Zidovudine Glycosylation by Filamentous Fungi Leads to a Better Redox Stability and Improved Cytotoxicity in B16F10 Murine Melanoma Cells.

Background: The strategic development of therapeutic agents, capable of being targeted at their active sites, has been a major goal in treatment of cancer. The delivery of drugs for tumors has as its main challenge the development of safe and effective drugs, since the goal of chemotherapy is to eliminate the tumor completely without affecting healthy cells. The aim of present study was to investigate the antioxidant, anticancer activities of zidovudine and its α-O-glycosylated derivative obtained by biosynthesis of a filamentous fungi, Cunninghamela echinulata.

Small-molecule MDM2 inhibitor LQFM030-induced apoptosis in p53-null K562 chronic myeloid leukemia cells.

Our group designed and synthesized the N-phenyl-piperazine LQFM030 [1-(4-((1-(4-chlorophenyl)-1H-pyrazol-4-yl)methyl) piperazin-1-yl) ethanone], a small molecule derived from molecular simplification of the Nutlin-1, an inhibitor of the human homologue of murine double minute 2 (MDM2) protein that is expressed in several types of cancer. To better investigate the effects of LQFM030 regarding the p53 mutation status, this study investigated the antiproliferative activity of LQFM030 against the p53-null K562 leukemia cells as well as the cell death pathways involved. In addition, the effects of LQFM030 on the levels of the p53/MDM2 complex were also carried out using 3T3 cells as a p53 wild-type model.

The novel piperazine-containing compound LQFM018: Necroptosis cell death mechanisms, dopamine D receptor binding and toxicological assessment.

Piperazine is a promising scaffold for drug development due to its broad spectrum of biological activities. Based on this, the new piperazine-containing compound LQFM018 (2) [ethyl 4-((1-(4-chlorophenyl)-1H-pyrazol-4-yl)methyl)piperazine-1-carboxylate] was synthetized and some biological activities investigated. In this work, we described its ability to bind aminergic receptors, antiproliferative effects as well as the LQFM018 (2)-triggered cell death mechanisms, in K562 leukemic cells, by flow cytometric analyses.

LQFM030 reduced Ehrlich ascites tumor cell proliferation and VEGF levels.

Aims: This study reports the biological properties of LQFM030 in vivo, a molecular simplification of the compound nutlin-1.

Main Methods: Ehrlich ascites tumor (EAT)-bearing mice were treated intraperitoneally with LQFM030 (50, 75 or 150mg/kg) for 10days to determine changes in ascites tumor volume, body weight, cytotoxicity and angiogenesis. Moreover, flow cytometric expression of p53 and p21 proteins and caspase-3/7, -8 and -9 activation were investigated in EAT cells from mice treated.

4-Nerolidylcatechol: apoptosis by mitochondrial mechanisms with reduction in cyclin D1 at G0/G1 stage of the chronic myelogenous K562 cell line.

Context: 4-Nerolidylcatechol (4-NRC) has showed antitumor potential through apoptosis. However, its apoptotic mechanisms are still unclear, especially in leukemic cells.

Objectives: To evaluate the cytotoxic potential of 4-NRC and its cell death pathways in p53-null K562 leukemic cells.

A novel chalcone derivative, LQFM064, induces breast cancer cells death via p53, p21, KIT and PDGFRA.

This study shows the design, synthesis and antitumoral potential evaluation of a novel chalcone-like compound, (E)-3- (3, 5-di-ter-butyl-4-hydroxyphenyl)-1- (4-hydroxy-3-methoxyphenyl) prop-2-en-1-one [LQFM064) (4)], against human breast adenocarcinoma MCF7 cells. Some toxicological parameters were also investigated. LQFM064) (4) exhibited cytotoxic activity against MCF7 cells (IC=21μM), in a concentration dependent-manner, and triggered significant changes in cell morphology and biochemical/molecular parameters, which are suggestive of an apoptosis inductor.

Induction of apoptosis in Ehrlich ascites tumour cells via p53 activation by a novel small-molecule MDM2 inhibitor - LQFM030.

Objective: The activation of the p53 pathway through the inhibition of MDM2 has been proposed as a novel therapeutic strategy against tumours. A series of cis-imidazoline analogues, termed nutlins, were reported to displace the recombinant p53 protein from its complex with MDM2 by binding to MDM2 in the p53 pocket, and exhibited an antitumour activity both in vitro and in vivo. Thus, the purpose of this study was to evaluate the antitumour properties of LQFM030 (2), a nutlin analogue created by employing the strategy of molecular simplification.

4-Nerolidylcatechol analogues as promising anticancer agents.

4-Nerolidylcatechol (1) is an isolated compound from Pothomorphe umbellata L. (Piperaceae) with promising antitumor cells properties. However it presents lability under light and room temperatures.

The clinicopathologic significance of the expression of HLA-G in oral squamous cell carcinoma.

Objective: This study aimed to evaluate HLA-G expression in primary oral cavity squamous cell carcinoma (OCSCC) and potentially malignant lesions and to evaluate its relationship with clinicopathologic parameters.

Study Design: HLA-G expression in samples from patients with metastatic and nonmetastatic OCSCC (n = 60), potentially malignant lesions (n = 15), and clinically and histologically normal oral mucosa (n = 10) was characterized by immunohistochemistry. The density of CD8, CD83, and CD68 cells and Ki-67(+) and bcl-2(+) neoplastic cells were analyzed.

4-Nerolidylcatechol and its synthetic analogues: antioxidant activity and toxicity evaluation.

4-Nerolidylcatechol (1) is a secondary metabolite of plants and is described as a promising anti-inflammatory, antimalarial, antiulcerogenic, analgesic and cytotoxic compound possibly due to its antioxidant profile. In this study, we evaluated the pharmacologic activity and the antioxidant and toxicological profiles of compound (1) and its synthetic analogues (2-6). The synthetic analogues were designed from the lead compound, (1), using a molecular-simplification strategy.

Repertoire, genealogy and genomic organization of cruzipain and homologous genes in Trypanosoma cruzi, T. cruzi-like and other trypanosome species.

Trypanosoma cruzi, the agent of Chagas disease, is a complex of genetically diverse isolates highly phylogenetically related to T. cruzi-like species, Trypanosoma cruzi marinkellei and Trypanosoma dionisii, all sharing morphology of blood and culture forms and development within cells. However, they differ in hosts, vectors and pathogenicity: T.

Cysteine proteases of Trypanosoma (Megatrypanum) theileri: cathepsin L-like gene sequences as targets for phylogenetic analysis, genotyping diagnosis.

Although Trypanosomatheileri and allied trypanosomes are the most widespread trypanosomes in bovids little is known about proteolytic enzymes in these species. We have characterized genes encoding for cathepsin L-like (CATL) cysteine proteases from isolates of cattle, water buffalo and deer that largely diverged from homologues of other trypanosome species. Analysis of 78 CATL catalytic domain sequences from 22 T.

Cathepsin L-like genes of Trypanosoma vivax from Africa and South America--characterization, relationships and diagnostic implications.

We characterized sequences from genes encoding cathepsin L-like (CatL-like) cysteine proteases from African and South American isolates of Trypanosoma vivax and T. vivax-like organisms, and evaluated their suitability as genetic markers for population structure analysis and diagnosis. Phylogenetic analysis of sequences corresponding to CatL-like catalytic domains revealed substantial polymorphism, and clades of sequences (TviCatL1-9) were separated by large genetic distances.