HDAC and NF-κB mediated cytotoxicity induced by novel N-Chloro β-lactams and benzisoxazole derivatives

Chemico-biological Interactions
C B Rajashekar ReddyArumugam Sivakumar

Abstract

Novel N-chloro â-Lactam and benzisoxazole derivatives were successfully synthesized with excellent yields (92-96%) under simple and mild reaction conditions. The β-lactams as a class acquired importance since the discovery of penicillin which contains β-lactam unit as an essential structural feature of its molecule, this interest continued unabated because of the therapeutic importance of β-lactam antibiotics. In silico studies of the compounds with cancer drug target enzymes showed the inhibition of HDAC (Histone Deacetylase) and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) significantly. The compounds were then investigated for the inhibitory potential against the same enzymes in vitro. NF-κB inhibition was investigated by trans activation assay using HEK293/NF-κB-luc cells. Overall, the synthesized compounds induce the cancer cell toxicity by restraining the NF-κB transcription factor mediated by HDAC inhibition and thus the compounds act as dual inhibitors.

References

Jul 1, 1968·Journal of Pharmaceutical Sciences·T Kondo, M Tomizawa
May 23, 1998·Annual Review of Immunology·S GhoshE B Kopp
May 5, 1999·Chemico-biological Interactions·M A VivesM P Vinardell
Aug 27, 1999·Biochemical and Biophysical Research Communications·H R Wong, I Y Menendez
Jun 3, 2000·Annual Review of Immunology·M Karin, Y Ben-Neriah
Aug 3, 2000·Journal of the National Cancer Institute·P A MarksR A Rifkind
Jan 3, 2001·The Journal of Clinical Investigation·P P Tak, G S Firestein
May 10, 2002·The Journal of Pharmacy and Pharmacology·Paul Bremner, Michael Heinrich
Dec 4, 2003·Journal of Medicinal Chemistry·Monish Jain, Chul-Hoon Kwon
Apr 12, 2005·Annual Review of Pharmacology and Toxicology·Daryl C DrummondChristopher C Benz
May 24, 2005·Apoptosis : an International Journal on Programmed Cell Death·F HabensG Packham
Aug 22, 2006·Mini Reviews in Medicinal Chemistry·Nguyen-Hai Nam
Oct 4, 2006·Nature Reviews. Drug Discovery·Peter ImmingAchim Meyer
Apr 6, 2007·Biological & Pharmaceutical Bulletin·WenYi JinKiHwan Bae
May 15, 2007·Biochemical Pharmacology·Keith B Glaser
Oct 24, 2007·Molecular Cancer Research : MCR·Milos DokmanovicPaul A Marks
Dec 20, 2007·Journal of Natural Products·Florence FolmerMarc Diederich
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
Jan 25, 2011·Bioorganic & Medicinal Chemistry Letters·Eunhyun ChoiGyoonhee Han
Jun 8, 2012·Evidence-based Complementary and Alternative Medicine : ECAM·E RozemaB Kopp
Aug 7, 2013·Molecular Cancer·Bastian Hoesel, Johannes A Schmid

❮ Previous
Next ❯

Citations

Jan 29, 2019·Current Topics in Medicinal Chemistry·Yu BaiGuihua Cui
Mar 10, 2020·Current Topics in Medicinal Chemistry·Xinfen Zhang, Yanshu Jia

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

B-Cell Leukemia (Keystone)

B-cell leukemia includes various types of lymphoid leukemia that affect B cells. Here is the latest research on B-cell leukemia.

© 2022 Meta ULC. All rights reserved