New Di(heteroaryl)ethenes as Apoptotic Anti‐proliferative Agents Towards Breast Cancer: Design, One‐Pot Synthesis and In Vitro Evaluation

Abstract

A new series of di(heteroaryl)ethenes was designed and synthesized by combining 5‐(dichlorophenyl)‐furan‐2‐yl and N‐substituted pyridinum moieties. All the synthesized compounds were screened for their anticancer activity against the MCF‐7 human breast cancer cell line. Most of the tested compounds showed moderate to potent cell growth inhibition; in particular, four of these exhibited promising cytotoxicity against this cell line, with IC50 values in the range of 0.30–0.005 μM. In addition, the potential mechanism of cell growth inhibition and apoptotic induction by these compounds was investigated by using flow cytometry and confocal microscopy. Based on these results, we identified a new and alternative class of anticancer agents that have the potential to be developed as leads.

Heteroaryl-Ethylenes as New Lead Compounds in the Fight against High Priority Bacterial Strains

“…We used this model for the external prediction of more than seventy-five structures from our in-house database of heteroaryl-ethylenes (yellow circles in Figure 1 inset indicate the predicted compounds) [ 18 , 19 , 20 ]; we selected six promising candidates (PB1–6) [ 18 , 20 ] and designed two new molecules (PB7–8). This statistical and molecular modelling approach allowed us not only to highlight a promising scaffold (positioned in the lower left-hand corner of the 2D scores plot in Figure 1 but also to define key molecular properties, as molecular interaction fields (MIFs)-based descriptors that correlate with activity for drug candidates.…”

“…Proceeding on this track, we aimed to define new antimicrobial candidates starting from an in-house database of heteroaryl-ethylenes which were previously tested in vitro for their antitumor activity on different human cancer cell lines [ 18 , 19 , 20 ]. The stilbene structure can be considered a privileged scaffold as it occurs frequently both in biologically active natural compounds (i.e., resveratrol) and in synthetic derivatives [ 21 , 22 , 23 , 24 , 25 ], for applications ranging from the visualization of biomolecules in living systems and real-time tracking of cellular events to fluorescent dye guidance during surgeries.…”

Heteroaryl-Ethylenes as New Lead Compounds in the Fight against High Priority Bacterial Strains

“…For PB1 to BP6, the results were in line with data previously reported for human breast cancer cell line. [40,41,42] All molecules proved to be much more active than 5-Fluorouracil against CaCo-2 cells. Under the conditions tested, the less active molecule inhibits the growth and replication of cancer cells at a concentration corresponding to 1/5 of that required for 5 Fluorouracil.…”

“…PB1-6, 2-ethyl-5,6,7,8-tetrahydroisoquinolin-2-ium iodide and 5'-(dibuthylamino) [2,2'-bithiophene]-5-carbaldehyde were prepared according to literature procedures. [18][19][20]44,45] All reactions were carried out under nitrogen atmosphere unless otherwise stated. Thinlayer chromatography (TLC) was performed on Merck silica gel plates with F-254 indicator.…”

“…[17][18][19] The stilbene structure can be considered a privileged scaffold as it occurs frequently both in biologically active natural compounds (i.e. Resveratrol) and in synthetic derivatives [20][21][22][23][24] for applications ranging from the visualization of biomolecules in living systems and real-time tracking of cellular events, to fluorescent dye guidance during surgeries. These systems offer several advantages including: easy, rapid, efficient and inexpensive synthetic procedures; good ADME properties and high photo-stability.…”