Search

Your search keyword '"Diaz, J Fernando"' showing total 39 results
Start Over Author "Diaz, J Fernando"
39 results on '"Diaz, J Fernando"'

1. Modulation of taxane binding to tubulin curved and straight conformations by systematic 3′N modification provides for improved microtubule binding, persistent cytotoxicity and in vivo potency

Author

Ma, Yuntao, Josa-Prado, Fernando, Essif, Jacob Nathaniel, Liu, Shuqi, Li, Shuo, Lucena-Agell, Daniel, Chan, Peter YW., Goossens, Kenneth, Hortigüela, Rafael, Matesanz, Ruth, Wang, Yingjie, Gago, Federico, Wang, Hongbo, Risinger, April, Diaz, J. Fernando, and Fang, Wei-Shuo

Published
2023
Full Text
View/download PDF

4. Design and synthesis of multifunctional microtubule targeting agents endowed with dual pro-apoptotic and anti-autophagic efficacy

Author

Campiani, Giuseppe, Khan, Tuhina, Ulivieri, Cristina, Staiano, Leopoldo, Papulino, Chiara, Magnano, Stefania, Nathwani, Seema, Ramunno, Anna, Lucena-Agell, Daniel, Relitti, Nicola, Federico, Stefano, Pozzetti, Luca, Carullo, Gabriele, Casagni, Alice, Brogi, Simone, Vanni, Francesca, Galatello, Paola, Ghanim, Magda, McCabe, Niamh, Lamponi, Stefania, Valoti, Massimo, Ibrahim, Ola, O'Sullivan, Jeffrey, Turkington, Richard, Kelly, Vincent P., VanWemmel, Ruben, Díaz, J. Fernando, Gemma, Sandra, Zisterer, Daniela, Altucci, Lucia, De Matteis, Maria Antonietta, Butini, Stefania, and Benedetti, Rosaria

Published
2022
Full Text
View/download PDF

6. Structure-activity relationships, biological evaluation and structural studies of novel pyrrolonaphthoxazepines as antitumor agents

Author

Brindisi, Margherita, Ulivieri, Cristina, Alfano, Gloria, Gemma, Sandra, de Asís Balaguer, Francisco, Khan, Tuhina, Grillo, Alessandro, Chemi, Giulia, Menchon, Grégory, Prota, Andrea E., Olieric, Natacha, Lucena-Agell, Daniel, Barasoain, Isabel, Diaz, J. Fernando, Nebbioso, Angela, Conte, Mariarosaria, Lopresti, Ludovica, Magnano, Stefania, Amet, Rebecca, Kinsella, Paula, Zisterer, Daniela M., Ibrahim, Ola, O'Sullivan, Jeff, Morbidelli, Lucia, Spaccapelo, Roberta, Baldari, Cosima, Butini, Stefania, Novellino, Ettore, Campiani, Giuseppe, Altucci, Lucia, Steinmetz, Michel O., and Brogi, Simone

Published
2019
Full Text
View/download PDF

9. Tannic Acid and Ethyl Gallate Potentialize Paclitaxel Effect on Microtubule Dynamics in Hep3B Cells

Author

Sánchez-Carranza, Jessica Nayelli, Redondo-Horcajo, Mariano, Barasoain, Isabel, Escobar-Aguilar, Ever Angel, Millán-Pacheco, César, Alvarez, Laura, Salas Vidal, Enrique, Diaz, J. Fernando, Gonzalez-Maya, Leticia, Sánchez-Carranza, Jessica Nayelli, Redondo-Horcajo, Mariano, Barasoain, Isabel, Escobar-Aguilar, Ever Angel, Millán-Pacheco, César, Alvarez, Laura, Salas Vidal, Enrique, Diaz, J. Fernando, and Gonzalez-Maya, Leticia

