Pharmacokinetics-pharmacodynamics and antitumor activity of mercaptoacetamide-based histone deacetylase inhibitors.

ABSTRACT: Structurally diverse histone deacetylase inhibitors (HDACI) have emerged as chemotherapeutic agents. Here, we report the first mercaptoacetamide HDACIs (coded 6MAQH and 5MABMA) for use in treatment against prostate cancer cells in vitro and in vivo and correlate their plasma pharmacokinetics and tissue-pharmacodynamics with tumor sensitivity. HDACIs were assessed for in vitro microsomal stability and growth inhibition against prostate cancer and nonmalignant cells. Antitumor activity was determined following i.p. administration of 6MAQH and 5MABMA (0.5 and 5 mg/Kg) using mice bearing PC3 tumor xenografts (n = 10). The plasma pharmacokinetics of 6MAQH and 5MABMA and their effects on the acetylation of histone H4 in tissues were determined in athymic mice. Both HDACIs significantly inhibited

SUBMITTER: Konsoula Z 

PROVIDER: S-EPMC3711100 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature