Study of the in vitro antineoplastic structure-activity relationship of cyclic analogues of terpenyl-nitronase LQB-278

Autor: Thimóteo, Rachell Ramalho Correia
Přispěvatelé: Sabino, Kátia Costa de Carvalho, Araújo, Maria da Graça Justo, Mencalha, André Luiz, Dias, Ayres Guimarães, Amorim, Lidia Maria da Fonte de
Jazyk: portugalština
Rok vydání: 2017
Předmět:
Zdroj: Biblioteca Digital de Teses e Dissertações da UERJ
Universidade do Estado do Rio de Janeiro (UERJ)
instacron:UERJ
Popis: Submitted by Boris INFORMAT (boris@uerj.br) on 2021-04-26T01:14:51Z No. of bitstreams: 1 Rachell Ramalho Correia Thimoteo Dissertacao completa.pdf: 1540652 bytes, checksum: b204f88c48325b474d195979cecbf380 (MD5) Made available in DSpace on 2021-04-26T01:14:51Z (GMT). No. of bitstreams: 1 Rachell Ramalho Correia Thimoteo Dissertacao completa.pdf: 1540652 bytes, checksum: b204f88c48325b474d195979cecbf380 (MD5) Previous issue date: 2017-02-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico Cancer currently represents a serious public health problem, and several studies are searchinh develop new molecules that have double pharmacological properties, ensuring therapeutics efficacy and lower collateral effects. The study of the structure-activity relationship of different molecules has revealed important prototypes with antitumor action. LQB-278, for example, was synthesized from the insertion of the geranyl terpene fragment into the aromatic ring of N-Phenyl-t-butylnitrone, and showed an important in vitro antileukemic action. This work studied the interference in the structural modifications of terpenyl nitrona LQB-278 concerning antineoplastic action in vitro, also evaluating the cell cycle, cell death by apoptosis and expression of p21. Cytotoxicity was measured by MTT assay with leukemic cell lines (Jurkat and K562) and solid tumors (PC3, A549 and MCF-7); In addition to non-tumor cells (NIH-3T3 fibroblasts and human peripheral blood mononuclear cells). The cells were cultured and treated or not with the test substances for 72h. Cell proliferation was assessed by the Tripan blue dye exclusion assay, and the cell cycle, apoptosis and p21 expression were performed by flow cytometry in Jurkat cells. The Jurkat lymphocytic leukemia was the most sensitive tumor cell line to the molecules under study, showing IC50 of 2.6 ± 0,6 μM, 1.4 ± 0,4 μM and 2.8 ± 0,3 μM for LQB-292, LQB-287 and LQB-461, respectively. Such molecules showed low cytotoxic action on non-tumor cells. These LQBs reduced (p
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