title: Naphthalene-fused (α-alkoxycarbonyl)methylene-γ-butyrolactones: antiproliferative activity and binding to bovine serum albumin and DNA.
abstract: A naphthalene-fused (α-alkoxycarbonyl)methylene-γ-butyrolactone (methyl 2-[7-hydroxy-2-oxonaphtho[1,2-b]furan-3(2H)-yliden]acetate) has been prepared as a representative compound of a potential class of cytotoxic agents. In vitro cytotoxicity has been evaluated against HCT-15 colon and MCF-7 breast cancer cells and IC(50) was 64-66 μM, causing morphological changes in cells, such as loss of adhesion, rounding, cell shrinkage, and detachment from the substratum. The binding constant K of the complex between the naphthyl lactone with bovine serum albumin (8 × 10(3) M(-1)) suggests a minor change in protein folding. The K of the binding with DNA (1.06 × 10(4) M(-1)) suggests nonspecific electrostatic interactions with DNA and this was confirmed by melting point data (Tm<0.6 °C). Therefore, naphthalene-fused (α-alkoxycarbonyl)methylene-γ-butyrolactone should not be able to intercalate with DNA but its interaction should occur at the level of DNA surface.
authors.affiliation: Department of Chemistry and Biochemistry, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran. m.rajabi.s@gmail.com
authors.forename: Mehdi
authors.initials: M
authors.lastname: Rajabi
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Khalilzadeh
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Tavakolinia
authors.forename: Paola
authors.initials: P
authors.lastname: Signorelli
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ghidoni
authors.forename: Enzo
authors.initials: E
authors.lastname: Santaniello
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D005260:Female; D006801:Humans; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry*; D009284:Naphthols / Q000138:chemical synthesis / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D009281:Naphthalenes; D009284:Naphthols; C573736:methyl 2-(7-hydroxy-2-oxonaphtho(1,2-b)furan-3(2H)-yliden)acetate; C031721:naphthalene; D012710:Serum Albumin, Bovine; D004247:DNA; D015107:4-Butyrolactone