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Pharmaceuticals
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Targeting Lectins as a Strategy for Developing New Drugs
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Targeting Lectins as a Strategy for Developing New Drugs

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 11745

Special Issue Editors

Dr. Teresa García-Gasca

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Guest Editor
Biomedical research and functional foods. Faculty of Natural Sciences, Autonomous University of Querétaro, Av. de las Ciencias S/N, Juriquilla 76320, Querétaro, Mexico
Interests: lectins with anticancer potential, toxicological and pharmacological studies; food chemistry; food tech-nology; nutraceuticals; phytochemicals with bioactive potential; secondary metabolites; antioxidants; phenols; plant biotechnology; elicitation; nutrition; HPLC techniques; changes in the content of metabo-lites; the role of polyphenols in health
Special Issues, Collections and Topics in MDPI journals
Dr. Ulisses Moreno-Celis

E-Mail Website
Guest Editor
Cell and Molecular Biology Laboratory, Natural Sciences Faculty, Autonomous University of Queretaro, Queretaro 76230, Mexico
Interests: nutrigenetics; polymorphism; chronic non-communicable diseases; biomedicine; biotechnology

Special Issue Information

Dear Colleagues,

Lectins are proteins or glycoproteins that are ubiquitous in all living beings. They take their name from the Latin legere (to select or choose), given their characteristics of selectively recognizing and reversibly binding free or membrane cell carbohydrates, which allows them to identify between different cell types and between normal and cancer cells. They are useful molecules for structural and functional studies of carbohydrates, the identification of physiological or pathological changes in the cell surface and the generation of biological responses involved with cell survival. Therefore, lectins are important tools for the fields of immunology, biochemistry, cell biology, pharmacology and medicine, and have potential uses as diagnostic tools or therapeutic agents. The study of endogenous lectins as therapeutic targets or exogenous lectins as bioactive agents contributes to the discovery and development of new drugs against diseases such as cancer. Because of the biological properties of lectins, the objective of this Special Issue is to highlight important scientific contributions in the field of study of lectins of any origin as part of pharmacological research for drug development.

Dr. Teresa García-Gasca
Dr. Ulisses Moreno-Celis
Guest Editors

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Keywords

  • lectins
  • drug development
  • cancer research
  • immunology
  • biomedicine
  • pharmacology
  • cell signaling

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Published Papers (4 papers)

