title: Cytotoxic activity assessment, QSAR and docking study of novel bis-carboxamide derivatives of 4-pyrones synthesized by Ugi four-component reaction.
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.
authors.affiliation: Department of Organic Chemistry and Biochemistry, Faculty of Chemistry, University of Tabriz, Tabriz 5166614766, Iran. ashahrisa@yahoo.com
authors.forename: Aziz
authors.initials: A
authors.lastname: Shahrisa
authors.forename: Somayeh
authors.initials: S
authors.lastname: Esmati
authors.forename: Ramin
authors.initials: R
authors.lastname: Miri
authors.forename: Omidreza
authors.initials: O
authors.lastname: Firuzi
authors.forename: Najmeh
authors.initials: N
authors.lastname: Edraki
authors.forename: Maryam
authors.initials: M
authors.lastname: Nejati
mesh_terms: D000577:Amides / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D019061:src-Family Kinases / Q000737:chemistry / Q000378:metabolism
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D011753:Pyrones; D019061:src-Family Kinases
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