DAVID VASQUEZ - Academia.edu (original) (raw)
Papers by DAVID VASQUEZ
The Fourth Annual INTAMS Summer Course
Intams Review, 2003
The Astrophysical Journal, 2013
The detection of E-cyanomethanimine (E-HNCHCN) toward Sagittarius B2(N) is made by comparing the ... more The detection of E-cyanomethanimine (E-HNCHCN) toward Sagittarius B2(N) is made by comparing the publicly available Green Bank Telescope (GBT) PRIMOS survey spectra to laboratory rotational spectra from a reaction product screening experiment. The experiment uses broadband molecular rotational spectroscopy to monitor the reaction products produced in an electric discharge source using a gas mixture of NH 3 and CH 3 CN. Several transition frequency coincidences between the reaction product screening spectra and previously unassigned interstellar rotational transitions in the PRIMOS survey have been assigned to E-cyanomethanimine. A total of eight molecular rotational transitions of this molecule between 9 and 50 GHz are observed with the GBT. E-cyanomethanimine, often called the HCN dimer, is an important molecule in prebiotic chemistry because it is a chemical intermediate in proposed synthetic routes of adenine, one of the two purine nucleobases found in DNA and RNA. New analyses of the rotational spectra of both E-cyanomethanimine and Z-cyanomethanimine that incorporate previous millimeterwave measurements are also reported.
Cancer prevention research (Philadelphia, Pa.), 2010
Exercise has been linked to a reduced cancer risk in animal models. However, the underlying mecha... more Exercise has been linked to a reduced cancer risk in animal models. However, the underlying mechanisms are unclear. This study assessed the impact of exercise with dietary consideration on the phospholipid profile in TPA-induced mouse skin tissues. CD-1 mice were randomly assigned to one of the three groups: ad libitum-fed sedentary control, ad libitum-fed treadmill exercise at 13.4 m/min for 60 min/d, 5 d/wk (Ex+AL), and treadmill exercised but pair-fed with the same amount as the control (Ex+PF). After 14 wks, Ex+PF but not Ex+AL mice demonstrated ~25% decrease in both body weight and body fat when compared to the controls. Of the total 338 phospholipids determined by electrospray ionization tandem mass spectrometry, 57 were significantly changed, and 25 species could distinguish effects of exercise and diet treatments in a stepwise discriminant analysis. A 36-75% decrease of phosphatidylinositol (PI) levels in Ex+PF mice occurred along with a significant reduction of PI3K in TPA-induced skin epidermis, as measured by both western blotting and immunohistochemistry. In addition, near 2-fold increase of the long chain polyunsaturated fatty acids, docosahexaenoic and docosapentaenoic acids, in phosphatidylcholines, phosphatidylethanolamines, and lysophosphatidylethanolamines wasobserved in the Ex+PF group. Microarray analysis indicated that the expression of fatty acid elongase-1 increased. Taken together, these data indicate that exercise with controlled dietary intake but not exercise alone significantly reduced body weight and body fat as well as modified the phospholipid profile, which may contribute to cancer prevention by reducing TPA-induced PI3K and by enhancing ω-3 fatty acid elongation.
Clinical cancer research : an official journal of the American Association for Cancer Research, 2014
Background: Current technology permits an unbiased massive analysis of somatic genetic alteration... more Background: Current technology permits an unbiased massive analysis of somatic genetic alterations from tumor DNA as well as the generation of individualized mouse xenografts (Avatar models). This work aimed to evaluate our experience integrating these two strategies to personalize the treatment of patients with cancer.
Design and synthesis of angucyclinone AB-pyrido[2,3-d] pyrimidine analogues
Tetrahedron Letters, 2008
... Jaime A. Valderrama Corresponding Author Contact Information , a , E-mail The Corresponding A... more ... Jaime A. Valderrama Corresponding Author Contact Information , a , E-mail The Corresponding Author and David Vásquez a. ... Full-size image (11K). Keywords: Quinones; Michael addition; DielsAlder reaction; Regioselectivity. ...
Design and Synthesis of Angucyclinone 5-Aza Analogues
Synlett, 2006
... Design and Synthesis of Angucyclinone 5-Aza Analogues. Jaime A. Valderrama*, M. Florencia Gon... more ... Design and Synthesis of Angucyclinone 5-Aza Analogues. Jaime A. Valderrama*, M. Florencia González, Pamela Colonelli, David Vásquez. ... Key words. Michael additions - quinones - heterocycles - Diels-Alder reactions - regioselectivity. ...
