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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Novel cytotoxic amphiphilic nitro-compounds derived from a synthetic route for paraconic acids

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Ribeiro, Talita A. [1, 2] ; Machado-Ferreira, Erik [1] ; Guimaraes, Lohaine F. [1] ; Cavaleiro, Jessica [1, 2] ; Britto, Alan Messala A. [1] ; Redua, Nataly [3] ; Pereira de Souza, Lucas Miguel [4] ; Pimentel, Andre S. [4] ; Picciani, Paulo H. S. [2, 5] ; Oliveira, Osvaldo N. Jr Jr ; Barreto, Cleber Bonfim [3] ; Soares, Carlos Augusto G. [1, 2]
Total Authors: 12
[1] Univ Fed Rio de Janeiro, Inst Biol, UFRJ, Dept Genet, Rio De Janeiro - Brazil
[2] Univ Fed Rio de Janeiro, Biofunct Nanodevices Dev Grp, UFRJ, Rio De Janeiro - Brazil
[3] IFRJ, Inst Fed Educ Ciencia & Tecnol Rio de Janeiro, Niteroi, RJ - Brazil
[4] Pontificia Univ Catolica Rio de Janeiro, Dept Quim, BR-22453900 Rio De Janeiro, RJ - Brazil
[5] Univ Fed Rio de Janeiro, Inst Macromol Eloisa Mano, UFRJ, Rio De Janeiro - Brazil
Total Affiliations: 5
Document type: Journal article
Web of Science Citations: 0

A series of precursors for bioactive paraconic acids (PA) were synthesized and their cytotoxicity assessed on human cells in vitro. Two amphiphilic nitro-containing precursors, Nitro-C15-EED and the butanolide Nitro-C12GBL, were cytotoxic at the micromolar scale, with higher activity on tumor HeLa cells than on HEK-293T of non tumor origin. The structure of these molecules is simple but different from reported bioactive nitro compounds. Nitro-C12-GBL was generally more cytotoxic, but after short-term (2 h) exposure both compounds reached maximum cytotoxicity. At 72 h post-treatments of HeLa cells the final dose-response for Nitro-C12-GBL (LC50 = 21.9 mu mol L-1) was close to that for Nitro-C15-EED (LC50 = 25.3 mu mol L-1), corresponding to LC(50)s -3-3.6 times lower than those on HEK-293T. Short-term treatments with 50 mu mol L-1 of these compounds promoted comparable outcomes, reducing tumor cells viability up to 27-36% of the controls and preserving-70% of HEK293T viability at 72 h post-treatments. Reduced cytotoxicity was observed in cultures continuously exposed to the compounds for longer periods (24-72 h), especially on tumor cells, underlining short-term treatments as alternatives to antiproliferative strategies. Due to their amphiphilic nature, these compounds show spontaneous surface activity and adsorption onto Langmuir monolayers of dipalmitoyl phosphatidyl choline (DPPC), especially Nitro-C12-GBL. The effects on DPPC monolayers are indicative of a possible physiological action that depends on the interaction with the cell membranes. Coarse-grained molecular dynamics indicate that individualized molecules of Nitro-C15-EED and the less toxic PA precursors are susceptible to trapping into phospholipid films. In contrast, Nitro-C12-GBL consistently forms large aggregates with outward polar domains, which could favor interaction with phospholipid polar heads of biological membranes. (AU)

FAPESP's process: 18/22214-6 - Towards a convergence of technologies: from sensing and biosensing to information visualization and machine learning for data analysis in clinical diagnosis
Grantee:Osvaldo Novais de Oliveira Junior
Support type: Research Projects - Thematic Grants
FAPESP's process: 17/27078-0 - Development of acoustic levitation systems
Grantee:Marco Aurélio Brizzotti Andrade
Support type: Regular Research Grants
FAPESP's process: 18/16092-5 - Investigating colloidal systems by scattering methods
Grantee:Cristiano Luis Pinto de Oliveira
Support type: Regular Research Grants
FAPESP's process: 14/50983-3 - INCT 2014: complex fluids
Grantee:Antonio Martins Figueiredo Neto
Support type: Research Projects - Thematic Grants