Cytotoxic activity assessment, QSAR and docking study of novel bis-carboxamide derivatives of 4-pyrones synthesized by Ugi four-component reaction

  • Eur J Med Chem. 2013 Aug:66:388-99. doi: 10.1016/j.ejmech.2013.05.049.
Aziz Shahrisa  1 ,  Somayeh Esmati ,  Ramin Miri ,  Omidreza Firuzi ,  Najmeh Edraki ,  Maryam Nejati
Affiliations
  • 1. Department of Organic Chemistry and Biochemistry, Faculty of Chemistry, University of Tabriz, Tabriz 5166614766, Iran. [email protected]
PMID: 23827179 DOI: 10.1016/j.ejmech.2013.05.049
Abstract

Fourteen novel bis-carboxamide derivatives of 4-pyrones were designed and synthesized via Ugi four-component reactions of 4-pyrone carbaldehydes, aromatic amines, isocyanides and carboxylic acids. The cytotoxic activity of synthesized derivatives was evaluated against LS180, MCF-7 and HL-60 cell lines using MTT reduction assay. Synthesized compounds demonstrated strong cytotoxic potential in HL-60 cell line. Compound 12n was the most potent derivative with IC50 values of 16.1, 9.1 and 13.8 μM in LS180, MCF-7 and HL-60 cells, respectively. The results of MLR-QSAR study indicated that topological property of these derivatives directly influenced the cytotoxic potential in HL-60 cell line. Docking study of compounds, conducted for ATP binding site of Src tyrosine kinase, demonstrated the key H-bond interaction with Met 347 of the hinge region.

Keywords
4-Pyrone derivatives; BDARYDWRHWUSIM-UHFFFAOYSA-N; CDBRCRNQCXUTIV-UHFFFAOYSA-N; CLEXFLYJVCLTOA-UHFFFAOYSA-N; Docking; GUTWJZUTKAWCGG-UHFFFAOYSA-N; JNQYYKJZNNMTRC-UHFFFAOYSA-N; KVXLAPJDNHTDAZ-UHFFFAOYSA-N; KWSCKMBQSBXXEI-UHFFFAOYSA-N; LELHAJLPSUSZDJ-UHFFFAOYSA-N; NKAMEMUWKVEKDI-UHFFFAOYSA-N; OUBASOSEZSZVPK-UHFFFAOYSA-N; QSAR; RGLLSWIFVPBSGB-UHFFFAOYSA-N; Src tyrosine kinase; UWUSAIANTFFXIK-UHFFFAOYSA-N; Ugi reaction; ZAVJAAMISZEVET-UHFFFAOYSA-N; ZIRLIAJWTWDNHC-UHFFFAOYSA-N.