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  1. Article ; Online: Unmasking the Mechanism behind Miltefosine: Revealing the Disruption of Intracellular Ca

    Benaim, Gustavo / Paniz-Mondolfi, Alberto

    Biomolecules

    2024  Volume 14, Issue 4

    Abstract: Originally developed as a chemotherapeutic agent, miltefosine (hexadecylphosphocholine) is an inhibitor of phosphatidylcholine synthesis with proven antiparasitic effects. It is the only oral drug approved for the treatment of Leishmaniasis and American ... ...

    Abstract Originally developed as a chemotherapeutic agent, miltefosine (hexadecylphosphocholine) is an inhibitor of phosphatidylcholine synthesis with proven antiparasitic effects. It is the only oral drug approved for the treatment of Leishmaniasis and American Trypanosomiasis (Chagas disease). Although its precise mechanisms are not yet fully understood, miltefosine exhibits broad-spectrum anti-parasitic effects primarily by disrupting the intracellular Ca
    MeSH term(s) Humans ; Phosphorylcholine/analogs & derivatives ; Phosphorylcholine/pharmacology ; Phosphorylcholine/therapeutic use ; Chagas Disease/drug therapy ; Chagas Disease/parasitology ; Chagas Disease/metabolism ; Calcium/metabolism ; Leishmaniasis/drug therapy ; Leishmaniasis/metabolism ; Leishmaniasis/parasitology ; Homeostasis/drug effects ; Animals ; Antiprotozoal Agents/pharmacology ; Antiprotozoal Agents/therapeutic use ; Mitochondria/metabolism ; Mitochondria/drug effects ; Leishmania/drug effects ; Leishmania/metabolism ; Trypanosoma cruzi/drug effects ; Trypanosoma cruzi/metabolism
    Chemical Substances miltefosine (53EY29W7EC) ; Phosphorylcholine (107-73-3) ; Calcium (SY7Q814VUP) ; Antiprotozoal Agents
    Language English
    Publishing date 2024-03-27
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom14040406
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Editorial: Chagas disease novel drug targets and treatments.

    Duschak, Vilma G / Paniz Mondolfi, Alberto E / Benaim, Gustavo

    Frontiers in cellular and infection microbiology

    2023  Volume 13, Page(s) 1199715

    Language English
    Publishing date 2023-05-26
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2023.1199715
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Determination of Intracellular Ca

    Rey-Cibati, André / Valladares-Delgado, Mariana / Benaim, Gustavo

    Bio-protocol

    2020  Volume 10, Issue 18, Page(s) e3766

    Abstract: ... ...

    Abstract Ca
    Language English
    Publishing date 2020-09-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2833269-6
    ISSN 2331-8325 ; 2331-8325
    ISSN (online) 2331-8325
    ISSN 2331-8325
    DOI 10.21769/BioProtoc.3766
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Effects of SQ109 on Trichomonas vaginalis.

    de Souza, Tatiana Guinancio / Granado, Renato / Benaim, Gustavo / de Souza, Wanderley / Benchimol, Marlene

    Experimental parasitology

    2023  Volume 250, Page(s) 108549

    Abstract: Trichomonas vaginalis is a protozoan that causes human trichomoniasis, a sexually transmitted infection (STI) that affects approximately 278 million people worldwide. The current treatment for human trichomoniasis is based on 1-(2-hydroxyethyl)-2-methyl- ... ...

