Article
Biochemistry & Molecular Biology
Andreina Henriquez-Figuereo, Mercedes Alcon, Esther Moreno, Carmen Sanmartin, Socorro Espuelas, Hector de Lucio, Antonio Jimenez-Ruiz, Daniel Plano
Summary: Leishmaniasis is a disease that is currently treated with outdated drugs that have many limitations. Recent studies have shown that selenium compounds could be a promising option for innovative therapy. In this study, a new library of 20 selenocyanate and diselenide derivatives were designed based on the structure of an existing leishmanicidal drug. These compounds showed high efficacy and low cytotoxicity in screening tests and exhibited potent activity against the parasite. Furthermore, they also activated the immune response in macrophages. Overall, these compounds have the potential to be developed as new drugs for leishmaniasis treatment.
BIOORGANIC CHEMISTRY
(2023)
Article
Microbiology
Mikel Etxebeste-Mitxeltorena, Daniel Plano, Socorro Espuelas, Esther Moreno, Carlos Aydillo, Antonio Jimenez-Ruiz, Juan Carlos Garcia Soriano, Carmen Sanmartin
Summary: This study synthesized and characterized 13 new selenophosphoramidate derivatives, with compound 1g showing more effectiveness than the reference compounds. Theoretical calculations indicated that compound 1g possessed properties suitable for orally available drugs. The selenophosphoramidate functionalities could potentially serve as a scaffold for developing new agents for leishmania treatment.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Parasitology
Minelly A. da Silva, Harold H. Fokoue, Saara N. Fialho, Ana Paula de A. dos Santos, Norton R. D. L. P. Rossi, Aurileya de J. Gouveia, Amalia S. Ferreira, Guilherme M. Passarini, Ana F. G. Garay, Jorge J. Alfonso, Andreimar M. Soares, Fernando B. Zanchi, Massuo J. Kato, Carolina B. G. Teles, Christian C. Kuehn
Summary: Leishmaniasis is considered a neglected disease, leading to a lack of financial motivation for research efforts in finding biologically active substances. This study identified compounds with promising leishmanicidal activity, such as piplartine, and investigated their possible mechanisms of action.
PARASITOLOGY RESEARCH
(2021)
Article
Chemistry, Medicinal
Theo Battista, Stefano Federico, Simone Brogi, Luca Pozzetti, Tuhina Khan, Stefania Butini, Anna Ramunno, Eleonora Fiorentino, Stefania Orsini, Trentina Di Muccio, Annarita Fiorillo, Cecile Exertier, Daniel Di Risola, Andrea Ilari, Giuseppe Campiani, Gianni Colotti, Sandra Gemma
Summary: Leishmania spp. is a significant public health issue, and developing better therapeutic drugs is urgently needed. This study optimized a novel class of Leishmania inhibitors through various approaches and identified potent and selective compounds that could be used for treating leishmaniasis and related diseases.
ACS INFECTIOUS DISEASES
(2022)
Article
Chemistry, Multidisciplinary
Andres Sanchez Alberti, Maria F. Beer, Natacha Cerny, Augusto E. Bivona, Lucas Fabian, Celina Morales, Albertina Moglioni, Emilio L. Malchiodi, Osvaldo J. Donadel, Valeria P. Sulsen
Summary: The study demonstrated that cumanin diacetate showed promising activity and selectivity against Trypanosoma cruzi, especially in inhibiting parasite replication in amastigote forms. This compound could be a potential candidate for further studies in the development of new therapies against Chagas disease.
Article
Biochemistry & Molecular Biology
Emanuel Paula Magalhaes, Naiara Dutra Barroso Gomes, Tiago Araujo De Freitas, Brenna Pinheiro Silva, Lyanna Rodrigues Ribeiro, Francisco Wagner Queiroz Ameida-Neto, Marcia Machado Marinho, Pedro De Lima-Neto, Emmanuel Silva Marinho, Helcio Silva dos Santos, Alexandre Magno Rodrigues Teixeira, Tiago Lima Sampaio, Ramon Roseo Paula Pessoa Bezerra De Menezes, Alice Maria Costa Martins
Summary: This study evaluated the effect of novel chalcones on Trypanosoma cruzi and host cells. Chlorine substitution reduced the toxicity on host cells without compromising the effect on the parasite. The mechanism of action involves membrane damage, oxidative stress, and possible enzyme interactions.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Chemistry, Medicinal
Fardous F. El-Senduny, Sameh M. Shabana, Daniel Rosel, Jan Brabek, Ismail Althagafi, Gregor Angeloni, Georg Manolikakes, Saad Shaaban
Summary: The study demonstrated the promising anticancer properties of 1,1'-(Diselanediylbis(4,1-phenylene))bis(3-phenylurea) (14) against HepG2 cells, with no toxicity to normal human skin fibroblasts. The urea-functionalized organoselenium compound showed efficient anti-HepG2 activity at sub-micromolar concentrations.
FUTURE MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Sohaila Andleeb, Imtiaz-ud-Din, Muhammad Khawar Rauf, Syed Sikander Azam, Ihsan-ul Haq, Muhammad Nawaz Tahir, Naila Zaman
Summary: A series of heteroleptic triorganobismuth(V) biscarboxylates were synthesized, characterized, and evaluated for their biological potential against L. tropica. The synthesized complexes exhibited moderate to significant activity against leishmania parasites.
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Calebe H. L. Silva, Jessica Soares, Carlos R. M. Peixoto, Juliano B. Azeredo, Bruno S. de Souza, Juliano A. Rohers, Marcelo Godoi
Summary: A straightforward method for the synthesis of symmetrical thiosulfonates through direct oxidative coupling of thiols using dibutyl diselenide as a catalyst has been reported. The target products were obtained in good yields, and mechanistic studies suggested a radical reaction pathway.
Editorial Material
Chemistry, Medicinal
Kaio M. Santiago-Silva, Priscila G. Camargo, Marcelle L. F. Bispo
Summary: Leishmaniasis is a global neglected tropical disease caused by parasitic protozoa. The existing treatment options are limited and have various drawbacks, leading to treatment challenges and the emergence of drug-resistant strains. Therefore, the development of new therapies for leishmaniasis is necessary. This review focuses on inhibiting essential targets involved in parasite growth, survival, and infectivity, such as Arginase and trypanothione synthase, and discusses recent discoveries of promising enzyme inhibitors.
MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Anurag Kumar, Prajakta Nimsarkar, Shailza Singh
Summary: Systems pharmacology is useful for understanding the complex relationships between biological systems, drugs, and infection models. In this study, benzimidazole derivatives were designed as inhibitors for TryR from Leishmania major using computational and experimental approaches. In vitro and in vivo experiments showed that compound C1 has significant anti-parasitic activity.
Article
Pharmacology & Pharmacy
Christian Espinosa-Bustos, Mariana Ortiz Perez, Alonzo Gonzalez-Gonzalez, Ana Maria Zarate, Gildardo Rivera, Javier A. Belmont-Diaz, Emma Saavedra, Mauricio A. Cuellar, Karina Vazquez, Cristian O. Salas
Summary: In this study, a series of new amino naphthoquinone derivatives were synthesized and evaluated for their activity against Trypanosoma cruzi strains. Compounds 2e and 7j showed the lowest IC50 values and 7j exhibited higher activity and selectivity than the reference drug benznidazole. Molecular docking studies revealed that 7j had a good interaction profile on T. cruzi trypanothione reductase (TcTR) and it was predicted to have a favorable pharmacokinetic profile for oral administration.
Article
Immunology
Job D. F. Inacio, Myslene S. Fonseca, Gabriel Limaverde-Sousa, Ana M. Tomas, Helena Castro, Elmo E. Almeida-Amaral
Summary: EGCG kills Leishmania infantum promastigotes by disrupting their intracellular redox balance through mechanisms including mitochondrial depolarization, decreased intracellular ATP levels, increased intracellular H2O2 levels, and potentially acting as a competitive inhibitor of the enzyme trypanothione reductase.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Claudia Lopez-Lira, Ricardo A. Tapia, Alejandra Herrera, Michel Lapier, Juan D. Maya, Jorge Soto-Delgado, Allen G. Oliver, A. Graham Lappin, Eugenio Uriarte
Summary: The design and synthesis of new 2-phenyl(pyridinyl)benzimidazolequinones and their 5-phenoxy derivatives demonstrate potent anti-Trypanosoma cruzi activity. Compound 11a shows significantly higher activity compared to nifurtimox. Molecular docking studies suggest that these compounds could have a multitarget profile.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
A. Zabala-Penafiel, G. Dias-Lopes, F. Souza-Silva, L. F. C. Miranda, F. Conceicao-Silva, C. R. Alves
Summary: Leishmania parasites have a defense mechanism called the trypanothione system, which plays a central role in processing pentavalent antimony and is related to resistance. The study assessed the effect of trivalent and pentavalent antimony on Trypanothione Reductase activity in two clinical isolates of Leishmania (Viannia) braziliensis. The results showed differences in susceptibility profiles and trypanothione reductase activity between the isolates.
Article
Endocrinology & Metabolism
Deepkamal N. Karelia, Sangyub Kim, Daniel Plano, Arun K. Sharma, Cheng Jiang, Junxuan Lu
Summary: AS-10, a novel selenium-aspirin compound, exhibits potent cytotoxicity against prostate cancer cells through promoting histone acetylation and inducing cell cycle arrest and apoptosis.
Article
Chemistry, Medicinal
Andreina Henriquez-Figuereo, Cristina Moran-Serradilla, Eduardo Angulo-Elizari, Carmen Sanmartin, Daniel Plano
Summary: Neglected tropical diseases (NTDs) are a group of infectious diseases caused by protozoa, with a high incidence and prevalence in developing countries. Economic factors hinder the management of these diseases, and there is a lack of effective drugs and high costs. This study aims to identify novel chalcogen-derived molecules against Chagas disease, leishmaniasis, and human African trypanosomiasis (HAT).
