Nurhan Kishali

Synthesis and anticancer activity evaluation of new isoindole analogues

We have developed a versatile synthetic approach for the synthesis of new isoindole derivatives via the cleavage of ethers from tricyclic imide skeleton compounds. An exo-cycloadduct prepared from the Diels–Alder reaction of furan and maleic anhydride furnished imide derivatives. The epoxide ring was opened with Ac2O in the presence of a catalytic amount of H2SO4 in order to yield new isoindole derivatives (8a and 8b). The anticancer activity of these compounds was evaluated against MCF-7 (breast adenocarcinoma) and A549 (adenocarcinomic human alveolar basal epithelial) cell lines. The synthesized compounds showed concentration- and time-dependent inhibitory effects on the viability of both cell lines. Compound 8a was more toxic compared to 8b in both cancer cell lines, having higher cytotoxicity against A549 cells. Testing the toxicity properties of these compounds on the BEAS 2B (human bronchial epithelial) cell line indicated that while both compounds decreased the cell viability of cancer cells, they were less toxic on healthy lung cells. Microscopy images of A549 cells after treatment with the new isoindole derivatives displayed characteristic apoptotic morphology compared to BEAS 2B cells. The results demonstrated here suggest that these new compounds might be considered as possible potential anticancer agents for the treatment of lung and breast cancer.

Synthesis of new hexahydro-1H-isoindole-1,3(2H)-dione derivatives from 2-ethyl/phenyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3-(2H)-dione

A new and appropriate synthesis for hexahydro-1H-isoindole-1,3(2H)-dione derivatives has been developed starting from 3-sulfolene. The epoxidation of 2-ethyl/phenyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3-(2H)-dione and then the opening of the epoxide with nucleophiles gave hexahydro-1H-isoindole-1,3(2H)-dione derivatives. Amino and triazole derivatives of hexahydro-1H-isoindole-1,3(2H)-dione were synthesized from the formed product by the opening reaction of the epoxide with sodium azide. Hydroxyl analogues were obtained from cis-hydroxylation of 2-ethyl/phenyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3-(2H)-dione. The hydroxyl groups were converted to acetate.

rac-3,4-trans-Dichloro-1,2,3,4-tetra­hydro-2-naphthyl acetate

The title compound, C12H12Cl2O2, has a bicyclic skeleton containing cyclohexene and benzene fragments. The cyclohexene ring adopts a half-chair conformation with displacements of two atoms out of the least-squares plane of 0.311 (2) and −0.336 (2) Å. The Cl atoms are trans-positioned.