Synthesis, anticoagulant and PIVKA-II induced by new 4-hydroxycoumarin derivatives

Omaima M Abdelhafez; Kamelia M Amin; Rasha Z Batran; Timothy J Maher; Somaia A Nada; Shalini Sethumadhavan

doi:10.1016/j.bmc.2010.04.009

Synthesis, anticoagulant and PIVKA-II induced by new 4-hydroxycoumarin derivatives

Bioorg Med Chem. 2010 May 15;18(10):3371-8. doi: 10.1016/j.bmc.2010.04.009. Epub 2010 Apr 8.

Authors

Omaima M Abdelhafez¹, Kamelia M Amin, Rasha Z Batran, Timothy J Maher, Somaia A Nada, Shalini Sethumadhavan

Affiliation

¹ Department of Chemistry of Natural Products, National Research Center, Dokki, Cairo, Egypt. ommryan@yahoo.com

PMID: 20435480
DOI: 10.1016/j.bmc.2010.04.009

Abstract

The action of the coumarin-type drugs and related compounds is reviewed to their VKOR antagonistic effects. In our study, twenty 3-pyridinyl, pyrimidinyl and pyrazolyl-4-hydroxycoumarin derivatives were synthesized. A comparative in vivo (CT, PT determination) and in vitro (measurement of PIVKA-II levels) anticoagulant study with respect to warfarin showed that the synthesized compounds have different anticoagulant activities, the most prospective compounds were the 3-pyrazolyl-4-hydroxycoumarin derivatives.

MeSH terms

4-Hydroxycoumarins / chemistry*
4-Hydroxycoumarins / pharmacology
Administration, Oral
Anticoagulants / chemical synthesis*
Anticoagulants / pharmacology
Anticoagulants / supply & distribution
Biomarkers
Coumarins / administration & dosage
Coumarins / pharmacology
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm / drug effects
Lethal Dose 50
Molecular Structure
Platelet Aggregation Inhibitors / pharmacology*
Protein Precursors / pharmacology*
Prothrombin / pharmacology*
Structure-Activity Relationship
Warfarin / pharmacology*

Substances

4-Hydroxycoumarins
Anticoagulants
Biomarkers
Coumarins
Platelet Aggregation Inhibitors
Protein Precursors
acarboxyprothrombin
Warfarin
Prothrombin
coumarin
4-hydroxycoumarin