Exploring Novel Drug Combinations: The Therapeutic Potential of Selanyl Derivatives for Leishmania Treatment

This work describes the design, synthesis, and biological activities of new selenoester derivatives and its homologs thioesters. Thirty-two compounds were developed following an economical synthetic route, achieving small molecules, with structural characteristics similar to those present in antilei...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2023-08, Vol.28 (15), p.5845
Main Authors: Henriquez-Figuereo, Andreina, Moreno, Esther, Sanmartin, Carmen, Plano, Daniel
Format: Article
Language:English
Subjects:
Acids
Amphotericin B - pharmacology
Amphotericin B - therapeutic use
Animals
Antiprotozoal Agents - therapeutic use
Drug Combinations
Drug therapy, Combination
drug-combination
Drugs
Economic development
Health aspects
Humans
Immune system
Leishmania
Leishmania infantum
Leishmaniasis
Leishmaniasis, Visceral - drug therapy
Mice
Mice, Inbred BALB C
NMR
Nuclear magnetic resonance
Parasites
Parasitic diseases
Paromomycin - pharmacology
selanyl
Selenium
Spain
synergy
Texas
Toxicity
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Summary:This work describes the design, synthesis, and biological activities of new selenoester derivatives and its homologs thioesters. Thirty-two compounds were developed following an economical synthetic route, achieving small molecules, with structural characteristics similar to those present in antileishmanial drugs such as miltefosine (MIL) and paromomycin (PMN). These compounds were tested in vitro against strains of ( ) and ( ). The strain (causative agent of visceral leishmaniasis) exhibited the highest sensitivity. Thus, four selanylacetic acid derivatives ( and ) presented IC values below 40 µM in this strain. These derivatives also demonstrated low toxicity and high selectivity in PMA-differentiated THP-1 macrophages. The - and derivatives were evaluated in order to determine their pharmacological behavior, using drug combination studies with the reference drugs amphotericin B (AMB), MIL and PMN. Compounds and presented a potent synergistic interaction with MIL, which is the only oral drug available for the treatment of visceral leishmaniasis. Therefore, compounds and present significant potential as therapeutic candidates for the treatment of leishmaniasis based on their remarkable leishmanicidal characteristics and pharmacological synergism.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules28155845