149648-52-2Relevant articles and documents
Platinum(IV) prodrugs multiply targeting genomic DNA, histone deacetylases and PARP-1
Xu, Zichen,Hu, Weiwei,Wang, Zhimei,Gou, Shaohua
, p. 211 - 220 (2017)
Several Pt(IV) prodrugs containing SAA, a histone deacetylases inhibitor, were designed and prepared for multiply targeting genomic DNA, histone deacetylases and PARP-1. The resulting Pt(IV) prodrug had significantly strong antiproliferative activity against the tested cancer cell lines, especially SAA1, derived from the conjugation of cisplatin and SAA, had potent ability to overcome cisplatin resistance. Under the combined action of DNA platination and inhibition of HDACs and PARP-1 activity, the cytotoxic activity of SAA1 was 174-fold higher than cisplatin against cisplatin-resistant SGC7901/CDDP cancer cells. The mechanism of action of SAA1 was preliminarily investigated, in which cellular uptake, cell apoptosis and cell cycle arrest as well as western blot analysis were made by treating SAA1 with SGC7901/CDDP cells. Besides, HDACs inhibition activity and PARP-1 enzyme inhibition of SAA1 were also studied.
Histone Deacetylase 2 (HDAC2) Inhibitors Containing Boron
Kavianpour, Poya,Gemmell, Madeleine C. M.,Kahlert, Jan U.,Rendina, Louis M.
, p. 2786 - 2791 (2020/06/25)
Histone deacetylase enzymes (HDACs) are responsible for the global silencing of tumour-suppressor genes. Treatment with a histone deacetylase inhibitor (HDACi) can reverse this process and restore normal cell function. Herein, we report a small series of boron-based (boronic acid, boronate ester and closo-1,2-carborane) HDAC2 inhibitors with IC50 values in the nanomolar range. The boronate ester 4 b was the most potent compound assessed in this study (IC50=40.6±1.5 nM), followed closely by the 1,2-closo-carborane (IC50=42.9±1.5 nM). Compound 4 b exceeds the potency of the related gold-standard HDAC pan-inhibitor vorinostat (1) toward this particular HDAC isoform.
H2O2/Peroxynitrite-Activated Hydroxamic Acid HDAC Inhibitor Prodrugs Show Antileukemic Activities against AML Cells
Liao, Yi,Xu, Liping,Ou, Siyu,Edwards, Holly,Luedtke, Daniel,Ge, Yubin,Qin, Zhihui
supporting information, p. 635 - 640 (2018/06/22)
Occurrence of acute myeloid leukemia (AML) results in abundant endogenous reactive oxygen species (ROS)/reactive nitrogen species (RNS) in AML cells and in disease-relevant microenvironments. Histone deacetylase inhibitor (HDACi) prodrug approach was designed accordingly by masking the hydroxamic acid zinc binding group with hydrogen peroxide (H2O2)/peroxynitrite (PNT)-sensitive, self-immolative aryl boronic acid moiety. Model prodrugs 5-82 and 5-23 were activated in AML cells to release cytotoxic HDACis, evidenced by inducing acetylation markers and reducing viability of AML cells. Intracellular activation and antileukemic activities of prodrug were increased or decreased by ROS/PNT inducers and scavengers, respectively. Prodrugs 5-82 and 5-23 also enhanced the potency of chemotherapy drug cytarabine, supporting the potentials of this prodrug class in combinatorial treatment.