Abstract

Among broad-spectrum anticancer agents, paclitaxel (PTX) has proven to be one of the most effective against solid tumors for which more specific treatments are lacking. However, drawbacks such as neurotoxicity and the development of resistance reduce its therapeutic efficacy. Therefore, there is a need for compounds able to improve its activity by synergizing with it or potentiating its effect, thus reducing the doses required. We investigated the interaction between PTX and tannins, other compounds with anticancer activity known to act as repressors of several proteins involved in oncological pathways. We found that both tannic acid (TA) and ethyl gallate (EG) strongly potentiate the toxicity of PTX in Hep3B cells, suggesting their utility in combination therapy. We also found that AT and EG promote tubulin polymerization and enhance the effect of PTX on tubulin, suggesting a direct interaction with tubulin. Biochemical experiments confirmed that TA, but not EG, binds tubulin and potentiates the apparent binding affinity of PTX for the tubulin binding site. Furthermore, the molecular docking of TA to tubulin suggests that TA can bind to two different sites on tubulin, one at the PTX site and the second at the interface of α and β-tubulin (cluster 2). The binding of TA to cluster 2 could explain the overstabilization in the tubulin + PTX combinatorial assay. Finally, we found that EG can inhibit PTX-induced expression of pAkt and pERK defensive protein kinases, which are involved in resistance to PXT, by limiting cell death (apoptosis) and favoring cell proliferation and cell cycle progression. Our results support that tannic acid and ethyl gallate are potential chemotherapeutic agents due to their potentiating effect on paclitaxel.

Published
2023

17. NMR determination of the bioactive conformation of Peloruside A bound to microtubules

Author

Jimenez-Barbero, Jesus, Canales, Angeles, Northcole, Peter T., Buey, Ruben, M., Andreu, Jose Manuel, and Diaz, J. Fernando

Subjects
Microtubules -- Structure, Conformational analysis -- Methods, Nuclear magnetic resonance -- Analysis, Chemistry
Abstract

The determination of the conformation of Peloruside A bound to biochemically stabilized microtubes is reported. A model of the binding mode to tublin is proposed, by docking the bioactive conformation of Peloruside, which involves the [alpha]-tublin monomer, in contrast with taxol, which binds to the [beta]-monomer.

Published
2006

18. Au@p4VP core@shell pH-sensitive nanocomposites suitable for drug entrapment

Author

Clara-Rahola, Joaquim, primary, Moscoso, Ana, additional, Belén Ruiz-Muelle, Ana, additional, Laurenti, Marco, additional, Formanek, Petr, additional, Lopez-Romero, Juan M., additional, Fernández, Ignacio, additional, Diaz, J. Fernando, additional, Rubio-Retama, Jorge, additional, Fery, Andreas, additional, and Contreras-Cáceres, Rafael, additional

Published
2018
Full Text
View/download PDF

19. Insights into nucleotide recognition by cell division protein FtsZ from a mant-GTP competition assay and molecular dynamics

Author

Schaffner-Barbero, Claudia, Gil-Redondo, Ruben, Ruiz-Avila, Laura B., Huecas, Sonia, Lappchen, Tilman, Blaauwen, Tanneke den, Diaz, J. Fernando, Morreale, Antonio, and Andreu, Jose M.

Subjects
Fluorescence -- Analysis, G proteins -- Chemical properties, G proteins -- Structure, G proteins -- Optical properties, Protein binding -- Analysis, Biological sciences, Chemistry
Abstract

A new homogeneous competition assay developed by employing the fluorescence anisotropy change of mant-GTP upon binding to nucleotide-free FtsZ is used to determine the apparent contributions of the guanine, ribose, and the [alpha]-, [beta]-, and [gamma]-phosphates to the free energy change of nucleotide binding. The results offer insight into the FtsZ-nucleotide interactions, which could be useful in the rational design of new inhibitors, especially GTP phosphate mimetics.

Published
2010

20. The nucleotide switch of tubulin and microtubule assembly: A polymerization-driven structural change

Author

Buey, Ruben M., Diaz, J. Fernando, and Andreu, Jose M.