    Abstract Trichomonas vaginalis is a protozoan that causes human trichomoniasis, a sexually transmitted infection (STI) that affects approximately 278 million people worldwide. The current treatment for human trichomoniasis is based on 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole, known as Metronidazole (MTZ). Although effective in eliminating parasitic infection, MTZ is related to serious adverse effects and is not recommended during pregnancy. In addition, some strains are resistant to 5'-nitroimidazoles, prompting the development of alternative drugs for trichomoniasis. Here we show that SQ109 [N-adamantan-2-yl-N'-((E)-3,7-dimethyl-octa- 2,6-dienyl)-ethane-1,2-diamine], a drug under development (antitubercular drug candidate that completed Phase IIb/III) for the treatment of tuberculosis, and previously tested in Trypanosoma cruzi and Leishmania. SQ109 inhibited T.vaginalis growth with an IC50 of 3.15 μM. We used scanning and transmission electron microscopy to visualize the ultrastructural alterations induced by SQ109. The microscopy analysis showed morphological changes on the protozoan surface, where the cells became rounded with increasing surface projections. In addition, the hydrogenosomes increased their size and area occupied in the cell. Furthermore, the volume and a significant association of glycogen particles with the organelle were seen to be altered. A bioinformatics search was done about the compound to find its possible targets and mechanisms of action. Our observations identify SQ109 as a promising compound against T. vaginalis in vitro, suggesting its potential utility as an alternative chemotherapy for trichomoniasis.
    MeSH term(s) Female ; Humans ; Trichomonas vaginalis ; Antiprotozoal Agents/pharmacology ; Antiprotozoal Agents/therapeutic use ; Trichomonas Vaginitis/drug therapy ; Metronidazole/pharmacology ; Metronidazole/therapeutic use ; Trichomonas Infections/drug therapy
    Chemical Substances Antiprotozoal Agents ; Metronidazole (140QMO216E) ; N-geranyl-N'-(2-adamantyl)ethane-1,2-diamine
    Language English
    Publishing date 2023-05-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 391089-1
    ISSN 1090-2449 ; 0014-4894
    ISSN (online) 1090-2449
    ISSN 0014-4894
    DOI 10.1016/j.exppara.2023.108549
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Ud II Zs.159: Show issues Location:
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  5. Article ; Online: The Rationale for Use of Amiodarone and its Derivatives for the Treatment of Chagas' Disease and Leishmaniasis.

    Benaim, Gustavo / Paniz-Mondolfi, Alberto E / Sordillo, Emilia Mia

    Current pharmaceutical design

    2020  Volume 27, Issue 15, Page(s) 1825–1833

    Abstract: The repurposing or repositioning of previously-approved drugs has become an accepted strategy for the expansion of the pharmacopeia for neglected diseases. Accordingly, amiodarone, an inexpensive and extensively- used class III antiarrhythmic has been ... ...

    Abstract The repurposing or repositioning of previously-approved drugs has become an accepted strategy for the expansion of the pharmacopeia for neglected diseases. Accordingly, amiodarone, an inexpensive and extensively- used class III antiarrhythmic has been proposed as a treatment for Chagas' disease and leishmaniasis. Amiodarone has a potent trypanocidal and leishmanicidal action, mainly acting through the disruption of parasite intracellular Ca
    MeSH term(s) Amiodarone/pharmacology ; Amiodarone/therapeutic use ; Animals ; Calcium ; Chagas Disease/drug therapy ; Dogs ; Leishmaniasis/drug therapy ; Trypanocidal Agents ; Trypanosoma cruzi
    Chemical Substances Trypanocidal Agents ; Amiodarone (N3RQ532IUT) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2020-09-08
    Publishing country United Arab Emirates
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1304236-1
    ISSN 1873-4286 ; 1381-6128
    ISSN (online) 1873-4286
    ISSN 1381-6128
    DOI 10.2174/1381612826666200928161403
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Effects of amiodarone, amioder, and dronedarone on Trichomonas vaginalis.

    de Souza, Tatiana Guinancio / Benaim, Gustavo / de Souza, Wanderley / Benchimol, Marlene

    Parasitology research

    2022  Volume 121, Issue 6, Page(s) 1761–1773

    Abstract: Trichomonas vaginalis is a protozoan that causes human trichomoniasis, the most common non-viral sexually transmitted infection (STI) affecting approximately 278 million people worldwide. The current treatment for trichomoniasis is based on 1-(2- ... ...

