Design, synthesis and biological evaluation of novel pyridine-thiazolidinone derivatives as anticancer agents: Targeting human carbonic anhydrase IX.

Abstract:

:In order to obtain novel Human carbonic anhydrase IX (CAIX) inhibitors, a series of pyridine-thiazolidinone derivatives was synthesized and characterized by various spectroscopic techniques. The binding affinity of the compounds was measured by fluorescence binding studies and enzyme inhibition activity using esterase assay of CAIX. It was observed that compound 8 and 11 significantly inhibit the CAIX activity with the IC50 value, 1.61 μM and 1.84 μM, respectively. The binding-affinity of compound 8 and 11 for CAIX was significantly high with their KD values 11.21 μM and 2.32 μM, respectively. Docking studies revealed that compound 8 and 11 efficiently binds in the active site cavity of CA IX by forming sufficient numbers of H-bonds and van der Waals interactions with active side residues. All the compounds were further screened in vitro for anticancer activity and found that compound 8 and 11 exhibit considerable anticancer activity against MCF-7 and HepG-2 cell lines. All these findings suggest that compound 8 and 11 may be further exploited as a novel pharmacophore model for the development of anticancer agents.

journal_name

Eur J Med Chem

authors

Ansari MF,Idrees D,Hassan MI,Ahmad K,Avecilla F,Azam A

doi

10.1016/j.ejmech.2017.12.049

subject

Has Abstract

pub_date

2018-01-20 00:00:00

pages

544-556

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(17)31081-4

journal_volume

144

pub_type

杂志文章