Subjects
Nucleotides -- Research, Polymerization -- Analysis, Tubulins -- Research, Biological sciences, Chemistry
Abstract

A conserved structural switch between the active and inactive states is extracted from tubulin and FtsZ structures and it offers a new biochemical explanation for the nucleotide regulation of their assembly. The analysis has shown that the unassembled tubulin-GTP is in the inactive, curved conformation as in tubulin-GDP rings and it is driven into the straight microtubule conformation by the assembly contacts, whereas the GTP gamma-phosphate lowers the free energy difference between the curved and straight forms.

Published
2006

21. Cyclostreptin (FR182877), an antitumor tubulin-polymerizing agent deficient in enhancing tubulin assembly despite its affinity for the taxoid site

Author

Edler, Micheal C., Buey, Ruben M., Gussio, Rick, Marcus, Adam I., Vanderwal, Christopher D., Sorensen, Erik J., Diaz, J. Fernando, Giannakakou, Paraskevi, and Hamel, Ernest

Subjects
Tubulins -- Structure, Tubulins -- Research, Polymers -- Research, Biological sciences, Chemistry
Abstract

The interaction of cyclostreptin with tubulin polymer by examining its effects on the binding of the fluorescent paclitaxel analogue Flutax-2 to glutaraldehyde-fixed microtubules is explored. Compared with paclitaxel and docetaxel, cyclostreptin had decreased affinity for polymer at 4 degree Celsius but not at 35 degree Celsius.

Published
2005

35. Asymptomatic and Symptomatic Cryptosporidiosis: Their Acute Effect on Weight Gain in Peruvian Children.

Author

Checkley, William, Gilman, Robert H., Epstein, Leonardo D., Suarez, Manuel, Diaz, J. Fernando, Cabrera, Lilia, Black, Robert E., and Sterling, Charles R.

Subjects
CRYPTOSPORIDIOSIS, WEIGHT gain, CRYPTOSPORIDIUM parvum, DIARRHEA in infants, NUTRITION disorders, PHYSIOLOGY, DISEASE risk factors
Abstract

This study investigated whether a child's first infection with Cryptosporidium parvum had an acute effect on weight gain. Specifically, the authors compared monthly rates of weight gain between C. parvum-infected and noninfected children. Over a 2-year period (1989–1991), a cohort of Peruvian children aged 0–3 months at recruitment were followed twice weekly for assessment of daily diarrheal status, weekly for C. parvum stool examinations, and monthly for anthropometric measurements. Data on 207 children permitted the authors to examine the effect of C. parvum infection on weight gain. During the 2-year study period, 45% (94/207) of the children became infected with C. parvum for the first time. Weight gain intervals in 57 of the 94 infected children met criteria for analysis. Of these, 63 percent (36/57) were asymptomatic (i.e., had no diarrhea). On average, children with symptomatic cryptosporidiosis gained (i.e., grew) 342 g less (95% confidence interval 167–517) during the first month of infection than did children without diarrhea who were not yet infected. The effect of asymptomatic cryptosporidiosis was less severe: On average, children with asymptomatic infection gained 162 g less (95% confidence interval 27–297) during the first month of infection than did children without diarrhea who were not yet infected. Symptomatic cryptosporidiosis retarded weight gain more than did asymptomatic cryptosporidiosis, but the latter was twice as common. Since asymptomatic cryptosporidiosis is more prevalent, it may have more of an overall adverse effect on child growth in the community than symptomatic cryptosporidiosis. Am J Epidemiol 1997; 145: 156–63. [ABSTRACT FROM AUTHOR]

Published
1997
Full Text
View/download PDF

36. Improved Recognition of Leukoaraiosis and Cognitive Impairment in Alzheimer's Disease

Author

Diaz, J. Fernando, Merskey, Harold, Hachinski, Vladimir C., Lee, Donald H., Boniferro, Mary, Wong, Cindy J., Mirsen, Thomas R., and Fox, Hannah