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Research

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22 pages, 42292 KiB  
Article
EGFR and p38MAPK Contribute to the Apoptotic Effect of the Recombinant Lectin from Tepary Bean (Phaseolus acutifolius) in Colon Cancer Cells
by José Luis Dena-Beltrán, Porfirio Nava-Domínguez, Dulce Palmerín-Carreño, Dania Martínez-Alarcón, Ulisses Moreno-Celis, Magali Valle-Pacheco, José Luis Castro-Guillén, Alejandro Blanco-Labra and Teresa García-Gasca
Pharmaceuticals 2023, 16(2), 290; https://doi.org/10.3390/ph16020290 - 14 Feb 2023
Viewed by 2160
Abstract
Previous works showed that a Tepary bean lectin fraction (TBLF) induced apoptosis on colon cancer cells and inhibited early colonic tumorigenesis. One Tepary bean (TB) lectin was expressed in Pichia pastoris (rTBL-1), exhibiting similarities to one native lectin, where its molecular structure and [...] Read more.
Previous works showed that a Tepary bean lectin fraction (TBLF) induced apoptosis on colon cancer cells and inhibited early colonic tumorigenesis. One Tepary bean (TB) lectin was expressed in Pichia pastoris (rTBL-1), exhibiting similarities to one native lectin, where its molecular structure and in silico recognition of cancer-type N-glycoconjugates were confirmed. This work aimed to determine whether rTBL-1 retained its bioactive properties and if its apoptotic effect was related to EGFR pathways by studying its cytotoxic effect on colon cancer cells. Similar apoptotic effects of rTBL-1 with respect to TBLF were observed for cleaved PARP-1 and caspase 3, and cell cycle G0/G1 arrest and decreased S phase were observed for both treatments. Apoptosis induction on SW-480 cells was confirmed by testing HA2X, p53 phosphorylation, nuclear fragmentation, and apoptotic bodies. rTBL-1 increased EGFR phosphorylation but also its degradation by the lysosomal route. Phospho-p38 increased in a concentration- and time-dependent manner, matching apoptotic markers, and STAT1 showed activation after rTBL-1 treatment. The results show that part of the rTBL-1 mechanism of action is related to p38 MAPK signaling. Future work will focus further on the target molecules of this recombinant lectin against colon cancer. Full article
(This article belongs to the Special Issue Targeting Lectins as a Strategy for Developing New Drugs)
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15 pages, 41347 KiB  
Article
Schinus terebinthifolius Leaf Lectin (SteLL) Reduces the Bacterial and Inflammatory Burden of Wounds Infected by Staphylococcus aureus Promoting Skin Repair
by Marcio Anderson Sousa Nunes, Lucas dos Santos Silva, Deivid Martins Santos, Brenda da Silva Cutrim, Silvamara Leite Vieira, Izadora Souza Soeiro Silva, Simeone Júlio dos Santos Castelo Branco, Mayara de Santana do Nascimento, André Alvares Marques Vale, Ana Paula Silva dos Santos-Azevedo, Adrielle Zagmignan, Joicy Cortez de Sá Sousa, Thiago Henrique Napoleão, Patrícia Maria Guedes Paiva, Valério Monteiro-Neto and Luís Cláudio Nascimento da Silva
Pharmaceuticals 2022, 15(11), 1441; https://doi.org/10.3390/ph15111441 - 21 Nov 2022
Cited by 2 | Viewed by 4685
Abstract
Staphylococcus aureus is commonly found in wound infections where this pathogen impairs skin repair. The lectin isolated from leaves of Schinus terebinthifolius (named SteLL) has antimicrobial and antivirulence action against S. aureus. This study evaluated the effects of topical administration of SteLL on [...] Read more.
Staphylococcus aureus is commonly found in wound infections where this pathogen impairs skin repair. The lectin isolated from leaves of Schinus terebinthifolius (named SteLL) has antimicrobial and antivirulence action against S. aureus. This study evaluated the effects of topical administration of SteLL on mice wounds infected by S. aureus. Seventy-two C57/BL6 mice (6–8 weeks old) were allocated into four groups: (i) uninfected wounds; (ii) infected wounds, (iii) infected wounds treated with 32 µg/mL SteLL solution; (iv) infected wounds treated with 64 µg/mL SteLL solution. The excisional wounds (64 mm2) were induced on the dorsum and infected by S. aureus 432170 (4.0 × 106 CFU/wound). The daily treatment started 1-day post-infection (dpi). The topical application of both SteLL concentrations significantly accelerated the healing of S. aureus-infected wounds until the 7th dpi, when compared to untreated infected lesions (reductions of 1.95–4.55-fold and 1.79–2.90-fold for SteLL at 32 µg/mL and 64 µg/mL, respectively). The SteLL-based treatment also amended the severity of wound infection and reduced the bacterial load (12-fold to 72-fold for 32 µg/mL, and 14-fold to 282-fold for 64 µg/mL). SteLL-treated wounds show higher collagen deposition and restoration of skin structure than other groups. The bacterial load and the levels of inflammatory markers (IL-6, MCP-1, TNF-α, and VEGF) were also reduced by both SteLL concentrations. These results corroborate the reported anti-infective properties of SteLL, making this lectin a lead candidate for developing alternative agents for the treatment of S. aureus-infected skin lesions. Full article
(This article belongs to the Special Issue Targeting Lectins as a Strategy for Developing New Drugs)
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11 pages, 3251 KiB  
Article
The Anxiolytic Activity of Schinus terebinthifolia Leaf Lectin (SteLL) Is Dependent on Monoaminergic Signaling although Independent of the Carbohydrate-Binding Domain of the Lectin
by Bárbara Raíssa Ferreira de Lima, Leydianne Leite de Siqueira Patriota, Amanda de Oliveira Marinho, Jainaldo Alves da Costa, Thiago Henrique Napoleão, Michelle Melgarejo da Rosa and Patrícia Maria Guedes Paiva
Pharmaceuticals 2022, 15(11), 1364; https://doi.org/10.3390/ph15111364 - 7 Nov 2022
Cited by 9 | Viewed by 1937
Abstract
The potential of plant lectins (carbohydrate-binding proteins) for the treatment of neurological disorders such as anxiety and depression has started to be reported in the last few years. Schinus terebinthifolia leaves contain a lectin called SteLL, which has displayed antimicrobial, immunomodulatory, antitumor, and [...] Read more.
The potential of plant lectins (carbohydrate-binding proteins) for the treatment of neurological disorders such as anxiety and depression has started to be reported in the last few years. Schinus terebinthifolia leaves contain a lectin called SteLL, which has displayed antimicrobial, immunomodulatory, antitumor, and analgesic activities. However, the effects of SteLL on the Central Nervous System (CNS) have not yet been determined. In this study, we investigated the in vivo anxiolytic effect of SteLL in mice using the open field (OF) and elevated plus maze (EPM) tests. In the OF, SteLL (1, 2, and 4 mg/kg, i.p.) did not interfere with the number of crossings but significantly reduced the number of rearings. In the EPM, SteLL 4 mg/kg and the combination SteLL (1 mg/kg) plus diazepam (1 mg/kg) significantly increased the time spent in the open arms while reducing the time spent in the closed arms. The anxiolytic effect of SteLL did not seem to be dependent on the carbohydrate-binding domain of the lectin. Nevertheless, the SteLL effect in the EPM was reversed by the pretreatment with the pharmacological antagonists of the α2-adrenoceptor, 5-HT2A/2C serotonin receptor, and the D1 dopamine receptor. Overall, our results suggest that the anxiolytic effect of SteLL is dependent on the monoaminergic signaling cascade. Full article
(This article belongs to the Special Issue Targeting Lectins as a Strategy for Developing New Drugs)
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Review