![Research paper thumbnail of Synthesis and Antitumor Evaluation of 6-Aryl-substituted benzo[j]phenanthridine- and Benzo[g]pyrimido[4,5-c]isoquinolinequinones](https://attachments.academia-assets.com/47289364/thumbnails/1.jpg)
](Molecules, 2012
A variety of novel 6-arylsubstituted benzo[j]phenanthridine-and benzo[g]pyrimido[4,5-c]isoquinoli... more A variety of novel 6-arylsubstituted benzo[j]phenanthridine-and benzo[g]pyrimido[4,5-c]isoquinolinequinones were synthesized from 1,4-naphthoquinone, arylaldehydes and enaminones via a two-step synthetic approach. The cytotoxic activity of the aminoquinone derivatives was evaluated in vitro against one normal cell line (MRC-5 lung fibroblasts) and three human cancer cell lines (AGS human gastric adenocarcinoma; SK-MES-1 human lung cancer cells, and J82 human bladder carcinoma) in 72-h drug exposure assays using the MTT colorimetric method. Structure-activity relationships within the series of angular quinones reveal that the insertion of pyrrol-2-yl and furan-2-yl groups at the 6-position is more significant for the increase of the potency and selectivity index of the pharmacophores.
A new method to study permeation of β-lactam antibiotics into reconstituted vesicles from the outer membrane of Pseudomonas aeruginosa NCTC 10662
FEBS Letters, 1982
Cancer, 2014
BACKGROUND: Patients with advanced, metastatic sarcoma have a poor prognosis, and the overall ben... more BACKGROUND: Patients with advanced, metastatic sarcoma have a poor prognosis, and the overall benefit from the few standard-ofcare therapeutics available is small. The rarity of this tumor, combined with the wide range of subtypes, leads to difficulties in conducting clinical trials. The authors previously reported the outcome of patients with a variety of common solid tumors who received treatment with drug regimens that were first tested in patient-derived xenografts using a proprietary method ("TumorGrafts"). METHODS: Tumors resected from 29 patients with sarcoma were implanted into immunodeficient mice to identify drug targets and drugs for clinical use. The results of drug sensitivity testing in the TumorGrafts were used to personalize cancer treatment. RESULTS: Of 29 implanted tumors, 22 (76%) successfully engrafted, permitting the identification of treatment regimens for these patients. Although 6 patients died before the completion of TumorGraft testing, a correlation between TumorGraft results and clinical outcome was observed in 13 of 16 (81%) of the remaining individuals. No patients progressed during the TumorGraft-predicted therapy.
![Research paper thumbnail of Synthesis and antitumor evaluation of 8-phenylaminopyrimido[4,5-c]isoquinolinequinones](https://attachments.academia-assets.com/47289363/thumbnails/1.jpg)
](Bioorganic & Medicinal Chemistry Letters, 2009
A series of 8-phenylaminopyrimido[4,5-c]isoquinoline-7,10-quinone derivatives were prepared by re... more A series of 8-phenylaminopyrimido[4,5-c]isoquinoline-7,10-quinone derivatives were prepared by regioselective amination reaction of pyrimido[4,5-c]isoquinoline-7,10-quinones with arylamines in the presence of a Lewis acid catalyst. Preliminary evaluation of the members of the series against cancer cell lines and assays of activation of their cytotoxic activity on K562 cells with ascorbic acid are reported.
Anti-Cancer Agents in Medicinal Chemistry, 2011
Cancer cells are particularly vulnerable to treatments impairing redox homeostasis. Reactive oxyg... more Cancer cells are particularly vulnerable to treatments impairing redox homeostasis. Reactive oxygen species (ROS) can indeed play an important role in the initiation and progression of cancer, and advanced stage tumors frequently exhibit high basal levels of ROS that stimulate cell proliferation and promote genetic instability. In addition, an inverse correlation between histological grade and antioxidant enzyme activities is frequently observed in human tumors, further supporting the existence of a redox dysregulation in cancer cells. This biochemical property can be exploited by using redox-modulating compounds, which represent an interesting approach to induce cancer cell death. Thus, we have developed a new strategy based on the use of pharmacologic concentrations of ascorbate and redox-active quinones. Ascorbate-driven quinone redox cycling leads to ROS formation and provokes an oxidative stress that preferentially kills cancer cells and spares healthy tissues. Cancer cell death occurs through necrosis and the underlying mechanism implies an energetic impairment (ATP depletion) that is likely due to glycolysis inhibition. Additional mechanisms that participate to cell death include calcium equilibrium impairment and oxidative cleavage of protein chaperone Hsp90. Given the low systemic toxicity of ascorbate and the impairment of crucial survival pathways when associated with redox-active quinones, these combinations could represent an original approach that could be combined to standard cancer therapy.