Abstract

• We identified 85 patients in a longitudinal study of dementia who had uncomplicated Alzheimer's disease and in whom computed tomography of the head and psychometric testing were conducted within a 6-month period following their entry into the study. Thirty-four patients (40%) had leukoaraiosis, which was disproportionately common in female patients (62% vs 15% in male patients). Analysis of covariance demonstrated a relative reduction of scores on the Extended Scale for Dementia in those patients who had leukoaraiosis, after adjusting for the confounding effects of age, sex, educational level, and duration of illness. Leukoaraiosis was also much more common in women, even after adjusting for the possible confounding effects of age, duration of illness, Extended Scale for Dementia score, and hypertension. Multiple regression analysis showed that leukoaraiosis accounted for 11.6% of the variance of the Extended Scale for Dementia scores. Leukoaraiosis, together with duration of illness, accounted for 18.2% of the variance. Leukoaraiosis is associated with a greater degree of cognitive impairment in patients with Alzheimer's disease.

Published
1991
Full Text
View/download PDF

37. Clinical Correlates of White-Matter Changes on Magnetic Resonance Imaging Scans of the Brain

Author

Mirsen, Thomas R., Lee, Donald H., Wong, Cindy J., Diaz, J. Fernando, Fox, Allan J., Hachinski, Vladimir C., and Merskey, Harold

Abstract

• We report our observations on the clinical and radiologic correlates of changes in cerebral white matter based on 94 subjects undergoing magnetic resonance imaging in a prospective study of dementia. Periventricular hyperintensity occurred twice as often in patients with Alzheimer's disease as in healthy control subjects. Within the control group, the presence of periventricular hyperintensity correlated significantly with one measure of cerebral atrophy and with the presence of changes in the adjoining deep white matter. The significance of white-matter changes distinct from the ventricles (leuko-araiosis) remains unsettled. Leuko-araiosis on the magnetic resonance imaging scan, unlike its correlate on the computed tomographic scan, was not shown to relate to cognitive decline or to the presence of focal abnormalities on neurologic examination. This is likely to reflect the heterogeneity of the changes detected with magnetic resonance imaging and their limited extent in our subjects.

Published
1991
Full Text
View/download PDF

39. Structure-activity relationships, biological evaluation and structural studies of novel pyrrolonaphthoxazepines as antitumor agents

Author

Grégory Menchon, Lucia Altucci, Giulia Chemi, Simone Brogi, Michel O. Steinmetz, Angela Nebbioso, Natacha Olieric, Daniela M. Zisterer, Francisco de Asís Balaguer, Stefania Butini, Rebecca Amet, Cristina Ulivieri, Alessandro Grillo, Jeff O'Sullivan, Isabel Barasoain, Margherita Brindisi, J. Fernando Díaz, Ettore Novellino, Roberta Spaccapelo, Daniel Lucena-Agell, Ludovica Lopresti, Andrea E. Prota, Sandra Gemma, Mariarosaria Conte, Stefania Magnano, Cosima T. Baldari, Gloria Alfano, Giuseppe Campiani, Paula Kinsella, Tuhina Khan, Lucia Morbidelli, Ola Ibrahim, Brindisi, M, Ulivieri, C, Alfano, G, Gemma, S, de Asís Balaguer, F, Khan, T, Grillo, A, Chemi, G, Menchon, G, Prota, Ae, Olieric, N, Lucena-Agell, D, Barasoain, I, Diaz, Jf, Nebbioso, A, Conte, M, Lopresti, L, Magnano, S, Amet, R, Kinsella, P, Zisterer, Dm, Ibrahim, O, O'Sullivan, J, Morbidelli, L, Spaccapelo, R, Baldari, C, Butini, S, Novellino, E, Campiani, G, Altucci, L, Steinmetz, Mo, Brogi, S., Swiss National Science Foundation, Ministerio de Economía y Competitividad (España), European Commission, Ministero dell'Istruzione, dell'Università e della Ricerca, Brindisi, Margherita, Ulivieri, Cristina, Alfano, Gloria, Gemma, Sandra, de Asís Balaguer, Francisco, Khan, Tuhina, Grillo, Alessandro, Chemi, Giulia, Menchon, Grégory, Prota, Andrea E, Olieric, Natacha, Lucena-Agell, Daniel, Barasoain, Isabel, Diaz, J Fernando, Nebbioso, Angela, Conte, Mariarosaria, Lopresti, Ludovica, Magnano, Stefania, Amet, Rebecca, Kinsella, Paula, Zisterer, Daniela M, Ibrahim, Ola, O'Sullivan, Jeff, Morbidelli, Lucia, Spaccapelo, Roberta, Baldari, Cosima, Butini, Stefania, Novellino, Ettore, Campiani, Giuseppe, Altucci, Lucia, and Steinmetz, Michel O

Subjects
Antitumor agents, Apoptosis, Microtubule-targeting agent, Molecular modeling, Tubulin, X-ray crystallography, Antineoplastic Agents, Cell Cycle, Cell Differentiation, Cell Line, Tumor, Drug Resistance, Multiple, Drug Screening Assays, Antitumor, Humans, Microtubules, Molecular Structure, Oxazepines, Structure-Activity Relationship, Pharmacology, Drug Discovery3003 Pharmaceutical Science, Organic Chemistry, Cellular differentiation, Drug Resistance, Drug Screening Assays, 01 natural sciences, Cancer, epigenetics, Drug Discovery, 0303 health sciences, Tumor, Chemistry, General Medicine, Cell cycle, 3. Good health, medicine.symptom, Multiple, Computational biology, Cell Line, 03 medical and health sciences, medicine, Structure–activity relationship, Mode of action, 030304 developmental biology, 010405 organic chemistry, Antitumor agent, Apoptosi, Antitumor, 0104 chemical sciences, Multiple drug resistance, Mechanism of action, Cell culture, Cancer cell
Abstract

Microtubule-targeting agents (MTAs) are a class of clinically successful anti-cancer drugs. The emergence of multidrug resistance to MTAs imposes the need for developing new MTAs endowed with diverse mechanistic properties. Benzoxazepines were recently identified as a novel class of MTAs. These anticancer agents were thoroughly characterized for their antitumor activity, although, their exact mechanism of action remained elusive. Combining chemical, biochemical, cellular, bioinformatics and structural efforts we developed improved pyrrolonaphthoxazepines antitumor agents and their mode of action at the molecular level was elucidated. Compound 6j, one of the most potent analogues, was confirmed by X-ray as a colchicine-site MTA. A comprehensive structural investigation was performed for a complete elucidation of the structure-activity relationships. Selected pyrrolonaphthoxazepines were evaluated for their effects on cell cycle, apoptosis and differentiation in a variety of cancer cells, including multidrug resistant cell lines. Our results define compound 6j as a potentially useful optimized hit for the development of effective compounds for treating drug-resistant tumors., This work was supported in part by a grant from the Swiss National Science Foundation (31003A_166608; to M.O.S), grant BFU2016-75319-R (AEI/FEDER, EU) from Ministerio de Economia y Competitividad, Blueprint 282510, AIRC-17217. The authors acknowledge networking contribution by the COST Action CM1407 “Challenging organic syntheses inspired by nature - from natural products chemistry to drug discovery” (to M.O.S. and J.F.D.) and the COST Action EPICHEMBIO CM-1406 (to L.A. and G.C.). This work has also received partial funding from the European Union’s Horizon 2020 (EU) research and innovation programme under the Marie Sklodowska-Curie grant agreement No 721906. Finally, this work was partially funded by MIUR-PRIN project n. 2015Y3C5KP (to L.M.).

Published
2019

Catalog

Books, media, physical & digital resources
See catalog results