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449 results on '"Cassera, Maria A."'

1. Antimalarial Natural Products

Author

Kingston, David G. I., Cassera, Maria Belen, Kinghorn, A. Douglas, Series Editor, Falk, Heinz, Series Editor, Gibbons, Simon, Series Editor, Asakawa, Yoshinori, Series Editor, Liu, Ji-Kai, Series Editor, Dirsch, Verena M., Series Editor, Appendino, Giovanni, Advisory Editor, Berlinck, Roberto G. S., Advisory Editor, Kobayashi, Jun'ichi, Advisory Editor, Ludwiczuk, Agnieszka, Advisory Editor, Naman, C. Benjamin, Advisory Editor, Mata, Rachel, Advisory Editor, Oberlies, Nicholas H., Advisory Editor, Tasdemir, Deniz, Advisory Editor, Trauner, Dirk, Advisory Editor, Viljoen, Alvaro, Advisory Editor, and Ye, Yang, Advisory Editor

Published
2022
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9. Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond.

Author

Van Voorhis, Wesley C, Adams, John H, Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H, Alano, Pietro, Alday, Aintzane, Alemán Resto, Yesmalie, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T, Avery, Simon V, Avery, Vicky M, Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Jürgen, Boucher, Lauren E, Boyom, Fabrice F, Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R, Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Belen Cassera, Maria, Chih-Chien Cheng, Ken, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L, Colón-López, Daisy D, Corbett, Yolanda, Crowther, Gregory J, Cowan, Noemi, D'Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L, Du, Alan Y, Duffy, Sandra, Abd El-Salam El-Sayed, Shimaa, Ferdig, Michael T, Fernández Robledo, José A, Fidock, David A, Florent, Isabelle, Fokou, Patrick VT, Galstian, Ani, Gamo, Francisco Javier, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M, Guha, Rajarshi, Guiguemde, W Armand, Gural, Nil, Guy, R Kiplin, Hansen, Michael AE, Hanson, Kirsten K, Hemphill, Andrew, Hooft van Huijsduijnen, Rob, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B, Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A, Jadhav, Ajit, Naranuntarat Jensen, Amornrat, Jensen, Laran T, Jiang, Rays HY, Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P, Kyle, Dennis E, Lafuente, Maria Jose, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M, Li, Fengwu, Little, David, Liu, Liqiong, Llinás, Manuel, Loza, Maria I, Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, and Maes, Louis

Subjects
Humans, Malaria, Antimalarials, Drug Evaluation, Preclinical, Small Molecule Libraries, Drug Discovery, Neglected Diseases, Datasets as Topic, Drug Evaluation, Preclinical, Virology, Microbiology, Immunology, Medical Microbiology
Abstract

A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemistry programs. The data for all of these assays are presented and analyzed to show how outstanding leads for many indications can be selected. These results reveal the immense potential for translating the dispersed expertise in biological assays involving human pathogens into drug discovery starting points, by providing open access to new families of molecules, and emphasize how a small additional investment made to help acquire and distribute compounds, and sharing the data, can catalyze drug discovery for dozens of different indications. Another lesson is that when multiple screens from different groups are run on the same library, results can be integrated quickly to select the most valuable starting points for subsequent medicinal chemistry efforts.

Published
2016

10. Impact of lymph node status in patients with intrahepatic cholangiocarcinoma treated by major hepatectomy: a review of the National Cancer Database

Author

Jutric, Zeljka, Johnston, W Cory, Hoen, Helena M, Newell, Pippa H, Cassera, Maria A, Hammill, Chet W, Wolf, Ronald F, and Hansen, Paul D

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Digestive Diseases, Rare Diseases, Digestive Diseases - (Gallbladder), Adult, Aged, Bile Duct Neoplasms, Cholangiocarcinoma, Databases, Factual, Female, Hepatectomy, Humans, Kaplan-Meier Estimate, Lymph Node Excision, Lymph Nodes, Lymphatic Metastasis, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, Risk Factors, Time Factors, Treatment Outcome, United States, Surgery, Clinical sciences
Abstract

IntroductionRoutine lymphadenectomy in the surgical treatment of intrahepatic cholangiocarcinoma (ICC) is not routinely performed. We aim to define predictive indicators of survival in patients with positive lymph nodes.MethodsThe National Cancer Data Base (NCDB) was queried for patients who underwent major hepatectomy for ICC between 1998 and 2011. Clinical and pathologic data were assessed using uni- and multi-variate analyses. A sub-analysis was performed on the 160 patients with positive lymph nodes.ResultsOf 849 patients with lymph node data, 57% had at least one lymph node examined. Median survival for lymph node negative patients was 37 months versus 15 months for lymph node positive patients. In lymph node positive patients, poorer survival was associated with not receiving chemotherapy (HR 1.83, p = 0.003), tumor size > 5 cm (p = 0.029), and older age (p < 0.0001). Lymph node positive patients age less than 45 had a median survival of 27 months.ConclusionsOverall survival in patients with lymph node metastases from ICC is poor. Adjuvant therapy was associated with a longer survival in lymph node positive patients, although prospective data are needed. Routine lymphadenectomy should be strongly considered to provide prognostic information and guidance for adjuvant therapy.

