1214739-65-7Relevant academic research and scientific papers
Quinazolino linked 4β-amidopodophyllotoxin conjugates regulate angiogenic pathway and control breast cancer cell proliferation
Kamal, Ahmed,Tamboli, Jaki R.,Ramaiah, M. Janaki,Adil,Pushpavalli,Ganesh, Raksha,Sarma, Pranjal,Bhadra, Utpal,Pal-Bhadra, Manika
, p. 6414 - 6426 (2013/10/22)
A series of new conjugates of quinazolino linked 4β- amidopodophyllotoxins 10aa-af and 10ba-bf were synthesized and evaluated for their anticancer activity against human pancreatic carcinoma (Panc-1) as well as breast cancer cell lines such as MCF-7 and MDA-MB-231 by employing MTT assay. Among these conjugates, some of them like 10bc, 10bd, 10be and 10bf exhibited high potency of cytotoxicity. Flow cytometric analysis showed that these conjugates arrested the cell cycle in the G2/M phase and caused the increase in expression of p53 and cyclin B1 protein with concomitant decrease in Cdk1 thereby suggesting the inhibitory action of these conjugates on mitosis. Interestingly, we observed a decrease in expression of proteins that control the tumor micro environment such as VEGF-A, STAT-3, ERK1/2, ERK-p, AKT-1 ser 473 phosphorylation in compounds treated breast cancer cells. Further, these effective conjugates have exhibited inhibitory action on integrin (αVβIII). Furthermore, the MCF-7 cells that were arrested and lost the proliferative capacity undergo mitochondrial mediated apoptosis by activation of caspases-9. Thus these conjugates have the potential to control breast cancer cell growth by effecting tumor angiogenesis and invasion.
Quinazolinone linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates: Design, synthesis and biological evaluation as potential anticancer agents
Kamal, Ahmed,Vijaya Bharathi,Janaki Ramaiah,Dastagiri,Surendranadha Reddy,Viswanath,Sultana, Farheen,Pushpavalli,Pal-Bhadra, Manika,Srivastava, Hemant Kumar,Narahari Sastry,Juvekar, Aarti,Sen, Subrata,Zingde, Surekha
experimental part, p. 526 - 542 (2010/04/26)
A series of novel quinazolinone linked pyrrolobenzodiazepine (PBD) conjugates were synthesized. These compounds 4a-f and 5a-f were prepared in good yields by linking C-8 of DC-81 with quinazolinone moiety through different alkane spacers. These conjugates were tested for anticancer activity against 11 human cancer cell lines and found to be very potent anticancer agents with GI50 values in the range of 50 values of 0.1 μM. The thermal denaturation studies exhibited effective DNA binding ability compared to DC-81 and these results are further supported by molecular modeling studies. The detailed biological aspects of these conjugates on A375 cell line were studied. It was observed that compounds 4b and 5c induced the release of cytochrome c, activation of caspase-3, cleavage of PARP and subsequent cell death. Further, these compounds when treated with A375 cells showed the characteristic features of apoptosis like enhancement in the levels of p53, p21 and p27 inhibition of cyclin dependent kinase-2 (CDK2) and suppression of NF-κB. Moreover, these two compounds 4b and 5c control the cell proliferation by regulating anti-apoptotic genes like (B-cell lymphoma 2) Bcl-2. Therefore, the data generated suggests that these PBD conjugates activate p53 and inhibit NF-κB and thereby these compounds could be promising anticancer agents with better therapeutic potential for the suppression of tumours.
