title: Substituted 2-hydroxy-N-(arylalkyl)benzamides induce apoptosis in cancer cell lines.
abstract: Variously substituted 2-hydroxy-N-(arylalkyl)benzamides were prepared and screened for antiproliferative and cytotoxic activity in cancer cell lines in vitro. Five compounds, out of 33 showed single-digit micromolar IC50 values against several human cancer cell lines. One of the most potent compounds N-((R)-1-(4-chlorophenylcarbamoyl)-2-phenylethyl)-5-chloro-2-hydroxybenzamide (6k) reduced proliferation and induced apoptosis in the melanoma cell line G361 in a dose-dependent manner, as shown by decrease in 5-bromo-2'-deoxyuridine incorporation and increase in several apoptotic markers, including subdiploid population increase, activation of caspases and site-specific poly-(ADP-ribose)polymerase (PARP) cleavage.
authors: Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 53210 Pardubice, Czech Republic. Electronic address: Ales.Imramovsky@upce.cz.
authors: Aleš
authors: A
authors: Imramovský
authors: Radek
authors: R
authors: Jorda
authors: Karel
authors: K
authors: Pauk
authors: Eva
authors: E
authors: Rezníčková
authors: Jan
authors: J
authors: Dušek
authors: Jiří
authors: J
authors: Hanusek
authors: Vladimír
authors: V
authors: Kryštof
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; C509928:N-(1-(4-chlorophenyl)-3-(dimethylamino)propyl)-4-phenylbenzamide; C037689:benzamide
keywords: 1-hydroxybenzotriazole hydrate; 5-bromo-2′-deoxyuridine; Apoptosis; Autophagy; B-cell lymphoma 2; B-cell lymphoma-extra large; Bcl-2; Bcl-xL; BrdU; CDK; Cancer; Cbz; Cytotoxicity; DCC; DCM; DMF; Diamides; EDC·HCl; ERK1/2; Et(2)O; Et(3)N; EtOAc; GSK; HMGB1; HOBt·H(2)O; IC(50); LC3; Mdm2; N,N′-dicyclohexylcarbodiimide; N,N′-dimethylformamide; N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride; PARP-1; PET; RT; Rb; SAR; benzyloxycarbonyl group; cyclin-dependent kinase; dichloromethane; diethylether; ethyl acetate; extracellular-signal-regulated kinases; glycogen synthase kinase; growth inhibition 50%; high-mobility group protein B1; microtubule-associated protein light chain 3; mouse double minute 2; p53; photosynthetic electron transport; poly-(ADP-ribose)polymerase-1; retinoblastoma protein; room temperature (approx. 20 °C); structure–activity relationship; triethyl amine