Investigation of cytotoxic properties of some isoindole-related compounds bearing silyl and azide groups with in vitro and in silico studies

This study aims to evaluate the synthesis of isoindole-1,3-dione analogues and their cytotoxic potential. A549 and HeLa cells exposed to 250–100–50–25 µM doses of each derivative were incubated for 24, 48, and 72 h. The cytotoxicity of the isoindole-1,3-dione derivatives was analyzed using the cell growth inhibition assay and the cell membrane damage test. (3aR,5R,6R,7aS)-5-Azido-2-benzyl-6-hydroxyhexahydro-1H-isoindole-1,3(2H)-dione (1d), (3aR,5R,6R,7aS)-5-azido-6-((tert-butyldiphenylsilyl)oxy)-2-ethylhexahydro-1H-isoindole-1,3(2H)-dione (2a), and (3aR,5R,6R,7aS)-5-azido-6-((tert-butyldiphenylsilyl)oxy)-2-methylhexahydro-1H-isoindole-1,3(2H)-dione (2b) compounds inhibited the growth of the A549 and HeLa cells caused membrane damage and exhibited a dose-dependent cytotoxic effect on lung and cervical carcinoma cells. The effect of tert-butyldiphenylsilyl (TBDPS) groups on cytotoxicity was observed in compounds 2a and 2b, but not in the other compounds. Considering the effect of groups attached to the nitrogen atom, the best activity was exhibited in 2b molecule to which the methyl group is attached. Additionally, the interactions of compounds (3aR,5R,6R,7aS)-5-azido-6-hydroxy-2-methylhexahydro-1H-isoindole-1,3(2H)-dione (1b), 1d, 2a and 2b with mammalian rapamycin target, human ribosomal S6 kinase 1 and human epidermal growth factor receptor were investigated by molecular docking studies,. According to the docking results, 2a and 2b compounds containing a TBDPS group have stronger binding energies than 1b and 1d compounds against all target receptors

Evaluation of isoindole derivatives: Antioxidant potential and cytotoxicity in the HT-29 colon cancer cells

Suloglu, Aysun Kilic/0000-0003-0914-1128Norcantharimides have an isoindole skeleton structure, and some isoindoline derivatives have positive effects on inflammatory pathologies, including cancers. The present study aims to evaluate the antioxidant and cytotoxic potential of four synthesized isoindoline derivatives (NCTD1-4). HT-29 cells exposed to 10, 50, 100, and 200 mu M doses of each derivative were incubated for 24 and 48 h, respectively. The cytotoxicity of the new derivatives was analyzed using the cell growth inhibition assay and the cell membrane damage test. In vitro antioxidant activity studies showed that the derivatives have free radical-scavenging effects in a dose-dependent manner. NCTD3 and NCTD4 apparently have antioxidant effects when compared with the control group treated with dimethyl sulfoxide. Furthermore, NCTD4 inhibited the growth of the HT-29 cells due to membrane damage and exhibited a dose-dependent cytotoxic effect on colon adenocarcinoma cells. The findings suggest that NDTD4 has the highest potential for colon cancer treatment and may be interpreted as a candidate anticancer agent.Hacettepe University Scientific Research Project UnitHacettepe University [014 D07 301 002-664]This study was supported by Hacettepe University Scientific Research Project Unit (Project Number: 014 D07 301 002-664)

Evaluation of isoindole derivatives: Antioxidant potential and cytotoxicity in the HT‐29 colon cancer cells

Suloglu, Aysun Kilic/0000-0003-0914-1128Norcantharimides have an isoindole skeleton structure, and some isoindoline derivatives have positive effects on inflammatory pathologies, including cancers. The present study aims to evaluate the antioxidant and cytotoxic potential of four synthesized isoindoline derivatives (NCTD1-4). HT-29 cells exposed to 10, 50, 100, and 200 mu M doses of each derivative were incubated for 24 and 48 h, respectively. The cytotoxicity of the new derivatives was analyzed using the cell growth inhibition assay and the cell membrane damage test. In vitro antioxidant activity studies showed that the derivatives have free radical-scavenging effects in a dose-dependent manner. NCTD3 and NCTD4 apparently have antioxidant effects when compared with the control group treated with dimethyl sulfoxide. Furthermore, NCTD4 inhibited the growth of the HT-29 cells due to membrane damage and exhibited a dose-dependent cytotoxic effect on colon adenocarcinoma cells. The findings suggest that NDTD4 has the highest potential for colon cancer treatment and may be interpreted as a candidate anticancer agent.Hacettepe University Scientific Research Project UnitHacettepe University [014 D07 301 002-664]This study was supported by Hacettepe University Scientific Research Project Unit (Project Number: 014 D07 301 002-664)