ArticleInternational journal of molecular sciences2020
In Vitro Assessment of the Genotoxic Hazard of Novel Hydroxamic Acid- and Benzamide-Type Histone Deacetylase Inhibitors (HDACi).
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Fair and Square: Design, Synthesis and Biological Evaluations of Squaric Acid Derivatives as Novel HDAC8 Inhibitors.ChemMedChem · 2026Article
- Overcoming acquired doxorubicin resistance of ovarian carcinoma cells by verapamil‑mediated promotion of DNA damage‑driven cytotoxicity.International journal of oncology · 2026Article
- VUScope: a mathematical model for evaluating image-based drug response measurements and predicting long-term incubation outcomes.Bioinformatics (Oxford, England) · 2026Article
- Recent progress in synthetic strategies to develop potent, HDAC8-selective, small-molecule inhibitors.Bioorganic & medicinal chemistry letters · 2025Review
- Substrate-Guided Development of HDAC11-Selective Inhibitors Featuring α‑Amino Amide Zinc-Binding Groups.ACS omega · 2025Article
- Monothiooxalamide-Benzothiazole Hybrids: Predictive Docking on HDAC6, Synthesis, Molecular Structure, and Antiproliferative Activity on Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Article
- Drug Discovery for Histone Deacetylase Inhibition: Past, Present and Future of Zinc-Binding Groups.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Computationally Guided Design, Synthesis, and Evaluation of Novel Non-Hydroxamic Histone Deacetylase Inhibitors, Based onPharmaceuticals (Basel, Switzerland) · 2025Article
- Article
- Anticancer Therapy with HDAC Inhibitors: Mechanism-Based Combination Strategies and Future Perspectives.Cancers · 2021Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Histone deacetylase inhibitors (HDACi) are already approved for the therapy of leukemias. Since they are also emerging candidate compounds for the treatment of non-malignant diseases, HDACi with a wide therapeutic window and low hazard potential are desirable. Here, we investigated a panel of 12 novel hydroxamic acid- and benzamide-type HDACi employing non-malignant V79 hamster cells as toxicology guideline-conform in vitro model. HDACi causing a ≥10-fold preferential cytotoxicity in malignant neuroblastoma over non-malignant V79 cells were selected for further genotoxic hazard analysis, including vorinostat and entinostat for control. All HDACi selected, (i.e., KSK64, TOK77, DDK137 and MPK77) were clastogenic and evoked DNA strand breaks in non-malignant V79 cells as demonstrated by micronucleus and comet assays, histone H2AX foci formation analyses (γH2AX), DNA damage response (DDR) assays as well as employing DNA double-strand break (DSB) repair-defective VC8 hamster cells. Genetic instability induced by hydroxamic acid-type HDACi seems to be independent of bulky DNA adduct formation as concluded from the analysis of nucleotide excision repair (NER) deficient mutants. Summarizing, KSK64 revealed the highest genotoxic hazard and DDR stimulating potential, while TOK77 and MPK77 showed the lowest DNA damaging capacity. Therefore, these compounds are suggested as the most promising novel candidate HDACi for subsequent pre-clinical in vivo studies.
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Registered trials
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