Published
2016

11. Correction to: Antimalarial Natural Products

Author

Kingston, David G. I., Cassera, Maria Belen, Kinghorn, A. Douglas, Series Editor, Falk, Heinz, Series Editor, Gibbons, Simon, Series Editor, Asakawa, Yoshinori, Series Editor, Liu, Ji-Kai, Series Editor, Dirsch, Verena M., Series Editor, Appendino, Giovanni, Advisory Editor, Berlinck, Roberto G. S., Advisory Editor, Kobayashi, Jun'ichi, Advisory Editor, Ludwiczuk, Agnieszka, Advisory Editor, Naman, C. Benjamin, Advisory Editor, Mata, Rachel, Advisory Editor, Oberlies, Nicholas H., Advisory Editor, Tasdemir, Deniz, Advisory Editor, Trauner, Dirk, Advisory Editor, Viljoen, Alvaro, Advisory Editor, and Ye, Yang, Advisory Editor

Published
2022
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12. Aptamer-Based Imaging of Polyisoprenoids in the Malaria Parasite.

Author

Zimbres, Flavia M., Merino, Emilio F., Butschek, Grant J., Butler, Joshua H., Ducongé, Frédéric, and Cassera, Maria B.

Subjects
ENDOPLASMIC reticulum, APTAMERS, ALDEHYDES, BIOSYNTHESIS, FATTY acids, PLASMODIUM, GLYCANS
Abstract

Dolichols are isoprenoid end-products of the mevalonate and 2C-methyl-D-erythritol-4-phosphate pathways. The synthesis of dolichols is initiated with the addition of several molecules of isopentenyl diphosphate to farnesyl diphosphate. This reaction is catalyzed by a cis-prenyltransferase and leads to the formation of polyprenyl diphosphate. Subsequent steps involve the dephosphorylation and reduction of the α-isoprene unit by a polyprenol reductase, resulting in the generation of dolichol. The size of the dolichol varies, depending on the number of isoprene units incorporated. In eukaryotes, dolichols are synthesized as a mixture of four or more different lengths. Their biosynthesis is predicted to occur in the endoplasmic reticulum, where dolichols play an essential role in protein glycosylation. In this study, we have developed a selection of aptamers targeting dolichols and enhanced their specificity by incorporating fatty acids for negative selection. One aptamer showed high enrichment and specificity for linear polyisoprenoids containing at least one oxygen atom, such as an alcohol or aldehyde, in the α-isoprene unit. The selected aptamer proved to be a valuable tool for the subcellular localization of polyisoprenoids in the malaria parasite. To the best of our knowledge, this is the first time that polyisoprenoids have been localized within a cell using aptamer-based imaging techniques. [ABSTRACT FROM AUTHOR]

Published
2024
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22. In Vitro Diagnostic Assay to Detect SARS-CoV-2-Neutralizing Antibody in Patient Sera Using Engineered ACE-2 Mini-Protein

Author

Pereira de Jesus, Bruna Andersen, primary, Gomes, Anderson Albino, additional, Clark, Alex E., additional, Rodrigues, Tayse Andrade, additional, Ledgerwood-Lee, Melissa, additional, Van Zant, Westley, additional, Brickner, Howard, additional, Wang, Meiqiao, additional, Blum, David L., additional, Cassera, Maria B., additional, Carlin, Aaron F., additional, Aronoff-Spencer, Eliah S., additional, da Silva, Gustavo Felippe, additional, Magalhães, Maria de Lourdes Borba, additional, and Ray, Partha, additional

Published
2022
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31. Two Terpenoid Derivatives with Different 3/5/6/6/5‐Fused Pentacyclic Skeletons from Hedyosmum orientale.

Author

Fan, Yao‐Yue, Zheng, Cheng‐Yu, Zhou, Bin, Zimbres, Flavia M., Cassera, Maria B., and Yue, Jian‐Min

Subjects
NATURAL products, X-ray diffraction, DATA analysis, PEROXIDES
Abstract

Comprehensive Summary: Chemical investigation of Hedyosmum orientale led to the identification of two terpenoid derivatives, dyosmunoids A and B (1 and 2) featuring two different 3/5/6/6/5‐fused pentacyclic ring systems, respectively. Compound 1 is the second natural product of this C25 terpenoid compound class, and compound 2 is a rare dinor‐C25 terpenoid with a peroxide bridge. Their structural elucidation was achieved by the comprehensive analysis of spectroscopic data, single‐crystal X‐ray diffraction, and ECD calculation. Putative biosynthetic pathways for compounds 1 and 2 are proposed. Compound 2 exhibited strong antimalarial activity with an IC50 value of 0.42 μmol·L–1. [ABSTRACT FROM AUTHOR]

Published
2023
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39. Malaria Box-Inspired Discovery of N-Aminoalkyl-β-carboline-3-carboxamides, a Novel Orally Active Class of Antimalarials

Author

Mathew, Jopaul, primary, Ding, Sha, additional, Kunz, Kevin A., additional, Stacy, Emily E., additional, Butler, Joshua H., additional, Haney, Reagan S., additional, Merino, Emilio F., additional, Butschek, Grant J., additional, Rizopoulos, Zaira, additional, Totrov, Maxim, additional, Cassera, Maria B., additional, and Carlier, Paul R., additional

Published
2022
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49. Alkyne modified purines for assessing activation of Plasmodium vivax hypnozoites and growth of pre-erythrocytic and erythrocytic stages in Plasmodium spp.

Author

Botnar, Alona, primary, Lawrence, Grant, additional, Maher, Steven P., additional, Vantaux, Amèlie, additional, Witkowski, Benoît, additional, Shiau, Justine C, additional, Merino, Emilio F, additional, De Vore, David, additional, Yang, Christian, additional, Murray, Cameron, additional, Cassera, Maria Belen, additional, Leahy, James W, additional, and Kyle, Dennis E, additional

Published
2021
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