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Nora Astrain-Redin, Irene Talavera, Esther Moreno, Maria J. Ramirez, Nuria Martinez-Saez, Ignacio Encio, Arun K. Sharma, Carmen Sanmartin, Daniel Plano
Summary: Nowadays, Se-containing molecules, such as ebselen, have demonstrated well-established preventive effects against cancer and Alzheimer's disease. In this study, a total of 39 Se-derivatives were synthesized and tested for their antioxidant and antiproliferative activities. Compound 13a showed concentration- and time-dependent radical scavenging activity, while compounds 14a and 17a exhibited high activity in certain cancer cell lines. Compound 14a also showed promising potential as an anti-Alzheimer agent.
Article
Biochemistry & Molecular Biology
Nora Astrain-Redin, Niccolo Paoletti, Daniel Plano, Alessandro Bonardi, Paola Gratteri, Andrea Angeli, Carmen Sanmartin, Claudiu T. Supuran
Summary: In the search for new cancer treatments, organoselenium compounds and carbonic anhydrase inhibitors have shown promise. Selenium-containing compounds, especially selenols, have demonstrated potent inhibition of tumor-associated CA isoforms. In this study, selenoesters combining NSAIDs and natural product fragments were evaluated as nonclassical inhibitors of tumor-associated CA isoforms.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Nora Astrain-Redin, Carmen Sanmartin, Arun K. Sharma, Daniel Plano
Summary: Since ancient times, natural products have been a rich source of bioactive molecules for cancer treatment. Many allyl derivatives found in garlic, cinnamon, nutmeg, or mustard have shown anticancer activity in various cancers. Synthetic products with allyl fragments, such as 17-AAG, have also demonstrated potent anticancer properties in clinical trials. This Perspective compiles recent advances in natural and synthetic allyl derivatives, which have the potential to become future cancer drug candidates.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Andreina Henriquez-Figuereo, Mercedes Alcon, Esther Moreno, Carmen Sanmartin, Socorro Espuelas, Hector de Lucio, Antonio Jimenez-Ruiz, Daniel Plano
Summary: Leishmaniasis is a disease that is currently treated with outdated drugs that have many limitations. Recent studies have shown that selenium compounds could be a promising option for innovative therapy. In this study, a new library of 20 selenocyanate and diselenide derivatives were designed based on the structure of an existing leishmanicidal drug. These compounds showed high efficacy and low cytotoxicity in screening tests and exhibited potent activity against the parasite. Furthermore, they also activated the immune response in macrophages. Overall, these compounds have the potential to be developed as new drugs for leishmaniasis treatment.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Andreina Henriquez-Figuereo, Esther Moreno, Carmen Sanmartin, Daniel Plano
Summary: This work focuses on the design, synthesis, and biological activities of new selenoester derivatives and thioester homologs with potential as therapeutic candidates for leishmaniasis. These compounds showed structural similarities to antileishmanial drugs and exhibited high sensitivity against Leishmania infantum, the causative agent of visceral leishmaniasis. Four selanylacetic acid derivatives demonstrated significant leishmanicidal characteristics and pharmacological synergism with the oral drug miltefosine.
Article
Biochemistry & Molecular Biology
Nora Astrain-Redin, Asif Raza, Ignacio Encio, Arun K. Sharma, Daniel Plano, Carmen Sanmartin
Summary: Oxidative stress provides cancer cells with advantages for disease progression. Se-containing molecules with anticancer and antioxidant activity were synthesized and showed potent radical scavenging and anticancer activity. New Se derivatives resembling natural products exhibited high radical scavenging activity and antiproliferative effects.
Article
Biochemistry & Molecular Biology
Sandra Ramos-Inza, Cesar Aliaga, Ignacio Encio, Asif Raza, Arun K. Sharma, Carlos Aydillo, Nuria Martinez-Saez, Carmen Sanmartin, Daniel Plano
Summary: This study reports a novel Se-NSAID derivative that exhibits antioxidant and anticancer activity by introducing Se into organic molecules. In vitro experiments showed that one of the derivatives not only displayed the strongest antioxidant activity, but also selectively induced toxicity in cancer cells, indicating its potential therapeutic applications. In vivo experiments demonstrated that the derivative significantly suppressed tumor growth without apparent toxicity.
Article
Chemistry, Medicinal
Itziar Galarreta-Rodriguez, Mikel Etxebeste-Mitxeltorena, Esther Moreno, Daniel Plano, Carmen Sanmartin, Saad Megahed, Neus Feliu, Wolfgang J. Parak, Eneko Garaio, Izaskun Gil de Muro, Luis Lezama, Idoia Ruiz de Larramendi, Maite Insausti
Summary: In this study, a drug carrier nanosystem based on Fe3O4 nanoparticles with large heating power was designed. The nanosystem showed high selectivity against colon cancer cells and demonstrated good efficacy as a magnetic hyperthermia inductor.