Substituted 2-hydroxy-N-(arylalkyl)benzamides induce apoptosis in cancer cell lines

  • Eur J Med Chem. 2013 Oct:68:253-9. doi: 10.1016/j.ejmech.2013.08.009.
Aleš Imramovský  1 ,  Radek Jorda ,  Karel Pauk ,  Eva Rezníčková ,  Jan Dušek ,  Jiří Hanusek ,  Vladimír Kryštof
Affiliations
  • 1. Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 53210 Pardubice, Czech Republic. Electronic address: [email protected].
PMID: 23981532 DOI: 10.1016/j.ejmech.2013.08.009
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.

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.
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