Preparation of a Series of Novel Bichalcones Linked with a 1,4-Dimethylenepiperazine Moiety and Examination of Their Cytotoxicity

Abstract

The chalcone basic skeleton is a unique template which is associated with widespread biological activities. In the present study, a series of novel bichalcones linked with a 1,4-dimethylenepiperazine moiety was prepared through Mannich reaction and Clasien-Schmidt condensation. The synthetic analogs 2-16 were subjected into the cytotoxicity examinations using a panel of 25 human tumor cell lines. Among the tested compounds, 3 and 4 which possessed the 3-pyridyl and phenyl groups as the substructure, respectively, displayed significant cytotoxicity against all the tumor cell lines. The results suggested that these bichalcones were potential to be the anticancer lead drugs.

Suppression of phospho‐p85α–GTP‐Rac1 lipid raft interaction by bichalcone analog attenuates cancer cell invasion

“…Actinomycin D (ActD), Brij 98, Coomassie blue R250, crystal violet, glutathione agarose beads, propidium iodide (PI), gelatin type B, paraformaldehyde, 1,4‐diamino‐2,3‐dicyano‐1,4‐bis(methylthio) butadiene (U0126), 2‐(4‐morpho‐linyl)‐8‐phenyl‐4H‐1‐benzopyran‐4‐one (LY294002), 4‐(4‐fluorophenyl)‐2‐(4‐hydroxyphenyl)‐5‐(4‐pyridyl) 1H‐imidazole (SB202190), 1,9‐pyrazoloanthrone (SP600125), 8‐[4‐(1‐aminocyclobutyl) phenyl]‐9‐phenyl‐1,2,4‐triazolo[3,4‐f] naphthyridin‐3(2H)‐one dihydrochloride (MK‐2206), pyrrolidine dithiocarbamate (PDTC), Tris‐HCl, Triton X‐100, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), and N‐ p ‐tosyl‐ L ‐phenyl‐alanine chloromethyl ketone (TPCK) were obtained from Sigma–Aldrich (St. Louis, MO). TSWU‐CD4 was prepared as previously described . DMSO and potassium phosphate were purchased from Merck (Darmstadt, Germany).…”

“…Our recent studies of new anti‐cancer synthetic agents have demonstrated that the most effective bichalcone analog (2E,2′E)‐1,1′‐(5,5′‐(piperazine‐1,4‐diylbis(methylene))bis(4‐hydroxy‐3‐methoxy‐5,1‐phenylene))bis(3‐phenylprop‐2‐en‐1‐one, or TSWU‐CD4), which contains a phenyl group on the B‐ring of the chalcone basic skeleton, exhibited the strongest cytotoxicity to all of the studied human cancer cells among all of the TSWU‐CD analogs . The molecular mechanism by which TSWU‐CD4 regulated the inhibition of cancer cell invasion remains to be further addressed.…”

Synthesis and in Vitro Biological Activity Study of Novel Phenol Mannich Base Analogs Containing Spiroheterocycle as Core Compound

“…In addition to that, the lipophilic properties of the drug molecules could be enhanced, if the suitable amine containing reagent is utilized in the Mannich base reaction [2]. The phenolic Mannich bases are classified as the C-Mannich bases which tends to forms C-C bonds and are considered as a very important class of the compounds due to their biological activities such as antibacterial activities [3], [4], antimycobacterial activities [5], [6], anticancer and cytotoxic activities [7]- [9], anti-inflammatory activities [10], [11], antihepatitis-B activities [12,13], antiviral activities [14]- [16], and antifungal activities [17], [18], analgesic activities [19], anticonvulsant activities [20], [21], enzyme inhibition activities [22], antioxidant properties [23], [24], blood pressure regulation [25], [26], and platelet aggregation inhibition activities [27].…”