Universität zu Köln

Goehringer, Nils, Peng, Yayi, Nitzsche, Bianca, Biermann, Hannah, Pradhan, Rohan, Schobert, Rainer, Herling, Marco, Hoepfner, Michael and Biersack, Bernhard ORCID: 0000-0001-7305-346X (2021). Improved Anticancer Activities of a New Pentafluorothio-Substituted Vorinostat-Type Histone Deacetylase Inhibitor. Pharmaceuticals, 14 (12). BASEL: MDPI. ISSN 1424-8247

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Abstract

The development of new anticancer drugs is necessary in order deal with the disease and with the drawbacks of currently applied drugs. Epigenetic dysregulations are a central hallmark of cancerogenesis and histone deacetylases (HDACs) emerged as promising anticancer targets. HDAC inhibitors are promising epigenetic anticancer drugs and new HDAC inhibitors are sought for in order to obtain potent drug candidates. The new HDAC inhibitor SF5-SAHA was synthesized and analyzed for its anticancer properties. The new compound SF5-SAHA showed strong inhibition of tumor cell growth with IC50 values similar to or lower than that of the clinically applied reference compound vorinostat/SAHA (suberoylanilide hydroxamic acid). Target specific HDAC inhibition was demonstrated by Western blot analyses. Unspecific cytotoxic effects were not observed in LDH-release measurements. Pro-apoptotic formation of reactive oxygen species (ROS) and caspase-3 activity induction in prostate carcinoma and hepatocellular carcinoma cell lines DU145 and Hep-G2 seem to be further aspects of the mode of action. Antiangiogenic activity of SF5-SAHA was observed on chorioallantoic membranes of fertilized chicken eggs (CAM assay). The presence of the pentafluorothio-substituent of SF5-SAHA increased the antiproliferative effects in both solid tumor and leukemia/lymphoma cell models when compared with its parent compound vorinostat. Based on this preliminary study, SF5-SAHA has the prerequisites to be further developed as a new HDAC inhibitory anticancer drug candidate.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Goehringer, Nils UNSPECIFIED UNSPECIFIED UNSPECIFIED Peng, Yayi UNSPECIFIED UNSPECIFIED UNSPECIFIED Nitzsche, Bianca UNSPECIFIED UNSPECIFIED UNSPECIFIED Biermann, Hannah UNSPECIFIED UNSPECIFIED UNSPECIFIED Pradhan, Rohan UNSPECIFIED UNSPECIFIED UNSPECIFIED Schobert, Rainer UNSPECIFIED UNSPECIFIED UNSPECIFIED Herling, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoepfner, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Biersack, Bernhard UNSPECIFIED orcid.org/0000-0001-7305-346X UNSPECIFIED
URN:	urn:nbn:de:hbz:38-589782
DOI:	10.3390/ph14121319
Journal or Publication Title:	Pharmaceuticals
Volume:	14
Number:	12
Date:	2021
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1424-8247
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROSTATE-CANCER; POLY(ADP-RIBOSE) POLYMERASE; HEPATOCELLULAR-CARCINOMA; HDAC INHIBITOR; APOPTOSIS; CELLS; EXPRESSION; CLEAVAGE; OVEREXPRESSION; RIDAFOROLIMUS Multiple languages Chemistry, Medicinal; Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58978