Investigation of fatty acid conjugates of 3,5-bisarylmethylene-4-piperidone derivatives as antitumor agents and human topoisomerase-IIα inhibitors

Synthesis, human topoisomerase IIα inhibitory properties and molecular modeling studies of anti-proliferative curcumin mimics

“…Reports described the topoisomerase IIa inhibitory properties of 1,3-ylidene-4-piperidones encouraged these studies. 21,22 From the results obtained (Table 4 and Fig. 2 28.97 mM, respectively).…”

“…Interest in the piperidone ring system originate from the diverse biological properties showed by 1,3-diarylidene-4piperidones as antitumor, [18][19][20][21][22][23][24] anti-mycobacterial, 25 antimalarial 26 and acetylcholinesterase inhibitor suggesting the usefulness for Alzheimer's disease treatment. 27 The promising properties of 2,4-bis(arylidene)-8-methyl-8-azabicyclo[3.2.1] octan-3-ones against MCF7 (breast) and HepG2 (liver) carcinoma cell lines also prompted the present study.…”

Curcumin-inspired cytotoxic 3,5-bis(arylmethylene)-1-(N-(ortho-substituted aryl)maleamoyl)-4-piperidones: A novel group of topoisomerase II alpha inhibitors

“…Sorafenib, a multi-target kinase inhibitor, is also known to inhibit topoisomerase IIα in-vitro [39,40] and in-vivo [41]. The results from this evaluation showed that all the assayed compounds, including reference drugs (50 µM), exhibited strong inhibitory activity towards topo IIα in vitro.…”

“…Likewise, the molar refractivity (MR mol ) values and the calculated partition coefficient (logP) of series 9 compounds were also obtained using the same commercial software [40] and utilized as a means of assessing the effect of steric properties and lipophilicity, respectively, of the compounds with respect to their bioactivity. Physicochemical parameters of the aromatic substituents [44] such as Taft E s steric constant for orthosubstituents, Hansch π (a measure of the lipophilicity of the substituents), and molar refractivity (MR sub, (a measure of the size of the substituents) were also used for statistical correlation studies.…”

Synthesis and in Vitro Bioactivity of Polyunsaturated Fatty Acid Conjugates of Combretastatin A-4

“…Studies have shown that there is a selective uptake of PUFAs into cancerous cells compared to healthy cells and that the incorporation of PUFAs into the lipid bilayer of the cancer cells disrupts their membrane structure and fluidity, which as a result seems to modify their chemosensitivity . In the context of targeted therapies, conjugation of PUFAs to conventional cytotoxic drugs has been a promising strategy, with Taxoprexin (paclitaxel/docosahexaenoic acid) reaching phase III clinical trials . Applying this same general concept to combretastatins could minimize some of the unwanted side effects and improve their therapeutic indices.…”