DNA fragmentation, cell cycle arrest, and docking study of novel bis spiro-cyclic 2-oxindole of pyrimido[4,5-b]quinoline-4,6-dione derivatives against breast carcinoma.

DNA fragmentation, cell cycle arrest, and docking study of novel bis spiro-cyclic 2-oxindole of pyrimido[4,5-b]quinoline-4,6-dione derivatives against breast carcinoma. Curr Cancer Drug Targets. 2017 Jun 30;: Authors: Mohamed MF, Abdelmoniem AM, Elwahy AHM, Abdelhamid IA Abstract An efficient one pot synthesis of bis spiro-cyclic 2-oxindole derivatives of pyrimido[4,5-b]quinoline-4,6-dione using 6-aminouracil, bis-isatin and dimedone has been developed. The cytotoxic effect against different human cell lines MCF7, HCT116 and A549 cell lines was evaluated. The derivative 6a, was found the most encouraging compound in this series and it was selected for molecular studies against MCF7. Our data indicated that compound 6a is an attractive target for breast cancer, as it inhibits proliferation, cell cycle progression and induces apoptosis of tumor cells. This inhibition is mediated by fragmentation of genomic DNA, up-regulation of [caspase-3, tumor suppressor gene p53, and pro-apoptotic gene BAX], and down-regulation of anti-apoptotic BCL2 gene. In additions it caused cell cycle arrest in S phase. This work provides an evidence of the potent effect of the new compound 6a and assists in the progress of new healing agents for cancer. PMID: 28669339 [PubMed - as supplied by publisher]
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research