Next Article in Journal
Quantification of Caffeine and Chlorogenic Acid in Green and Roasted Coffee Samples Using HPLC-DAD and Evaluation of the Effect of Degree of Roasting on Their Levels
Previous Article in Journal
Computational Approaches: Drug Discovery and Design in Medicinal Chemistry and Bioinformatics
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Molecules
Volume 26
Issue 24
10.3390/molecules26247501
molecules-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Synthesis of sp2-Iminosugar Selenoglycolipids as Multitarget Drug Candidates with Antiproliferative, Leishmanicidal and Anti-Inflammatory Properties

by
Elena M. Sánchez-Fernández
1,*,
Raquel García-Hernández
2,
Francisco Gamarro
2,
Ana I. Arroba
3,
Manuel Aguilar-Diosdado
3,
José M. Padrón
4,
José M. García Fernández
5 and
Carmen Ortiz Mellet
1
1
Department of Organic Chemistry, Faculty of Chemistry, University of Seville, C/Profesor García González 1, 41012 Seville, Spain
2
Instituto de Parasitología y Biomedicina “López-Neyra”, Parque Tecnológico de Ciencias de la Salud, 18016 Granada, Spain
3
Research Unit, Biomedical Research and Innovation Institute of Cádiz, Puerta del Mar University Hospital, Av/Ana de Viya 21, 11009 Cádiz, Spain
4
BioLab, Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, C/Astrofísico Francisco Sánchez 2, 38206 La Laguna, Spain
5
Instituto de Investigaciones Químicas, CSIC-University of Seville, Américo Vespucio 49, 41092 Sevilla, Spain
*
Author to whom correspondence should be addressed.
Molecules 2021, 26(24), 7501; https://doi.org/10.3390/molecules26247501
Submission received: 5 November 2021 / Revised: 5 December 2021 / Accepted: 8 December 2021 / Published: 11 December 2021
(This article belongs to the Section Bioorganic Chemistry)
Browse Figures
Versions Notes

Abstract

sp2-Iminosugar glycolipids (sp2-IGLs) represent a consolidated family of glycoconjugate mimetics encompassing a monosaccharide-like glycone moiety with a pseudoamide-type nitrogen replacing the endocyclic oxygen atom of carbohydrates and an axially-oriented lipid chain anchored at the pseudoanomeric position. The combination of these structural features makes them promising candidates for the treatment of a variety of conditions, spanning from cancer and inflammatory disorders to parasite infections. The exacerbated anomeric effect associated to the putative sp2-hybridized N-atom imparts chemical and enzymatic stability to sp2-IGLs and warrants total α-anomeric stereoselectivity in the key glycoconjugation step. A variety of O-, N-, C- and S-pseudoglycosides, differing in glycone configurational patterns and lipid nature, have been previously prepared and evaluated. Here we expand the chemical space of sp2-IGLs by reporting the synthesis of α-d-gluco-configured analogs with a bicyclic (5N,6O-oxomethylidene)nojirimycin (ONJ) core incorporating selenium at the glycosidic position. Structure–activity relationship studies in three different scenarios, namely cancer, Leishmaniasis and inflammation, convey that the therapeutic potential of the sp2-IGLs is highly dependent, not only on the length of the lipid chain (linear aliphatic C12 vs. C8), but also on the nature of the glycosidic atom (nitrogen vs. sulfur vs. selenium). The ensemble of results highlights the α-dodecylseleno-ONJ-glycoside as a promising multitarget drug candidate.
Keywords: seleno-sp2-iminoglycolipids; multitarget; immunomodulation; cancer; Leishmania; inflammation seleno-sp2-iminoglycolipids; multitarget; immunomodulation; cancer; Leishmania; inflammation

Share and Cite

MDPI and ACS Style

Sánchez-Fernández, E.M.; García-Hernández, R.; Gamarro, F.; Arroba, A.I.; Aguilar-Diosdado, M.; Padrón, J.M.; García Fernández, J.M.; Ortiz Mellet, C. Synthesis of sp2-Iminosugar Selenoglycolipids as Multitarget Drug Candidates with Antiproliferative, Leishmanicidal and Anti-Inflammatory Properties. Molecules 2021, 26, 7501. https://doi.org/10.3390/molecules26247501

AMA Style

Sánchez-Fernández EM, García-Hernández R, Gamarro F, Arroba AI, Aguilar-Diosdado M, Padrón JM, García Fernández JM, Ortiz Mellet C. Synthesis of sp2-Iminosugar Selenoglycolipids as Multitarget Drug Candidates with Antiproliferative, Leishmanicidal and Anti-Inflammatory Properties. Molecules. 2021; 26(24):7501. https://doi.org/10.3390/molecules26247501

Chicago/Turabian Style

Sánchez-Fernández, Elena M., Raquel García-Hernández, Francisco Gamarro, Ana I. Arroba, Manuel Aguilar-Diosdado, José M. Padrón, José M. García Fernández, and Carmen Ortiz Mellet. 2021. "Synthesis of sp2-Iminosugar Selenoglycolipids as Multitarget Drug Candidates with Antiproliferative, Leishmanicidal and Anti-Inflammatory Properties" Molecules 26, no. 24: 7501. https://doi.org/10.3390/molecules26247501

APA Style

Sánchez-Fernández, E. M., García-Hernández, R., Gamarro, F., Arroba, A. I., Aguilar-Diosdado, M., Padrón, J. M., García Fernández, J. M., & Ortiz Mellet, C. (2021). Synthesis of sp2-Iminosugar Selenoglycolipids as Multitarget Drug Candidates with Antiproliferative, Leishmanicidal and Anti-Inflammatory Properties. Molecules, 26(24), 7501. https://doi.org/10.3390/molecules26247501

Article Metrics

Back to TopTop