Synthesis, characterization and biological evaluation of tertiary sulfonamide derivatives of pyridyl-indole based heteroaryl chalcone as potential carbonic anhydrase IX inhibitors and anticancer agents

Mudasir Nabi Peerzada; Parvez Khan; Kamal Ahmad; Md Imtaiyaz Hassan; Amir Azam

doi:10.1016/j.ejmech.2018.05.034

Synthesis, characterization and biological evaluation of tertiary sulfonamide derivatives of pyridyl-indole based heteroaryl chalcone as potential carbonic anhydrase IX inhibitors and anticancer agents

Eur J Med Chem. 2018 Jul 15:155:13-23. doi: 10.1016/j.ejmech.2018.05.034. Epub 2018 May 22.

Authors

Mudasir Nabi Peerzada¹, Parvez Khan², Kamal Ahmad², Md Imtaiyaz Hassan², Amir Azam³

Affiliations

¹ Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, 110 025, New Delhi, India.
² Centre for Interdisciplinary Research in Basic Science, Jamia Nagar, 110 025, New Delhi, India.
³ Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, 110 025, New Delhi, India. Electronic address: amir_sumbul@yahoo.co.in.

PMID: 29852328
DOI: 10.1016/j.ejmech.2018.05.034

Abstract

In the quest for novel effective carbonic anhydrase inhibitors, some sulfonamide derivatives of pyridyl-indole based chalcone were synthesized and screened in vitro for inhibitory activity against human carbonic anhydrase IX isoform. Among all the synthesized compounds (SC2 -SC11), only three compounds SC3, SC7 and SC10 were found to have better binding affinity as shown by molecular docking and fluorescence binding studies. Further, the enzyme inhibition assay and in vitro anti-tumor evaluation against MCF-7 and HepG-2 cell lines revealed that the compounds SC3, SC7 and SC10 inhibited the CA IX selectively, possessed predominant anti-proliferative potential and significantly induced apoptosis in cancerous cells.

Keywords: Apoptosis; Carbonic anhydrase inhibition; Chalcone; Molecular docking; Tertiary sulfonamide.

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Carbonic Anhydrase IX / antagonists & inhibitors*
Carbonic Anhydrase IX / metabolism
Carbonic Anhydrase Inhibitors / chemical synthesis
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Chalcone / chemistry
Chalcone / pharmacology*
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
HEK293 Cells
Humans
Indoles / chemistry
Indoles / pharmacology*
Molecular Docking Simulation
Molecular Structure
Pyridines / chemistry
Pyridines / pharmacology*
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry
Sulfonamides / pharmacology*

Substances

Antineoplastic Agents
Carbonic Anhydrase Inhibitors
Indoles
Pyridines
Sulfonamides
Chalcone
indole
Carbonic Anhydrase IX