Abstract
The pentavalent meglumine antimoniate (MA) is still a first-line drug in the treatment of leishmaniasis in several countries. As an attempt to elucidate its mechanism of action and develop new antimonial drugs with improved therapeutic profile, Sb(V) complexes with different ligands, including β-cyclodextrin (β-CD), nucleosides and non-ionic surfactants, have been studied. Interestingly, Sb(V) oxide, MA, its complex with β-CD, Sb(V)-guanosine complex and amphiphilic Sb(V) complexes with N-alkyl-N-methylglucamide, have shown marked tendency to self-assemble in aqueous solutions, forming nanoaggregates, hydrogel or micelle-like nanoparticles. Surprisingly, the resulting assemblies presented in most cases slow dissociation kinetics upon dilution and a strong influence of pH, which impacted on their pharmacokinetic and therapeutic properties against leishmaniasis. To explain this unique property, we raised the hypothesis that multiple pnictogen bonds could contribute to the formation of these assemblies and their kinetic of dissociation. The present article reviews our current knowledge on the structural organization and physicochemical characteristics of Sb-based supramolecular assemblies, as well as their pharmacological properties and potential for treatment of leishmaniasis. This review supports the feasibility of the rational design of new Sb(V) complexes with supramolecular assemblies for the safe and effective treatment of leishmaniasis.
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Funding
This work was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, grant numbers 425332/2018–7, 306198/2021–5), INCT NanoBiofar (MCTI, CNPq, Brazil), Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG, grant number PPM-00372–17, RED-00202–22, BPD-00276–22), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, grant Combate-COVID1665970P), Région Ile-de-France (DIM1Health) and COST Action (number CA21111). F.F. was recipient of fellowships from CNPq, “Chaire Jean d’Alembert” (IdEx Université Paris-Saclay) and “Chaire d’Excellence DIM1Health” (Région Ile-de-France). G.S.R. and V.M.R.V. were recipient of a studentship from CNPq and CAPES.
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Demicheli, C., Vallejos, V.M.R., Lanza, J.S. et al. Supramolecular assemblies from antimony(V) complexes for the treatment of leishmaniasis. Biophys Rev 15, 751–765 (2023). https://doi.org/10.1007/s12551-023-01073-6
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DOI: https://doi.org/10.1007/s12551-023-01073-6