In vitro and in vivo multidrug resistance reversal activity by a Betti-base derivative of tylosin

Abstract

Background:The multidrug resistance (MDR) proteins are present in a majority of human tumours. Their activity is important to understand the chemotherapeutic failure. A search for MDR-reversing compounds was conducted among various Betti-base derivatives of tylosin.Methods:Here, we evaluate the in vitro and in vivo P-glycoprotein (P-gp)-modulating activity of the most promising compound N-tylosil-1-α-amino-(3-bromophenyl)-methyl-2-naphthol (TBN) using human MDR1 gene-transfected and parental L5178 mouse lymphoma cell lines.Results:In vitro experiments showed that TBN dramatically increased the P-gp-mediated cellular uptake of the fluorescent substrate rhodamine 123. Similarly, TBN was found to act as a very potent enhancer of the cytotoxicity of doxorubicin on the resistant cell line. We also provide in vivo evidence using DBA/2 mice in support for an increased tumoural accumulation of doxorubicin, without affecting its tissue distribution, resulting in an enhanced antitumoural effect.Conclusion:Our results suggest that TBN is a potent modulator of the P-gp membrane pump and that the compound could be of clinical relevance to improve the efficacy of chemotherapy in MDR cancers.

Guizhi Fuling Wan, a Traditional Chinese Herbal Formula, Sensitizes Cisplatin‐Resistant Human Ovarian Cancer Cells through Inactivation of the PI3K/AKT/mTOR Pathway

“…The ability of GFW to potentiate the antitumour activity of cisplatin/paclitaxel was evaluated using the SKOV3/DDP xenografts as described previously [ 29 ]. Briefly, female BALB/c nude mice, aged between 3 and 4 weeks and weighing 20~22 g, were housed in standard microisolator conditions free of pathogens and used in accordance with the Animal Care and Use protocol approved by Nanyang Institute of Technology.…”

Synthesis and application of novel 1,2,3‐triazolylferrocene‐containing ionic liquid supported on Fe3O4 nanocatalyst in the synthesis of new pyran‐substituted Betti bases

“…[17][18][19][20] One of the important multicomponent reactions is the Betti reaction which was introduced by Mario Betti. [21,22] After the initial report of the synthesis of Betti bases, the study of these compounds has become an important area, [23][24][25][26] because of their significant biological, [27,28] synthetic [29][30][31][32] and catalytic [33] applications.…”

γ-aminobutyric acid and collagen peptides as recyclable bifunctional biocatalysts for the solvent-free one-pot synthesis of 2-aminobenzothiazolomethyl-2-naphthols

“…Nowadays, the name has grown to refer to any condensation reactions between aldehydes, primary aromatic amines and phenols which produce Betti base (19). The Betti reaction serves versatile synthetic building blocks with a broad range of application such as essential intermediates for many multistep organic syntheses and preparing a lot of nitrogen-containing pharmacores (20,21).…”