Publicaciones 2011-2020

@article{RN387,
title = {Telomerase Inhibition by a New Synthetic Derivative of the Aporphine Alkaloid Boldine},
author = { S.K. Noureini and M. Kheirabadi and F. Masoumi and F. Khosrogerdi and Y. Zarei and C. Suarez-Rozas and J. Salas-Norambuena and B.K. Cassels},
url = {/brokenurl#<Go to ISI>://WOS:000434978700318},
doi = {10.3390/ijms19041239},
issn = {1422-0067},
year = {2018},
date = {2018-01-01},
journal = {International Journal of Molecular Sciences},
volume = {19},
number = {4},
abstract = {Telomerase, the enzyme responsible for cell immortality, is an important target in anti-cancer drug discovery. Boldine, an abundant aporphine alkaloid of Peumus boldus, is known to inhibit telomerase at non-toxic concentrations. Cytotoxicity of N-benzylsecoboldine hydrochloride (BSB), a synthetic derivative of boldine, was determined using the MTT method in MCF7 and MDA-MB231 cells. Aliquots of cell lysates were incubated with various concentrations of BSB in qTRAP (quantitative telomere repeat amplification protocol)-ligand experiments before substrate elongation by telomerase or amplification by hot-start Taq polymerase. The crystal structure of TERT, the catalytic subunit of telomerase from Tribolium castaneum, was used for docking and molecular dynamics analysis. The qTRAP-ligand data gave an IC50 value of about 0.17 +/- 0.1 mu M for BSB, roughly 400 times stronger than boldine, while the LD50 in the cytotoxicity assays were 12.5 and 21.88 mu M, respectively, in cells treated for 48 h. Although both compounds interacted well with the active site, MD analysis suggests a second binding site with which BSB interacts via two hydrogen bonds, much more strongly than boldine. Theoretical analyses also evaluated the IC50 for BSB as submicromolar. BSB, with greater hydrophobicity and flexibility than boldine, represents a promising structure to inhibit telomerase at non-toxic concentrations.},
keywords = {apoptosis, assay binding boldine, cells, derivative, domain, inhibition, n-benzylsecoboldine, site, stress, telomerase},
pubstate = {published},
tppubtype = {article}
}

@article{RN242,
title = {Iron Chelators and Antioxidants Regenerate Neuritic Tree and Nigrostriatal Fibers of Mpp Plus /Mptp-Lesioned Dopaminergic Neurons},
author = { P. Aguirre and N.P. Mena and C.M. Carrasco and Y. Munoz and P. Perez-Henriquez and R.A. Morales and B.K. Cassels and C. Mendez-Galvez and O. Garcia-Beltran and C. Gonz\'{a}lez-Billault and M. Nunez},
url = {/brokenurl#<Go to ISI>://WOS:000366715900118},
doi = {10.1371/journal.pone.0144848},
issn = {1932-6203},
year = {2015},
date = {2015-01-01},
journal = {Plos One},
volume = {10},
number = {12},
abstract = {Neuronal death in Parkinson's disease (PD) is often preceded by axodendritic tree retraction and loss of neuronal functionality. The presence of non-functional but live neurons opens therapeutic possibilities to recover functionality before clinical symptoms develop. Considering that iron accumulation and oxidative damage are conditions commonly found in PD, we tested the possible neuritogenic effects of iron chelators and antioxidant agents. We used three commercial chelators: DFO, deferiprone and 2.2'-dypyridyl, and three 8-hydroxyquinoline-based iron chelators: M30, 7MH and 7DH, and we evaluated their effects in vitro using a mesencephalic cell culture treated with the Parkinsonian toxin MPP+ and in vivo using the MPTP mouse model. All chelators tested promoted the emergence of new tyrosine hydroxylase (TH)-positive processes, increased axodendritic tree length and protected cells against lipoperoxidation. Chelator treatment resulted in the generation of processes containing the presynaptic marker synaptophysin. The antioxidants N-acetylcysteine and dymetylthiourea also enhanced axodendritic tree recovery in vitro, an indication that reducing oxidative tone fosters neuritogenesis in MPP+-damaged neurons. Oral administration to mice of the M30 chelator for 14 days after MPTP treatment resulted in increased TH- and GIRK2-positive nigra cells and nigrostriatal fibers. Our results support a role for oral iron chelators as good candidates for the early treatment of PD, at stages of the disease where there is axodendritic tree retraction without neuronal death.},
keywords = {apoptosis, degeneration, dendritic disease, expression, induced models, neurodegeneration, protein, restoration substantia-nigra, tree},
pubstate = {published},
tppubtype = {article}
}

