296234-68-9Relevant articles and documents
Antiproliferative efficacy of n-(3-chloro-4-fluorophenyl)-6, 7-dimethoxyquinazolin-4-amine, dw-8, in colon cancer cells is mediated by intrinsic apoptosis
Abou-Dahech, Mariam Sami,Ashby, Charles R.,Balaji, Swapnaa,Karthikeyan, Chandrabose,Kumari, Shikha,Malla, Saloni,Moorthy, N. S. Hari Narayana,Neupane, Rabin,Tiwari, Amit K.,Trivedi, Piyush,Waiker, Digambar Kumar
, (2021/08/05)
A novel series of 4-anilinoquinazoline analogues, DW (1–10), were evaluated for anticancer efficacy in human breast cancer (BT-20) and human colorectal cancer (CRC) cell lines (HCT116, HT29, and SW620). The compound, DW-8, had the highest anticancer efficacy and selectivity in the colorectal cancer cell lines, HCT116, HT29, and SW620, with IC50 values of 8.50 ± 2.53 μM, 5.80 ± 0.92 μM, and 6.15 ± 0.37 μM, respectively, compared to the non-cancerous colon cell line, CRL1459, with an IC50 of 14.05 ± 0.37 μM. The selectivity index of DW-8 was >2-fold in colon cancer cells incubated with vehicle. We further determined the mechanisms of cell death induced by DW-8 in SW620 CRC cancer cells. DW-8 (10 and 30 μM) induced apoptosis by (1) producing cell cycle arrest at the G2 phase; (2) activating the intrinsic apoptotic pathway, as indicated by the activation of caspase-9 and the executioner caspases-3 and 7; (3) nuclear fragmentation and (4) increasing the levels of reactive oxygen species (ROS). Overall, our results suggest that DW-8 may represent a suitable lead for developing novel compounds to treat CRC.