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13 pages, 1253 KiB  
Review
Role of Galectin in Cardiovascular Conditions including Cirrhotic Cardiomyopathy
by Hongqun Liu, Sang-Youn Hwang and Samuel S. Lee
Pharmaceuticals 2023, 16(7), 978; https://doi.org/10.3390/ph16070978 - 7 Jul 2023
Cited by 4 | Viewed by 1850
Abstract
Abnormal cardiac function in the setting of cirrhosis and in the absence of a primary cardiac disease is known as cirrhotic cardiomyopathy. The pathogenesis of cirrhotic cardiomyopathy is multifactorial but broadly is comprised of two pathways. The first is due to cirrhosis and [...] Read more.
Abnormal cardiac function in the setting of cirrhosis and in the absence of a primary cardiac disease is known as cirrhotic cardiomyopathy. The pathogenesis of cirrhotic cardiomyopathy is multifactorial but broadly is comprised of two pathways. The first is due to cirrhosis and synthetic liver failure with abnormal structure and function of many substances, including proteins, lipids, hormones, and carbohydrates such as lectins. The second is due to portal hypertension which invariably accompanies cirrhosis. Portal hypertension leads to a leaky, congested gut with resultant endotoxemia and systemic inflammation. This inflammatory phenotype comprises oxidative stress, cellular apoptosis, and inflammatory cell infiltration. Galectins exert all these pro-inflammatory mechanisms across many different tissues and organs, including the heart. Effective therapies for improving cardiac function in patients with cirrhosis are not available. Conventional strategies for other noncirrhotic heart diseases, including vasodilators, are not feasible because of the significant baseline vasodilation in cirrhotic patients. Therefore, exploring new treatment modalities for cirrhotic cardiomyopathy is of great importance. Galectin-3 inhibitors such as modified citrus pectin, N-acetyllactosamine, TD139 and GB0139 exert anti-apoptotic, anti-oxidative and anti-inflammatory effects and thus have potential therapeutic interest. This review briefly summarizes the physiological and pathophysiological role of galectin and specifically examines its role in cardiac disease processes. We present a more detailed discussion of galectin in cardiovascular complications of cirrhosis, particularly cirrhotic cardiomyopathy. Finally, therapeutic studies of galectin-3 inhibitors in cirrhotic cardiomyopathy are reviewed. Full article
(This article belongs to the Special Issue Targeting Lectins as a Strategy for Developing New Drugs)
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