Synthesis of Novel 2-(Het)arylpyrrolidine Derivatives and Evaluation of Their Anticancer and Anti-Biofilm Activity

Abstract

A library of novel 2-(het)arylpyrrolidine-1-carboxamides were obtained via a modular approach based on the intramolecular cyclization/Mannich-type reaction of N-(4,4-diethoxybutyl)ureas. Their anti-cancer activities both in vitro and in vivo were tested. The in vitro activity of some compounds towards M-Hela tumor cell lines was twice that of the reference drug tamoxifen, whereas cytotoxicity towards normal Chang liver cell did not exceed the tamoxifen toxicity. In vivo studies showed that the number of surviving animals on day 60 of observation was up to 83% and increased life span (ILS) was up to 447%. Additionally, some pyrrolidine-1-carboxamides possessing a benzofuroxan moiety obtained were found to effectively suppress bacterial biofilm growth. Thus, these compounds are promising candidates for further development both as anti-cancer and anti-bacterial agents.

Synthesis and Antioxidant Capacity of Some Derivatives of Sesamol at the C‐6 Position

“…The results obtained on the substitution in the indicated position are also consistent with the literature on other previously obtained mono‐C‐6‐derivatives of sesamol, such as kakuol and its analogs, [25] Mannich and Betti bases [26–32] diarylbutanes, [33] (het)arylpyrrolidines, [34] allylsesamol [35] …”

Novel Hybrid Compounds Containing Benzofuroxan and Aminothiazole Scaffolds: Synthesis and Evaluation of Their Anticancer Activity

“…Cytotoxic effects of the test compounds on human cancer and normal cells were estimated by means of the multifunctional Cytell Cell Imaging system (GE Health Care Life Science, Danderyd, Sweden) using the Cell Viability Bio App which precisely counts the number of cells and evaluates their viability from fluorescence intensity data [ 48 ]. DAPI and propidium iodide were purchased from Sigma.…”

2‐(Het)aryl‐N‐phosphorylpyrrolidines via Cyclization of Phosphorus Acid Amides: A Regioselective Approach

“…Based on this data and our previous efforts on 2‐substituted pyrrolidines synthesis, we anticipated that a similar reaction of N ‐(4,4‐diethoxybutyl)amides of P(V) acids with electron‐rich (het)aryl nucleophiles would afford N ‐phosphorylated 2‐(het)aryl‐substituted pyrrolidine derivatives via intermediate 2‐ethoxypyrrolidine formation. Notably, the presence of phosphorylation‐sensitive groups in a nucleophile should not interfere with the reaction, thus allowing regioselective synthesis of hitherto unknown N ‐phosphorylpyrrolidines possessing hydroxyl(het)aryl moiety (Scheme , B).…”