Inhibition of Leishmania mexicana growth by the tuberculosis drug SQ109

Verónica García-García; Eric Oldfield; Gustavo Benaim

doi:10.1128/AAC.00945-16

Inhibition of Leishmania mexicana growth by the tuberculosis drug SQ109

Verónica García-García, Eric Oldfield, Gustavo Benaim

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

We report that the tuberculosis drug SQ109 [N-adamantan-2-yl-N′-((E)-3,7-dimethyl-octa-2,6-dienyl)-ethane-1,2-diamine] has potent activity against the intracellular amastigote form of Leishmania mexicana (50% inhibitory concentration [IC₅₀], ∼11 nM), with a good selectivity index (>500). It is also active against promastigotes (IC₅₀, ∼500 nM) and acts as a protonophore uncoupler, in addition to disrupting Ca²⁺ homeostasis by releasing organelle Ca²⁺ into the cytoplasm, and as such, it is an interesting new leishmaniasis drug hit candidate.

Original language	English (US)
Pages (from-to)	6386-6389
Number of pages	4
Journal	Antimicrobial Agents and Chemotherapy
Volume	60
Issue number	10
DOIs	https://doi.org/10.1128/AAC.00945-16
State	Published - Oct 2016

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

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@article{9e1db19ffcba4e278f1aca0708b937bf,

title = "Inhibition of Leishmania mexicana growth by the tuberculosis drug SQ109",

abstract = "We report that the tuberculosis drug SQ109 [N-adamantan-2-yl-N′-((E)-3,7-dimethyl-octa-2,6-dienyl)-ethane-1,2-diamine] has potent activity against the intracellular amastigote form of Leishmania mexicana (50% inhibitory concentration [IC50], ∼11 nM), with a good selectivity index (>500). It is also active against promastigotes (IC50, ∼500 nM) and acts as a protonophore uncoupler, in addition to disrupting Ca2+ homeostasis by releasing organelle Ca2+ into the cytoplasm, and as such, it is an interesting new leishmaniasis drug hit candidate.",

author = "Ver{\'o}nica Garc{\'i}a-Garc{\'i}a and Eric Oldfield and Gustavo Benaim",

note = "Funding Information: We thank Otto Geoffroy, Alchem Laboratories Corporation, for providing the SQ109. This work was supported by the Fondo Nacional de Ciencias, Tecnolog?a e Investigaci?n, Venezuela (FONACIT; grant 2011000884 to G.B.), by the Consejo de Desarrollo Cient?fico y Human?stico-Universidad Central de Venezuela (CDCH-UCV; grant PG-03-8728-2013/2 to G.B.), and in part by the U.S. Public Health Service (NIH grants CA158191 and GM065307 to E.O.), a Harriet A. Harlin Professorship (E.O.), and the University of Illinois Foundation/Oldfield Research Fund.",

year = "2016",

month = oct,

doi = "10.1128/AAC.00945-16",

language = "English (US)",

volume = "60",

pages = "6386--6389",

journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

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AU - García-García, Verónica

AU - Oldfield, Eric

AU - Benaim, Gustavo

N1 - Funding Information: We thank Otto Geoffroy, Alchem Laboratories Corporation, for providing the SQ109. This work was supported by the Fondo Nacional de Ciencias, Tecnolog?a e Investigaci?n, Venezuela (FONACIT; grant 2011000884 to G.B.), by the Consejo de Desarrollo Cient?fico y Human?stico-Universidad Central de Venezuela (CDCH-UCV; grant PG-03-8728-2013/2 to G.B.), and in part by the U.S. Public Health Service (NIH grants CA158191 and GM065307 to E.O.), a Harriet A. Harlin Professorship (E.O.), and the University of Illinois Foundation/Oldfield Research Fund.

PY - 2016/10

Y1 - 2016/10

N2 - We report that the tuberculosis drug SQ109 [N-adamantan-2-yl-N′-((E)-3,7-dimethyl-octa-2,6-dienyl)-ethane-1,2-diamine] has potent activity against the intracellular amastigote form of Leishmania mexicana (50% inhibitory concentration [IC50], ∼11 nM), with a good selectivity index (>500). It is also active against promastigotes (IC50, ∼500 nM) and acts as a protonophore uncoupler, in addition to disrupting Ca2+ homeostasis by releasing organelle Ca2+ into the cytoplasm, and as such, it is an interesting new leishmaniasis drug hit candidate.

AB - We report that the tuberculosis drug SQ109 [N-adamantan-2-yl-N′-((E)-3,7-dimethyl-octa-2,6-dienyl)-ethane-1,2-diamine] has potent activity against the intracellular amastigote form of Leishmania mexicana (50% inhibitory concentration [IC50], ∼11 nM), with a good selectivity index (>500). It is also active against promastigotes (IC50, ∼500 nM) and acts as a protonophore uncoupler, in addition to disrupting Ca2+ homeostasis by releasing organelle Ca2+ into the cytoplasm, and as such, it is an interesting new leishmaniasis drug hit candidate.

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