99009-93-5Relevant academic research and scientific papers
Dual inhibitors of epidermal growth factor receptor and topoisomerase IIα derived from a quinoline scaffold
Chauhan, Monika,Joshi, Gaurav,Kler, Harveen,Kashyap, Archana,Amrutkar, Suyog M.,Sharma, Praveen,Bhilare, Kiran D.,Chand Banerjee, Uttam,Singh, Sandeep,Kumar, Raj
, p. 77717 - 77734 (2018/06/22)
Based on the quinazoline bearing EGFR inhibitors, a series of thirty four compounds having a quinoline scaffold were synthesised and evaluated in vitro for EGFR kinase inhibitory activity. A structure-activity relationship study revealed that 2,4-bis(arylamino) substituted quinolines possessed better anti-EGFR kinase activity. Compounds 3f and 3m emerged as potent EGFR kinase inhibitors (200 and 210 nM, respectively) and showed excellent anticancer activity at the micromolar level against a panel of cancer cell lines comparable to erlotinib. Furthermore, representative compounds inhibited the human topoisomerase IIα selectively and catalytically, did not intercalate with DNA, increased intracellular ROS concentration (except 3m) and altered the mitochondrial membrane potential of the cancer cells. Cell cycle analysis and annexin-V staining in a lung cancer cell line showed that the compounds delayed cell cycle progression by inducing cell cycle arrest and subsequent apoptosis at the G1 phase. The facts were further corroborated through molecular modeling studies.
Synthesis and structure - Activity-relationships of 1H-imidazo[4,5-c] quinolines that induce interferon production
Gerster, John F.,Lindstrom, Kyle J.,Miller, Richard L.,Tomai, Mark A.,Birmachu, Woubalem,Bomersine, Shannon N.,Gibson, Shiela J.,Imbertson, Linda M.,Jacobson, Joel R.,Knafla, Roy T.,Maye, Peter V.,Nikolaides, Nickolas,Oneyemi, Folakemi Y.,Parkhurst, Gwen J.,Pecore, Sharon E.,Reiter, Michael J.,Scribner, Lisa S.,Testerman, Tracy L.,Thompson, Natalie J.,Wagner, Tammy L.,Weeks, Charles E.,Andre, Jean-Denis,Lagain, Daniel,Bastard, Yvon,Lupu, Michel
, p. 3481 - 3491 (2007/10/03)
1H-Imidazo-[4,5-c]quinolines were prepared while investigating novel nucleoside analogues as potential antiviral agents. While these compounds showed no direct antiviral activity when tested in a number of cell culture systems, some demonstrated potent inhibition of virus lesion development in an intravaginal guinea pig herpes simplex virus-2 assay. We have determined that the in vivo antiviral activity can be attributed to the ability of these molecules to induce the production of cytokines, especially interferon (IFN), in this model. Subsequently, we found that the compounds also induce in vitro production of IFN in human peripheral blood mononuclear cells (hPBMCs). The in vitro results reported herein and the in vivo results reported previously led to the discovery of imiquimod, 26, which was developed as a topical agent and has been approved for the treatment of genital warts, actinic keratosis, and superficial basal cell carcinoma.
