235098-07-4Relevant academic research and scientific papers
Synthesis and antitumor activity of certain new substituted 1H- isoindoldione derivatives
Al-Obaid,El-Shafie,Al-Mutairi,El-Subbagh
, p. 129 - 147 (2007/10/03)
A series of new 1H-isoindol-1,3-dione analogs bearing either methyl or phenyl groups at positions 6 and 7, 4-amino and 5-cyano functions and fitted with either 2-hydroxy, 2-substituted amino, 2-sulfonyloxy, 2-sulfonamido, 2- substituted amido, 2-thioureido or 2-substituted arylazomethine moieties has been synthesized. Structural elucidation of the newly synthesized compounds was achieved based on elementary analysis, 1H and 13C NMR and Mass spectra. The antitumor screening of the prepared compounds was performed at the National Cancer Institute (NCI) Bethesda, Maryland, USA. The 1H-isoindol- 1,3-dione analogs showed a distinctive potential pattern of selectivity as well as broad spectrum antitumor activity. Compound 4-amino-5-cyano-6,7- dimethyl-2-(benzenesulfonyloxy)1H-isoindol-1,3-dione (16) showed a remarkable activity against HCT-116 colon cancer and T-47 breast cancer with GI50 values of 4.4 and 2.6 μM, respectively, while compound 4-amino-5-cyano-6,7- diphenyl-2-(4-methylbenzenesulfonyloxy)-1H-isoindol-1,3-dione (20) proved to be active against MOLT-4 and SR leukemia cells as well as the renal cancer cells RXF 393, with GI50 values of 10.2, 8.4 and 10.4 μM, respectively. Meanwhile, compound 16 showed a broad spectrum antitumor activity against 60 different tumor cell lines with GI50, TGI and LC50 (MG-MID) values of 25.3, 58.8 and 91.4 μM, respectively, while compound 20 showed GI50, TGI and LC50 (MG-MID) values of 17.3, 46.0 and 79.6 μM, respectively. The detailed synthesis and biological screening data are reported.
