In order to extend knowledge about pharmacophoric features responsible for ABCB1 inhibitory properties of imidazolidin-2,4-dione derivatives, 1'-[4-(4-(o-methoxyphenyl)-piperazin-1-yl)butyl]-3'-methyl-spiro(fluoren-9,5'-imidazolidine)-2',4'-dione (3) and its salt (4) with rhodanine-3-acetic acid (RA) were prepared and investigated by X-ray diffraction method, as well as their efflux modulating effects in cancer cells (mouse T-lymphoma), cytotoxic and antiproliferative activities were evaluated in vitro.
Compounds <b>1</b>-<b>3</b> were evaluated for their P-glycoprotein (P-gp/ABCB1) modulation ability, using a mouse T-lymphoma <i>MDR1</i>-transfected cell model by the rhodamine-123 accumulation assay, and displayed potent multidrug resistance (MDR)-reversing activity.
For this, we determined the ABCB1 inhibiting properties of our compounds in a mouse T-lymphoma cell line model and then evaluated the drug-enhancing properties of selected compounds in a co-application with clofazimine in our Mtb strain.
Compounds 1-14 were evaluated for their MDR-reversing activity on human ABCB1 gene transfected mouse lymphoma cells (L5178Y-MDR) through a combination of functional and chemosensitivity assays.
A series of novel imidazo[4,5-b]pyridine derivatives were synthesized and their biological activities were evaluated in vitro using parental (PAR) and multidrug resistant (MDR; ABCB1-overexpressing) mouse T-lymphoma cells.
In this study, novel metal [Zn(II), Cu(II), Mg(II), Ni(II), Pd(II), and Ag(I)] complexes of 2-trifluoroacetonylbenzoxazole previously synthesized and characterized by our group were tested for their MDR-reversing activity in comparison with the free ligands in L5178Y mouse T-lymphoma (MDR) cells transfected with human ATP-binding cassette sub-family B member 1 (ABCB1; P-glycoprotein) gene.
Compounds 1-25 were evaluated for their effects on the reversion of multidrug resistance (MDR) in cancer cells mediated by P-glycoprotein (P-gp/ABCB1), through combination of functional and chemosensitivity assays, using a human ABCB1-transfected mouse T-lymphoma cell model.
Steroid derivatives were studied for their growth-inhibitory effect, cytotoxicity, reversal of multidrug resistance, apoptosis induction, and interaction with doxorubicin on multidrug resistant human ATP-binding cassette, sub-family B, member 1 (ABCB1) gene-transfected mouse T-lymphoma cell line, and human PC-3 and LNCaP prostate cancer cell lines in vitro.
P-glycoprotein is a product of the multidrug resistance (MDR1) gene, which is a major cause of the refractoriness of malignant lymphomas to conventional chemotherapeutic regimens containing anthracycline. l-asparaginase-containing regimens such as SMILE (steroid, methotrexate, ifosfamide, l-asparaginase, and etoposide) are effective for ENKL.
Drug accumulation was measured in a human ABCB1 gene-transfected mouse lymphoma cell line and in a human lung cancer cell line by flow cytometry; furthermore, their anticancer effects were determined in mice in vivo.
Fourteen hydantoin derivatives were synthesized and studied for their capacity to increase accumulation of ethidium bromide (EB) by mouse lymphoma cancer cells that were transfected with the human ABCB1 gene and overexpress the human ABCB1 pump.
The objectives of this study were (1) to develop a population pharmacokinetic model of high-dose methotrexate (HD-MTX) in children with acute lymphoblastic leukaemia (ALL) and malignant lymphoma (ML) in order to investigate the influence of common polymorphisms in SLC19A1, MTHFR and ABCB1 on plasma levels of MTX and (2) to estimate MTX exposure in individual patients to study the association of genetic variability in the folate metabolic pathway with MTX toxicity.
Since cytochrome P450 3A subfamily (CYP3A) enzymes are involved in the inactivation of chemotherapy drugs, we hypothesized that CYP3A and P-glycoprotein (MDR1) expression in these lymphomas could result in a poor clinical response.
The ability of phenothiazine derivatives to inhibit the transport activity of P-glycoprotein in resistant mouse lymphoma and MDR/COLO 320 cells was studied.
The aim of our study was to establish a lymphoma, cellular system where a de novo acquisition of multidrug resistance is specifically related to overexpression of a transgenic, human MDR1.
The ability of phenothiazine derivatives to inhibit the transport activity of P-glycoprotein in resistant mouse lymphoma and MDR/COLO 320 cells was studied.
Apoptosis induction and the interaction between epirubicin and the silicon-substituted compounds were studied in human MDR-1 gene-transfected mouse lymphoma and its parent cell line, Colo320/MDR-LRP and sensitive subline Colo205, by means of rhodamine 123 accumulation.
Neither codeinone nor morphine inhibited P-glycoprotein-mediated rhodamine-123 efflux in multidrug resistant mouse T lymphoma L5178 transfected with human MDR 1 gene.
When coupled with an anti-CD19 targeted antibody, this formulation was also effective at delivering an MDR1 asODN to a multidrug-resistant human B-lymphoma cell line in vitro, decreasing the activity of P-glycoprotein.