Design and synthesis of anti-breast cancer agents from 4-piperazinylquinoline: A hybrid pharmacophore approach

Activation of 6-bromoquinoline by nitration: synthesis of morpholinyl and piperazinyl quinolines

“…The Noxidations of 6-bromo (13) and 6,8-dibromoquinoline (19) were carried out in the presence of AcOH/H2O2 or m-CPBA (Scheme 5). Both AcOH/H2O2 and m-CPBA reacted smoothly with (13) and afforded the N-oxide derivative (20) in good yield (60% and 87%, respectively). Several attempts to effect the same results for the N-oxidation of (19) to yield (21) failed, however, under the same or similar conditions.…”

“…To afford the 2-and 4-nitro-substituted-bromoquinoline derivatives (22) and (23), it was first attempted to convert bromoquinolines (13) and (19) into the quinoline N-oxides (20) and (21), respectively (Scheme 4). which facilitated the nitration at the pyridine ring of the quinoline moiety due to +R effect of the N-oxide form.…”

“…Although the piperazine-and morpholine-substituted quinolines have a wide range of biological importance, [13][14] the available literature lacks syntheses of these piperazine-and morpholine-based derivatives on the benzene ring of quinolines by substitution methods.…”

Synthesis of Certain 2-Substituted-1<i>H</i>-benzimidazole Derivatives as Antimicrobial and Cytotoxic Agents

“…[21][22][23] Recently, certain 2-substituted benzimidazole Schiff bases were found to display potent anti-proliferative activity against HeLa and MCF-7 cell lines. 3) From the view point of molecular design, the combination of two biologically active molecules or pharmacophores is a well-known approach for the build-up of drug-like molecules, 24,25) which allows us to find more potent agents. In light of the antimicrobial, antifungal and antiproliferative importance of benzimidazole, azo compounds and Schiff bases it was thought that it would be of interest to synthesize a single molecule containing more than one pharmacophore (hybrids or conjugates).…”

“…These merged pharmacophores, may be addressing the active site of different targets for the purpose to overcome drug resistance, as well as reducing unwanted side effects. 24) The present work comprises the combination of 2-aminobenzimidazole pharmacophore with various substituted aromatic or heterocyclic rings via azo or azomethine linker, (compounds 2a-d, 3a-c, 4, 5a, b) (Charts 1-3), to study the potential additive effect of the combined molecule towards antimicrobial and cytotoxic activities. It was interesting to synthesize hybrids between 2-aminobenzimidazole pharmacophore and certain substituted pyrazoles possessing anticancer and antimicrobial activities [26][27][28] or the common analgesic drug, floctafenine to give compounds 3a-c, respectively (Chart 2), hoping that this combination may possess a potential analgesic activity along with possible anticancer effect.…”