Nanoparticles of 4,7‐dichloro‐2‐quinolinemethylacrylate‐based copolymers and their potential cytotoxic activity on human breast carcinoma cells

Abstract

In this article, an improved synthesis strategy of the potent anticancer compound 4,7-dichloro-2-quinolinemethanol (QM) and its acrylate ester 4,7-dichloro-2-quinolinemethylacrylate (AQM) are described. AQM is copolymerized using free-radical polymerization with N-vinyl-2-pyrrolidone (VP) and the copolymers obtained from different molar ratios of monomers are subjected to nanoprecipitation to produce suspensions of nanoparticles (NPs) in phosphate buffered saline (PBS). The smallest and stable NPs are prepared with the AQM-VP copolymers 45:55 and 40:60 (118.9 and 128.7 nm in diameter, respectively) at 1 mg mL −1 , and along with AQM and QM, are evaluated for their cytotoxic activity on MDA-MB-453 breast carcinoma cells using MTT bioassay. AQM and QM are highly cytotoxic (IC 50 : 19 and 41 μM, respectively); however, the NPs are not cytotoxic in the range of the assayed concentrations. These results contribute to the search for new polymeric NPs with potential application as QM delivery systems for the treatment of cancer or other diseases treatable with QM.There are several cellular internalization mechanisms that are influenced by the physicochemical properties of the NPs. These are phagocytosis, macropinocytosis, clathrin-mediated endocytosis, and caveolae-mediated endocytosis. With the exception of the last Additional Supporting Information may be found in the online version of this article.

Nanocarrier of α-Tocopheryl Succinate Based on a Copolymer Derivative of (4,7-dichloroquinolin-2-yl)methanol and Its Cytotoxicity against a Breast Cancer Cell Line

“…The thermal stability of the copolymers (~5 mg) was analyzed by thermogravimetric analysis using a TGA Q500 (TA Instruments, New Castle, DE, USA) under a nitrogen atmosphere (50 mL min −1 ) at 10 • C min −1 heating rate from 25 to 600 • C. Both the onset and weight loss values were calculated using TA Instruments Universal Analysis Software (v. 4.5A). [14,32] To obtain unloaded NPs, copolymer solutions were prepared in THF:DMF (7:3) with a 5 mg mL −1 concentration. A total of 2.5 mL of each solution was added dropwise to 10 mL of PBS (phosphate buffered solution, pH 7.4), i.e., in 1:4 (v/v) proportion, under constant magnetic stirring, and then was dialyzed against PBS for 24 h (with a membrane of 3.5 kDa molecular weight cutoff) to remove the organic solvent.…”

Antibacterial Activity and Fluorescence Properties of 4,7-Dichloro-2-Quinolinemethylacrylate

“…24 This double biological activity is probably due to the similarity of certain biochemical processes of human and bacterial cells (e.g., cell division or cellular respiration) in which structurally similar biomolecules participate, which would be the therapeutic target for these quinolinic drugs. 8 It is noteworthy that Valle et al recently reported the synthesis of the new molecule AQM, which showed potent cytotoxic activity against breast carcinoma cells MDA-MB-453 (IC50: 19 μM); 25 however, its potential antibacterial activity has not been evaluated. In the present work, we investigated the antibacterial activity of AQM on six bacterial species, two pathogenic bacteria for humans (Klebsiella pneuminiae and Staphylococcus aureus), three phytopathogenic bacteria (Pcc, Ralstonia solanacearum and Pseudomonas syringae) and Bacillus sp.…”