The Fourth Annual INTAMS Summer Course
Intams Review, 2003
The Astrophysical Journal, 2013
The detection of E-cyanomethanimine (E-HNCHCN) toward Sagittarius B2(N) is made by comparing the ... more The detection of E-cyanomethanimine (E-HNCHCN) toward Sagittarius B2(N) is made by comparing the publicly available Green Bank Telescope (GBT) PRIMOS survey spectra to laboratory rotational spectra from a reaction product screening experiment. The experiment uses broadband molecular rotational spectroscopy to monitor the reaction products produced in an electric discharge source using a gas mixture of NH 3 and CH 3 CN. Several transition frequency coincidences between the reaction product screening spectra and previously unassigned interstellar rotational transitions in the PRIMOS survey have been assigned to E-cyanomethanimine. A total of eight molecular rotational transitions of this molecule between 9 and 50 GHz are observed with the GBT. E-cyanomethanimine, often called the HCN dimer, is an important molecule in prebiotic chemistry because it is a chemical intermediate in proposed synthetic routes of adenine, one of the two purine nucleobases found in DNA and RNA. New analyses of the rotational spectra of both E-cyanomethanimine and Z-cyanomethanimine that incorporate previous millimeterwave measurements are also reported.
Cancer prevention research (Philadelphia, Pa.), 2010
Exercise has been linked to a reduced cancer risk in animal models. However, the underlying mecha... more Exercise has been linked to a reduced cancer risk in animal models. However, the underlying mechanisms are unclear. This study assessed the impact of exercise with dietary consideration on the phospholipid profile in TPA-induced mouse skin tissues. CD-1 mice were randomly assigned to one of the three groups: ad libitum-fed sedentary control, ad libitum-fed treadmill exercise at 13.4 m/min for 60 min/d, 5 d/wk (Ex+AL), and treadmill exercised but pair-fed with the same amount as the control (Ex+PF). After 14 wks, Ex+PF but not Ex+AL mice demonstrated ~25% decrease in both body weight and body fat when compared to the controls. Of the total 338 phospholipids determined by electrospray ionization tandem mass spectrometry, 57 were significantly changed, and 25 species could distinguish effects of exercise and diet treatments in a stepwise discriminant analysis. A 36-75% decrease of phosphatidylinositol (PI) levels in Ex+PF mice occurred along with a significant reduction of PI3K in TPA-induced skin epidermis, as measured by both western blotting and immunohistochemistry. In addition, near 2-fold increase of the long chain polyunsaturated fatty acids, docosahexaenoic and docosapentaenoic acids, in phosphatidylcholines, phosphatidylethanolamines, and lysophosphatidylethanolamines wasobserved in the Ex+PF group. Microarray analysis indicated that the expression of fatty acid elongase-1 increased. Taken together, these data indicate that exercise with controlled dietary intake but not exercise alone significantly reduced body weight and body fat as well as modified the phospholipid profile, which may contribute to cancer prevention by reducing TPA-induced PI3K and by enhancing ω-3 fatty acid elongation.
Clinical cancer research : an official journal of the American Association for Cancer Research, 2014
Background: Current technology permits an unbiased massive analysis of somatic genetic alteration... more Background: Current technology permits an unbiased massive analysis of somatic genetic alterations from tumor DNA as well as the generation of individualized mouse xenografts (Avatar models). This work aimed to evaluate our experience integrating these two strategies to personalize the treatment of patients with cancer.
Design and synthesis of angucyclinone AB-pyrido[2,3-d] pyrimidine analogues
Tetrahedron Letters, 2008
... Jaime A. Valderrama Corresponding Author Contact Information , a , E-mail The Corresponding A... more ... Jaime A. Valderrama Corresponding Author Contact Information , a , E-mail The Corresponding Author and David Vásquez a. ... Full-size image (11K). Keywords: Quinones; Michael addition; DielsAlder reaction; Regioselectivity. ...
Design and Synthesis of Angucyclinone 5-Aza Analogues
Synlett, 2006
... Design and Synthesis of Angucyclinone 5-Aza Analogues. Jaime A. Valderrama*, M. Florencia Gon... more ... Design and Synthesis of Angucyclinone 5-Aza Analogues. Jaime A. Valderrama*, M. Florencia González, Pamela Colonelli, David Vásquez. ... Key words. Michael additions - quinones - heterocycles - Diels-Alder reactions - regioselectivity. ...
Molecules, 2012
A variety of novel 6-arylsubstituted benzo[j]phenanthridine-and benzo[g]pyrimido[4,5-c]isoquinoli... more A variety of novel 6-arylsubstituted benzo[j]phenanthridine-and benzo[g]pyrimido[4,5-c]isoquinolinequinones were synthesized from 1,4-naphthoquinone, arylaldehydes and enaminones via a two-step synthetic approach. The cytotoxic activity of the aminoquinone derivatives was evaluated in vitro against one normal cell line (MRC-5 lung fibroblasts) and three human cancer cell lines (AGS human gastric adenocarcinoma; SK-MES-1 human lung cancer cells, and J82 human bladder carcinoma) in 72-h drug exposure assays using the MTT colorimetric method. Structure-activity relationships within the series of angular quinones reveal that the insertion of pyrrol-2-yl and furan-2-yl groups at the 6-position is more significant for the increase of the potency and selectivity index of the pharmacophores.
A new method to study permeation of β-lactam antibiotics into reconstituted vesicles from the outer membrane of Pseudomonas aeruginosa NCTC 10662
FEBS Letters, 1982
Cancer, 2014
BACKGROUND: Patients with advanced, metastatic sarcoma have a poor prognosis, and the overall ben... more BACKGROUND: Patients with advanced, metastatic sarcoma have a poor prognosis, and the overall benefit from the few standard-ofcare therapeutics available is small. The rarity of this tumor, combined with the wide range of subtypes, leads to difficulties in conducting clinical trials. The authors previously reported the outcome of patients with a variety of common solid tumors who received treatment with drug regimens that were first tested in patient-derived xenografts using a proprietary method ("TumorGrafts"). METHODS: Tumors resected from 29 patients with sarcoma were implanted into immunodeficient mice to identify drug targets and drugs for clinical use. The results of drug sensitivity testing in the TumorGrafts were used to personalize cancer treatment. RESULTS: Of 29 implanted tumors, 22 (76%) successfully engrafted, permitting the identification of treatment regimens for these patients. Although 6 patients died before the completion of TumorGraft testing, a correlation between TumorGraft results and clinical outcome was observed in 13 of 16 (81%) of the remaining individuals. No patients progressed during the TumorGraft-predicted therapy.
Bioorganic & Medicinal Chemistry Letters, 2009
A series of 8-phenylaminopyrimido[4,5-c]isoquinoline-7,10-quinone derivatives were prepared by re... more A series of 8-phenylaminopyrimido[4,5-c]isoquinoline-7,10-quinone derivatives were prepared by regioselective amination reaction of pyrimido[4,5-c]isoquinoline-7,10-quinones with arylamines in the presence of a Lewis acid catalyst. Preliminary evaluation of the members of the series against cancer cell lines and assays of activation of their cytotoxic activity on K562 cells with ascorbic acid are reported.
Anti-Cancer Agents in Medicinal Chemistry, 2011
Cancer cells are particularly vulnerable to treatments impairing redox homeostasis. Reactive oxyg... more Cancer cells are particularly vulnerable to treatments impairing redox homeostasis. Reactive oxygen species (ROS) can indeed play an important role in the initiation and progression of cancer, and advanced stage tumors frequently exhibit high basal levels of ROS that stimulate cell proliferation and promote genetic instability. In addition, an inverse correlation between histological grade and antioxidant enzyme activities is frequently observed in human tumors, further supporting the existence of a redox dysregulation in cancer cells. This biochemical property can be exploited by using redox-modulating compounds, which represent an interesting approach to induce cancer cell death. Thus, we have developed a new strategy based on the use of pharmacologic concentrations of ascorbate and redox-active quinones. Ascorbate-driven quinone redox cycling leads to ROS formation and provokes an oxidative stress that preferentially kills cancer cells and spares healthy tissues. Cancer cell death occurs through necrosis and the underlying mechanism implies an energetic impairment (ATP depletion) that is likely due to glycolysis inhibition. Additional mechanisms that participate to cell death include calcium equilibrium impairment and oxidative cleavage of protein chaperone Hsp90. Given the low systemic toxicity of ascorbate and the impairment of crucial survival pathways when associated with redox-active quinones, these combinations could represent an original approach that could be combined to standard cancer therapy.