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

Author(s):Show less -

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]}

Affiliation

^[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

• Document type: Journal article
• Source: COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS; v. 626, OCT 5 2021.
• Web of Science Citations: 0

Abstract

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 Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/27078-0 - Development of acoustic levitation systems
• Grantee: Marco Aurélio Brizzotti Andrade
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/16092-5 - Investigating colloidal systems by scattering methods
• Grantee: Cristiano Luis Pinto de Oliveira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/50983-3 - INCT 2014: complex fluids
• Grantee: Antonio Martins Figueiredo Neto
• Support Opportunities: Research Projects - Thematic Grants