Search results for "SoMe"
showing 10 items of 5114 documents
Quinoline anticancer agents active on DNA and DNA-interacting proteins: From classical to emerging therapeutic targets.
2021
Quinoline is one of the most important and versatile nitrogen heterocycles embodied in several biologically active molecules. Within the numerous quinolines developed as antiproliferative agents, this review is focused on compounds interfering with DNA structure or with proteins/enzymes involved in the regulation of double helix functional processes. In this light, a special focus is given to the quinoline compounds, acting with classical/well-known mechanisms of action (DNA intercalators or Topoisomerase inhibitors). In particular, the quinoline drugs amsacrine and camptothecin (CPT) have been studied as key lead compounds for the development of new agents with improved PK and tolerability…
Carcinogenic aspect of xenobiotic molecules belonging to the peroxisome proliferator family.
1999
It is known that a short-term exposure of rat, mice or incubation of hepatic cells with fibrate molecules leads to increase in peroxisome number and cell hyperplasia. Further, long-term incubation of cells (at least a year) show transformed characteristics with foci and nodules. To explain the hepatocarcinogenic effect of peroxisome proliferators in rodents we studied the effect of peroxisome proliferators on rat liver oncogenes expression. Earlier, we reported an increase in liver and kidney mRNA level of c-myc and N-myc. Since several metabolic genes are activated by PPAR (peroxisome proliferators activated receptor) through a PPRE (peroxisome proliferator response element), we suggest th…
Synergistic cytotoxic interactions between sodium butyrate, MG132 and camptothecin in human retinoblastoma Y79 cells.
2000
This paper studies the effects caused in human retinoblastoma Y79 cells by treatment with combinations of sodium butyrate, the inhibitor of topoisomerase I camptothecin and the inhibitor of 26S proteasome MG132. The combination of sodium butyrate and camptothecin resulted in a strong synergistic cytotoxicity, as revealed by combination indices of 0.77 and 0.52 calculated at IC(50) and IC(75). Synergistic interactions were also demonstrated for combinations of sodium butyrate and MG132, camptothecin and MG132 and for a combination of all three compounds. The cytotoxic effects observed after the combined treatments can be considered a consequence of apoptosis, as suggested by the appearance o…
Preparation of a dansylated fibrate, a new fluorescent tool to study peroxisome proliferation. Effect on hepatic-derived cell lines.
1997
The synthesis of a dansylated fibrate (DNS-X) has been performed in order to identify the cellular affinity sites of peroxisome proliferators and to establish the subcellular localization of such molecules. DNS-X has been obtained by coupling the dansy1 chloride with the amine resulting from the bezafibrate alkaline hydrolysis. The purified DNS-X has been further characterized by spectrum analysis (UV-Vis, fluorescence, [1H]/[13C]-NMR and mass). At 250 microM and incubated for 48 h with the rat hepatic derived cells (Fao cells), DNS-X stimulates 12-fold the palmitoyl-CoA oxidase, a peroxisome proliferation marker enzyme. This increase is comparable to the one obtained with well known peroxi…
Repurposing of the ALK inhibitor crizotinib for acute leukemia and multiple myeloma cells
2021
Crizotinib was a first generation of ALK tyrosine kinase inhibitor approved for the treatment of ALK-positive non-small-cell lung carcinoma (NSCLC) patients. COMPARE and cluster analyses of transcriptomic data of the NCI cell line panel indicated that genes with different cellular functions regulated the sensitivity or resistance of cancer cells to crizotinib. Transcription factor binding motif analyses in gene promoters divulged two transcription factors possibly regulating the expression of these genes, i.e., RXRA and GATA1, which are important for leukemia and erythroid development, respectively. COMPARE analyses also implied that cell lines of various cancer types displayed varying degr…
(+)-Dehydroabietylamine derivatives target triple-negative breast cancer.
2015
Breast cancer remains the leading cause of cancer-related death among women. The invasive triple-negative subtype is unresponsive to estrogen therapy, and few effective treatments are available. In search of new chemical scaffolds to target this disease, we conducted a phenotypic screen against the human breast carcinoma cell lines MDA-MB-231, MA11, and MCF-7 using terrestrial natural products. Natural products that preferentially inhibited proliferation of triple-negative MDA-MB-231 cells over estrogen receptor-positive cells were further studied; herein we focused on the abietanes. The activity of the abietane carnosol prompted us to generate a focus library from the readily available (+)…
Immunonegative Staining: Epitope Localization on Macromolecules
1996
Relevant literature relating to immunonegative staining is reviewed and integrated with current research of the author and others. The immunonegative staining procedure has been utilized for the study of epitope localization on immune complexes formed from keyhole limpet hemocyanin type 2 (KLH2) di- and multidecamers, and the 20S and 26S proteasome from Xenopus laevis. The IgG linkage pattern of molecules in small immune complexes is considered to provide the most reliable indication of epitope location. For both KLH2 and the 20S proteasome, using domain-specific monoclonal antibodies and a 32-kDa (p32) subunit-specific polyclonal antibody, respectively, it is shown that epitopes (KLH2, sub…
Design, synthesis, DNA-binding and cytotoxicity evaluation of new potential combilexines
2002
Combilexines, compounds in which a DNA intercalator is linked to a minor groove binding component, interact with the DNA in a sequence specific manner to yield in most cases compounds with anticancer activity. A series of new compounds closely related to netropsin in which the two components were linked by an amide group was synthesised as potential combilexines. As some of these compounds showed cytotoxic activity in vitro, an attempt was made to rationalise their mechanism of action. The DNA binding characteristics of the carboxamides were evaluated by thermal denaturation experiments and by ethidium bromide displacement assay. Their ability to inhibit the topoisomerase I was also determi…
Stereoselective Synthesis of the Antiprotozoal Lactone Passifloricin A and Seven Isomers Thereof
2004
The conjugated delta-lactone passifloricin A, a natural product with antiprotozoal activity, and seven isomers thereof have been synthesized in enantiopure form. It has been shown in this way that the proposed structure for the natural compound was erroneous. The correct structure is now evidenced. Key steps of the syntheses were asymmetric Brown-type aldehyde allylations and ring-closing metatheses.
BCR-ABL as a target for novel therapeutic interventions.
2002
The BCR-ABL oncogene is the result of a reciprocal translocation between the long arms of chromosome 9 and 22 t(9; 22). There is good experimental evidence demonstrating that BCR-ABL is the single causative abnormality in chronic myeloid leukaemia (CML), making it a unique model for the development of molecular targets. In addition to CML, BCR-ABL transcripts can be found in a minority of acute lymphoblastic leukaemias and very rarely in acute myeloid leukaemia (AML). Elucidating the molecular mechanisms and downstream pathways of BCR-ABL has led to the design of several novel therapeutic approaches. In this review, molecular targeting of BCR-ABL will be discussed based on the inhibition of…