Evaluation of Cytotoxic Potentials of Some Isoindole-1, 3-Dione Derivatives on HeLa, C6 and A549 Cancer Cell Lines

Author(s): Ayse Tan, Ayse Sahin Yaglioglu, Nurhan Horasan Kishali*, Ertan Sahin, Yunus Kara*.

Journal Name: Medicinal Chemistry

Volume 16 , Issue 1 , 2020

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Graphical Abstract:


Background: Norcantharimides are known as norcantharidine derivatives and contain an isoindole skeleton structure. Isoindole derivatives have positive effect on inflammatory pathologies including cancers.

Objective: Considering this information, firstly, isoindole derivatives containing different functional groups 4-13 have been synthesized from 2-alkyl/aryl-3a, 4,7,7a-tetrahydro-1H-isoindole-1, 3(2H)-dione.

Methods: For the synthesis of all compounds, 2-alkyl/aryl-3a, 4,7,7a-tetrahydro-1H-isoindole- 1,3(2H)-dione was used as the starting compound. The syntheses were based on two main reactions: Ene-reaction of singlet oxygen and epoxidation. Secondly, their anticancer activities were evaluated against HeLa, C6 and A549 cancer cell lines by the BrdU assay.

Results: Anticancer activities of synthesized compounds (4-13) and 5-FU (5-Florouracil) against HeLa, C6 and A549 cells were investigated at four concentrations (100, 50, 25 and 5 μM). IC50 values of compounds 4-13 were calculated for all cancer cell lines. The investigated compounds showed anticancer activity against the cancer cell lines depending on doses. Compound 7 containing azide and silyl ether exhibited higher inhibitory activity than the other compounds and 5-FU against A549 cancer cell lines (IC50 =19.41± 0.01 μM). Compounds 9 and 11 were determined to exhibit cell-selective activity against HeLa cancer cell lines. Compound 11 had higher activity than the positive control at 100 μM concentrations against C6 cancer cell lines.

Conclusion: According to the results observed, isoindole derivatives 7, 9, and 11 might be good potential anticancer agents for the treatment of cervical and glioma cancer due to their antiproliferative properties, having less cytotoxic effects on healthy cells. In addition, compound 7 could be used in in vivo studies of all three-cancer cell lines (C6, HeLa, and A549).

Keywords: Isoindoline-1, 3-dione, norcantharimide, anticancer activity, heLa cells, C6 cells, 5-fluorouracil, A549 cells.

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Year: 2020
Page: [69 - 77]
Pages: 9
DOI: 10.2174/1573406415666181206115638
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