Purpose: Screening of new 3,3'-((5,5'-(Ethane-1,2-diyl)bis(3-mercapto-4H-1,2,4-triazole-5,4-diyl))bis(azanylylidene))bis(substituted indolin-2-one) derivatives as DNA intercalators for in vitro anticancer activity.
Fifteen new 3,3'-((5,5'-(Ethane-1,2-diyl)bis(3-mercapto-4H-1,2,4-triazole-5,4-diyl))bis(azanylylidene))bis(substituted indolin-2-one) derivatives were screened for in vitro anticancer activity by MTT assay method using Doxorubicin as standard drug. DNA binding studies were also conducted by standard protocol available in literature.
All the compounds were subjected for in vitro anticancer activity against MCF-7 (breast cancer), A549 (lung cancer) and HEPG2 (liver cancer) cell lines using MTT assay method. Among the three cell lines, the newly synthesized compounds showed good anticancer activity against HEPG2cell lines. The compounds with( R2 = 5,7-dibromo) and (R2 = 5-chloro) exhibited potent anticancer activity with IC50 values 1.8 μM and 6.50 μM against HEPG2 cell lines. Compounds with (R2 = 5- fluoro), (R2 = 5-bromo) and (R1 = 1-acetyl, R2 = 5-bromo) with IC50 values 10.62 μM, 11.61 μM and 12.61 μM exhibited moderate anticancer activity respectively against HEPG2 cell lines. Compound (R2 = 5,7-dibromo) was found to be potent against MCF-7 cell lines with IC50 values 2.3 μM and the compound with (5-fluoro) was next in the order of anticancer activity with IC50 value 10.32 μM. All the remaining compounds showed mild to moderate activity against all the three cell lines. Some of the compounds with (R2 = 7-carboxy) and (R1 = 1-acetyl) did not show any activity against A549 and MCF-7 cell lines.
DNA represents one of the most important cellular molecular targets of several anticancer drugs. The compounds exhibited varied amount of DNA binding activity in the range of 30 per cent to 78 per cent. Compound with (R1 = 5,7-dibromo) showed 78 per cent of DNA binding and compound (R1 = 5-Chloro) showed 60 per cent DNA binding activity.
The test compounds exhibited varied range of cytotoxicty against the three cell lines employed except compounds (R2 = 7-caboxy) and (R1 = 1-acetyl), which did not show activity against MCF-7 (breast cancer) and A549 (lung cancer) cell lines. Most of the compounds showed goodanticancer activity against HEPG2 cell lines.Further, the DNA binding studies reveal that the test compounds showed 30 per cent to 78 per cent of DNA binding activity. Compounds (R2 = 5,7-dibromo) and (R2 = 5-chloro) showed more DNA binding activity among all the compounds.