    Abstract Trichomonas vaginalis is a protozoan that causes human trichomoniasis, the most common non-viral sexually transmitted infection (STI) affecting approximately 278 million people worldwide. The current treatment for trichomoniasis is based on 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole, known as metronidazole (MTZ). Although effective in clearing the parasite infection, MTZ is related to provoking severe side effects, and it is not recommended during pregnancy. In addition, some strains present resistance to 5'-nitroimidazoles, making urgent the development of alternative drugs for trichomoniasis. Amiodarone, an antiarrhythmic drug, exerts a significant anti-parasite effect, mainly due to its interference with calcium homeostasis and the biosynthesis of sterols. Therefore, we decided to test the effect of amiodarone and two other related compounds (amioder and dronedarone) on T. vaginalis. Our observations show that amiodarone stimulated, rather than inhibited, parasite growth, induced cell aggregation, and glycogen accumulation. Furthermore, the other two compounds displayed anti-parasite activity with IC50 of 3.15 and 11 µM, respectively, and the apoptosis-like process killed the cells. In addition, cells exhibited morphological changes, including an effect on hydrogenosomes structure.
    MeSH term(s) Amiodarone/pharmacology ; Amiodarone/therapeutic use ; Dronedarone/pharmacology ; Dronedarone/therapeutic use ; Female ; Humans ; Metronidazole/pharmacology ; Metronidazole/therapeutic use ; Trichomonas Infections/parasitology ; Trichomonas Vaginitis/drug therapy ; Trichomonas vaginalis
    Chemical Substances Metronidazole (140QMO216E) ; Dronedarone (JQZ1L091Y2) ; Amiodarone (N3RQ532IUT)
    Language English
    Publishing date 2022-04-18
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 284966-5
    ISSN 1432-1955 ; 0932-0113 ; 0044-3255
    ISSN (online) 1432-1955
    ISSN 0932-0113 ; 0044-3255
    DOI 10.1007/s00436-022-07521-8
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    Uh II Zs.124: Show issues Location:
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  7. Article ; Online: Effects of SQ109 on Trichomonas vaginalis

    de Souza, Tatiana Guinancio / Granado, Renato / Benaim, Gustavo / Souza, Wanderley de / Benchimol, Marlene

    Experimental Parasitology. 2023 July, v. 250 p.108549-

    2023  

    Abstract: Trichomonas vaginalis is a protozoan that causes human trichomoniasis, a sexually transmitted infection (STI) that affects approximately 278 million people worldwide. The current treatment for human trichomoniasis is based on 1-(2-hydroxyethyl)-2-methyl- ... ...

    Abstract Trichomonas vaginalis is a protozoan that causes human trichomoniasis, a sexually transmitted infection (STI) that affects approximately 278 million people worldwide. The current treatment for human trichomoniasis is based on 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole, known as Metronidazole (MTZ). Although effective in eliminating parasitic infection, MTZ is related to serious adverse effects and is not recommended during pregnancy. In addition, some strains are resistant to 5′-nitroimidazoles, prompting the development of alternative drugs for trichomoniasis. Here we show that SQ109 [N-adamantan-2-yl-N'-((E)-3,7-dimethyl-octa- 2,6-dienyl)-ethane-1,2-diamine], a drug under development (antitubercular drug candidate that completed Phase IIb/III) for the treatment of tuberculosis, and previously tested in Trypanosoma cruzi and Leishmania. SQ109 inhibited T.vaginalis growth with an IC50 of 3.15 μM. We used scanning and transmission electron microscopy to visualize the ultrastructural alterations induced by SQ109. The microscopy analysis showed morphological changes on the protozoan surface, where the cells became rounded with increasing surface projections. In addition, the hydrogenosomes increased their size and area occupied in the cell. Furthermore, the volume and a significant association of glycogen particles with the organelle were seen to be altered. A bioinformatics search was done about the compound to find its possible targets and mechanisms of action. Our observations identify SQ109 as a promising compound against T. vaginalis in vitro, suggesting its potential utility as an alternative chemotherapy for trichomoniasis.
    Keywords Leishmania ; Trichomonas vaginalis ; Trypanosoma cruzi ; antibiotics ; bioinformatics ; drug therapy ; glycogen ; humans ; inhibitory concentration 50 ; metronidazole ; parasitology ; pregnancy ; sexually transmitted diseases ; transmission electron microscopy ; trichomoniasis ; tuberculosis ; SQ109 ; Chemotherapy ; Hydrogenosome
    Language English
    Dates of publication 2023-07
    Publishing place Elsevier Inc.
    Document type Article ; Online
    ZDB-ID 391089-1
    ISSN 1090-2449 ; 0014-4894
    ISSN (online) 1090-2449
    ISSN 0014-4894
    DOI 10.1016/j.exppara.2023.108549
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: Editorial: Advances in the Molecular Biology of Trypanosomatid Pathogens: New Strategies Against Ancient Enemies.