@article{RN266,
title = {Heterocyclic Curcumin Derivatives of Pharmacological Interest: Recent Progress},
author = { M. Martinez-Cifuentes and B. Weiss-Lopez and L.S. Santos and R. Araya-Maturana},
url = {/brokenurl#<Go to ISI>://WOS:000355570800003},
doi = {10.2174/1568026615666150427111837},
issn = {1568-0266},
year = {2015},
date = {2015-01-01},
journal = {Current Topics in Medicinal Chemistry},
volume = {15},
number = {17},
pages = {1663-1672},
abstract = {Curcumin, a natural yellow polyphenol, is isolated from the herb Curcuma longa L. (turmeric), a member of the ginger family. It has been extensively studied due to their multiple pharmacological properties. Nevertheless, curcumin has disadvantages such as poor water solubility, poor bioavailability and rapid metabolism, which has prompted the search for analogues that overcome these shortcomings while maintaining or improving their good pharmacological properties. Among the main curcumin analogues that have been developed, the heterocyclic curcuminoids show a high interest. In this review, we describe recent progress in the synthesis and pharmacological properties of new heterocyclic curcumin derivatives. The most recent developments in anti-cancer, anti-Alzheimer, anti-bacterial and anti-oxidants heterocyclic curcumin derivatives are covered.},
keywords = {alzheimer, analogs, antibacterial, antiinflammatory antioxidant, antioxidants, apoptosis, bioavailability, cancer, curcumin, cytotoxicity, heterocycles, in-vitro, inhibitors molecular properties, targets},
pubstate = {published},
tppubtype = {article}
}

@article{RN156,
title = {Mitochondria: A Promising Target for Anticancer Alkaloids},
author = { F.A. Urra and M. Cordova-Delgado and H. Pessoa-Mahana and O. Ramirez-Rodriguez and B. Weiss-Lopez and J. Ferreira and R. Araya-Maturana},
url = {/brokenurl#<Go to ISI>://WOS:000324801300007},
issn = {1568-0266},
year = {2013},
date = {2013-01-01},
journal = {Current Topics in Medicinal Chemistry},
volume = {13},
number = {17},
pages = {2171-2183},
abstract = {A great number of alkaloids exhibit high potential in cancer research. Some of them are anticancer drugs with well-defined clinical uses, exerting their action on microtubules dynamics or DNA replication and topology. On the other hand, mitochondria have been recognized as an essential organelle in the establishment of tumor characteristics, especially the resistance to cell death, high proliferative capacity and adaptation to unfavorable cellular environment. Interestingly, many alkaloids exert their anticancer activities affecting selectively some functions of the tumor mitochondria by 1) modulating OXPHOS and ADP/ATP transport, 2) increasing ROS levels and mitochondrial potential dissipation by crosstalk between endoplasmic reticulum (ER) and mitochondria, 3) inducing mitochondria-dependent apoptosis and autophagy, 4) inhibiting mitochondrial metabolic pathways and 5) by alteration of the morphology and biogenesis of this organelle. These antecedents show the relevance of developing research about the effects of alkaloids on functions controlled by tumor mitochondria, offering an attractive target for the design of new alkaloid derivatives, considering organelle-specific delivery strategies. This review describes mitochondria as a central component in the anticancer action of a set of alkaloids, in a way to illustrate the importance of this organelle in medicinal chemistry.},
keywords = {alkaloids, apoptosis, cancer capsaicin carbazole caspase-dependent cells, delivery, endoplasmic endoplasmic-reticulum hepatocellular-carcinoma, human induces melanoma-cells microtubule-modulating mitochondria, mouse nucleotide peptide, prostate-cancer reticulum, self-assembling stress, targeting, translocase},
pubstate = {published},
tppubtype = {article}
}