Design, synthesis and biological evaluation of trinary benzocoumarin-thiazoles-azomethines derivatives as effective and selective inhibitors of alkaline phosphatase

Pervaiz Ali Channar; Hina Irum; Abid Mahmood; Ghulam Shabir; Sumera Zaib; Aamer Saeed; Zaman Ashraf; Fayaz Ali Larik; Joanna Lecka; Jean Sévigny; Jamshed Iqbal

doi:10.1016/j.bioorg.2019.103137

Design, synthesis and biological evaluation of trinary benzocoumarin-thiazoles-azomethines derivatives as effective and selective inhibitors of alkaline phosphatase

Bioorg Chem. 2019 Oct:91:103137. doi: 10.1016/j.bioorg.2019.103137. Epub 2019 Jul 23.

Authors

Affiliations

¹ Department of Chemistry, Quaid-i-Azam University, 45320 Islamabad, Pakistan.
² Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan.
³ Department of Chemistry, Quaid-i-Azam University, 45320 Islamabad, Pakistan. Electronic address: asaeed@qau.edu.pk.
⁴ Department of Chemistry, Allama Iqbal Open University, Islamabad, Pakistan.
⁵ Département de microbiologie-infectiologie et d'immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, Canada; Centre de Recherche du CHU de Québec - Université Laval, Québec, QC G1V 4G2, Canada.
⁶ Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan. Electronic address: drjamshed@cuiatd.edu.pk.

PMID: 31400554
DOI: 10.1016/j.bioorg.2019.103137

Abstract

Design, synthesis and characterization of new trinary Benzocoumarin-Thiazoles-Azomethine derivatives having three bioactive scaffolds in a single structural unit were carried out. The newly synthesized molecules were investigated for the inhibitory activity on human tissue nonspecific alkaline phosphatase (h-TNAP) and human intestinal alkaline phosphatase (h-IAP) isozymes. All the tested compounds exhibited the potent inhibition profile on both isozymes of alkaline phosphatase i.e., h-TNAP and h-IAP. Molecular docking studies were performed to explore the putative binding mode of interactions of selective inhibitors. Moreover, the synthesized derivatives were evaluated against cervical cancer cell line, HeLa and a few compounds exhibited significant inhibition in the range of 21.0-69.7%. The derivatives can be potential and selective alkaline phosphatase inhibitors for future studies.

Keywords: Anticancer; Azomethine; Coumarin; Design; Human intestinal alkaline phosphatase; Synthesis; Thiazole; Tissue-nonspecific alkaline phosphatase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkaline Phosphatase / antagonists & inhibitors*
Alkaline Phosphatase / chemistry
Alkaline Phosphatase / metabolism
Animals
COS Cells
Catalytic Domain
Cell Line, Tumor
Cell Proliferation / drug effects
Chlorocebus aethiops
Coumarins / chemical synthesis
Coumarins / metabolism
Coumarins / pharmacology*
Drug Design
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / metabolism
Enzyme Inhibitors / pharmacology*
GPI-Linked Proteins / antagonists & inhibitors
GPI-Linked Proteins / chemistry
GPI-Linked Proteins / metabolism
Humans
Hydrazones / chemical synthesis
Hydrazones / metabolism
Hydrazones / pharmacology*
Molecular Docking Simulation
Molecular Structure
Protein Binding
Structure-Activity Relationship
Thiazoles / chemical synthesis
Thiazoles / metabolism
Thiazoles / pharmacology*

Substances

Coumarins
Enzyme Inhibitors
GPI-Linked Proteins
Hydrazones
Thiazoles
ALPI protein, human
Alkaline Phosphatase