    Benaim, Gustavo / Paniz-Mondolfi, Alberto E / Ramírez, Juan David / Sordillo, Emilia Mia

    Frontiers in cellular and infection microbiology

    2021  Volume 11, Page(s) 777008

    MeSH term(s) Chagas Disease ; Humans ; Leishmaniasis ; Molecular Biology ; Trypanosoma cruzi
    Language English
    Publishing date 2021-10-06
    Publishing country Switzerland
    Document type Editorial ; Research Support, Non-U.S. Gov't
    ZDB-ID 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2021.777008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Phosphorylation-induced conformational changes of photoactivated rhodopsin probed by fluorescent labeling at Cys

    Rodríguez, Sheerly / Silva, May-Li / Benaím, Gustavo / Bubis, José

    Biochimie

    2018  Volume 150, Page(s) 57–69

    Abstract: In order to monitor conformational changes following photoactivation and phosphorylation of bovine rhodopsin, the two reactive sulfhydryl groups at ... ...

    Abstract In order to monitor conformational changes following photoactivation and phosphorylation of bovine rhodopsin, the two reactive sulfhydryl groups at Cys
    MeSH term(s) Animals ; Biofilms ; Bridged Bicyclo Compounds/chemistry ; Bridged Bicyclo Compounds/metabolism ; Cattle ; Cysteine/chemistry ; Cysteine/metabolism ; Fluorescence ; Molecular Conformation ; Phosphorylation/physiology ; Protein Conformation ; Rhodopsin/chemistry ; Rhodopsin/metabolism
    Chemical Substances Bridged Bicyclo Compounds ; Rhodopsin (9009-81-8) ; Cysteine (K848JZ4886) ; monobromobimane (V23UK0CYXL)
    Language English
    Publishing date 2018-05-04
    Publishing country France
    Document type Journal Article
    ZDB-ID 120345-9
    ISSN 1638-6183 ; 0300-9084
    ISSN (online) 1638-6183
    ISSN 0300-9084
    DOI 10.1016/j.biochi.2018.04.025
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uc I Zs.135: Show issues Location:
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  10. Article ; Online: Structural Analysis and Diversity of Calmodulin-Binding Domains in Membrane and Intracellular Ca

    Mantilla, Génesis / Peréz-Gordones, María C / Cisneros-Montufar, Soledad / Benaim, Gustavo / Navarro, Juan-Carlos / Mendoza, Marta / Ramírez-Iglesias, José R

    The Journal of membrane biology

    2022  Volume 256, Issue 2, Page(s) 159–174

    Abstract: The plasma membrane and autoinhibited ... ...

    Abstract The plasma membrane and autoinhibited Ca
    MeSH term(s) Animals ; Calmodulin/genetics ; Calmodulin/chemistry ; Calmodulin/metabolism ; Adenosine Triphosphatases/metabolism ; Phylogeny ; Cell Membrane/metabolism ; Amino Acids/metabolism
    Chemical Substances Calmodulin ; Adenosine Triphosphatases (EC 3.6.1.-) ; Amino Acids
    Language English
    Publishing date 2022-12-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3082-x
    ISSN 1432-1424 ; 0022-2631
    ISSN (online) 1432-1424
    ISSN 0022-2631
    DOI 10.1007/s00232-022-00275-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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