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

Rapid and Facile Synthesis of Isomaleimides: Dehydration of Maleamic Acids using Methanesulfonyl Chloride

“…Maleamic acids 3 were prepared according to a reported procedure. 3,16 Spectroscopic data of 4a, 4b, 4d, 4f, 4h, 4l, 4o, 4p, 4s, and 4t are in agreement with the reported data. 7,8,15 Synthesis of Isomaleimides from Maleamic Acid: General Procedure Maleamic acid 3 (0.2 mmol) was taken into a 7 mL vial and EtOAc (1 mL, 0.2 M) was added.…”

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.…”

Discovery of Novel Topoisomerase II Inhibitors by Medicinal Chemistry Approaches

“…Additionally, because topo IIα is a thiol-rich enzyme and is crucial for sustained cell proliferation, Michael acceptors (e.g., an α,β-unsaturated carbonyl group) and the enone unit are suitable for incorporation into the curcumin motif with the expectation of furnishing selective affinity for topo IIα upon forming interactions with auxiliary binding sites. On the basis of these data, a spectrum of keto-type curcumin derivatives with a maleic diamide tether ( 85 , Figure ) were prepared and assessed . These derivatives manifested heightened top IIα-related cytotoxicity by approximately 93- to 280-fold compared with the controls (curcumin and melphalan), suggesting the possibility, although questionable, of developing more potent curcumin-derived compounds.…”