pyridine derivatives, particularly compound <b>7e</b>, as potent dual topoisomerase inhibitors with significant antileukemic activity. Their ability to induce DNA damage and enhance cytotoxicity in combination with DNA damage response inhibitors highlights their potential therapeutic value, especially in combination strategies targeting replication stress pathways in leukemia.
Authors
- Ahmed T. Negmeldin (ORCID: https://orcid.org/0000-0003-3399-3435)
- Mostafa M. Elbadawi (ORCID: https://orcid.org/0000-0002-9073-4176)
- Veronika Vojáčková (ORCID: https://orcid.org/0000-0003-0946-3274)
- Miroslav Peřina (ORCID: https://orcid.org/0000-0001-5861-8688)
- Taghreed A. Majrashi (ORCID: https://orcid.org/0000-0002-0197-4275)
- Denisa Veselá (ORCID: https://orcid.org/0000-0003-2864-7087)
- Zainab M. Elsayed
- Vladimír Kryštof
- Moataz A. Shaldam
- Wagdy M. Eldehna
- Haytham O. Tawfik
- Hatem A. Abdel-Aziz
Institutions
- Kafrelsheikh University (EG)
- Cairo University (EG)
- Gulf Medical University (AE)
- Tanta University (EG)
- Palacký University Olomouc (CZ)
- King Khalid University (SA)
Publication Details
- Journal
- Frontiers in Pharmacology
- Published
- 2026-03-04
- DOI
- https://doi.org/10.3389/fphar.2026.1745220
- Primary Topic
- Cancer therapeutics and mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission