Quinazolinone linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates: Design, synthesis and biological evaluation as potential anticancer agents.
作者： Ahmed Kamal , E. Vijaya Bharathi , M. Janaki Ramaiah , D. Dastagiri , J. Surendranadha Reddy
DOI: 10.1016/J.BMC.2009.12.015
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摘要: Abstract A series of novel quinazolinone linked pyrrolobenzodiazepine (PBD) conjugates were synthesized. These compounds 4a – f and 5a prepared in good yields by linking C-8 DC-81 with moiety through different alkane spacers. tested for anticancer activity against 11 human cancer cell lines found to be very potent agents GI 50 values the range 5c was a panel 60 cells. This compound showed individual 4b induced release cytochrome c , activation caspase-3, cleavage PARP subsequent death. Further, these when treated A375 cells characteristic features apoptosis like enhancement levels p53, p21 p27 inhibition cyclin dependent kinase-2 (CDK2) suppression NF-κB. Moreover, two control proliferation regulating anti-apoptotic genes (B-cell lymphoma 2) Bcl-2. Therefore, data generated suggests that PBD activate p53 inhibit NF-κB thereby could promising better therapeutic potential tumours.
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