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Bioorg Chem. 2017 Apr;71:10-18. doi: 10.1016/j.bioorg.2017.01.008. Epub 2017 Jan 18.

Facile dimethyl amino group triggered cyclic sulfonamides synthesis and evaluation as alkaline phosphatase inhibitors.

Author information

1
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
2
Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, Lahore 54600, Pakistan.
3
Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
4
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: abdul_hameed8@hotmail.com.
5
Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan. Electronic address: drjamshed@ciit.net.pk.

Abstract

Owing to the biological importance of cyclic sulfonamides (sultams), herein we report a new, facile and cost-effective method for the synthesis of sultams that makes use of a reaction between dansyl amide and easily accessible benzaldehydes under mildly acidic conditions. All compounds were obtained in good yields (69-96%). Consequently a series of cyclic sulfonamides (7a-7n) was synthesized and characterized using FTIR, MS and NMR spectroscopy, crystal structure of compound 7b has also been determined. All compounds were evaluated for their potential to inhibit alkaline phosphatase (bTNAP and bIAP). All compounds were found to be excellent inhibitors of bTNAP with IC50 values in lower micro-molar range (0.11-6.63μM). Most of the compounds were selective inhibitors of bTNAP over bIAP. Only six compounds were found to be active against bIAP (IC50 values in the range 0.38-3.48μM). Molecular docking studies were carried out to identify and rationalize the structural elements necessary for efficient AP inhibition.

KEYWORDS:

Alkaline phosphatase inhibitors; Ectonucleotidase; Intestinal alkaline phosphatase (IAP); Sulfonamides; Sultams; Tissue non-specific alkaline phosphatase (TNAP)

PMID:
28139246
DOI:
10.1016/j.bioorg.2017.01.008
[Indexed for MEDLINE]

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