RESEARCH ARTICLE


Synthesis, Characterization and Antifungal Assessment of Optically Active Bis-organotin Compounds Derived from (S)-BINOL Diesters



Andrea R. Costantino1, Jörg M. Neudörfl2, Romina A. Ocampo1, Laura A. Svetaz3, Susana A. Zacchino3, Liliana C. Koll1, Sandra D. Mandolesi1, *
1 INQUISUR, Departamento de Química, Universidad Nacional del Sur (UNS)- CONICET, Av. Alem 1253, 8000 Bahía Blanca, Argentina
2 Farmacognosia, Facultad de Cs. Bioquímicas y Farmacéuticas, Suipacha 531- 2000 Rosario, Argentina
3 Institute of Organic Chemistry, Department of Chemistry, University of Cologne, Greinstr. 4, D-50939 Cologne, Germany


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© 2019 Costantino et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of INQUISUR, Departamento de Química, Universidad Nacional del Sur (UNS)- CONICET, Av. Alem 1253, 8000 Bahía Blanca, Argentina; Tel: +54-291-459-5101;
Fax: +54-291-459-5187; Email: sdmando@criba.edu.ar


Abstract

Background:

Organotin(IV) derivatives have appeared recently as potential biologically active metallopharmaceuticals exhibiting a variety of therapeutic activities. Hence, it is important to study the synthesis of new organotin compounds with low toxicity that may be of pharmacological interest.

Objectives:

This study focuses on the synthesis of new bis-stannylated derivatives with C2 symmetry that could be tested as antifungal agents against two clinical important fungal species, Cryptococcus neoformans and Candida albicans.

Methods:

The radical addition of triorganotin hydrides (R3SnH) and diorganotin chlorohydrides (R2ClSnH) to bis-α,β-unsaturated diesters derived from (S)-BINOL led to the corresponding new bis-stannylated derivatives with C2 symmetry. Nine pure organotin compounds were synthesized with defined stereochemistry. Four of them were enantiomerically pure and four were diastereoisomeric mixtures.

Results:

All new organotin compounds were fully characterized, those with phenyl ligands bonded to tin were the most active compounds against both the strains (Cryptococcus neoformans and Candida albicans), with activity parameters of IC50 close to those of the reference drug (amphotericin B).

Conclusion:

Nine pure organotin compounds with C2 symmetry were synthesized with defined stereochemistry and their antifungal properties were tested against two clinical important fungi with IC values close to those of the reference drug. The structure-containing preferably two or three phenyl groups joined to the tin atom were highly active against both the strains compared with those possessing tri-n-butyl groups.

Keywords: C2 symmetry, Bis-stannylated (S)-BINOL derivatives, Bis-chlorostannanes, Radical hydrostannation, Cryptococcus neoformans, Cryptococcus neoformans.