Synthesis and biological evaluation of 6-fluoro-3-phenyl-7-piperazinyl quinolone derivatives as potential topoisomerase I inhibitors

Design, synthesis, molecular docking and cytotoxicity evaluation of some novel 5-arylidene-3-(substituted phenyl)-2-(p-tolylamino)-4-imidazolones

“…Topoisomerase I (topo I) is a ubiquitous nuclear enzyme that is involved in solving all topological problems associated with DNA replication and transcription which acts by making a transient break in one strand of DNA followed by rejoining of the DNA strand after passing one strand through each other resulting in relaxation of the supercoiled DNA (Topcu, 2001;Ge et al, 2016;Mazza et al, 2016; Cheng-Kang Peng and Lin, 2017).…”

“…Great efforts have been conducted to develop safe and more effective topo I inhibitor with improved stability based on the structure activity relationships (SAR) and binding interactions of the reported topo I inhibitors, (Figure 1) (Hou et al, 2016;Zhang et al, 2016). In addition to camptothecin, indolocarbazoles and indenoisoquinolines, different scaffolds have been reported to have topo I inhibitory activity despite the loss of planar structure that found in the classic topo I poisons like substituted aryl pyridines, indeno-naphthyridines, substituted quinolones and substituted 2-thioxoimidazolidinones (Majumdar et al, 2015;Alonso et al, 2016;Ge et al, 2016;Park et al, 2017). Herein, we designed and synthesized 5-arylidene-3-(substituted phenyl)-2-(p-tolylamino)-3,5-dihydro-4H-imidazol-4-ones based on compounds (I) and (II) through modification of the structure of compound (I) by adding different p-substituted arylidene groups at position 5 through knoevenagel condensation reaction with different P-substituted benzaldehydeand psubstituted phenyl at position 3 instead of H in compound (I) and different from compound (II) also, the sulfur atom was replaced by p-tolylamino group through nucleophilic substitution reaction with P-toluidine; to study the impact of these modifications on the cytotoxicity and binding interactions with topo I, (Figure 2).…”

Synthesis, Molecular Docking and Biological Evaluation of Quinolone Derivatives as Novel Anticancer Agents

“…[4][5][6][7] Li and colleagues designed and synthesized a series of quinolone derivatives as potential Top I inhibitors for cancer treatment. [8][9][10] Rajulu et al designed a series of fluoroquinolones displaying good growth inhibition activities against human lung carcinoma cell (A549) and colon carcinoma (HCT-116). 11) Recently, our group discovered a novel series of Top I inhibitors with quinolone scaffold.…”