Literature DB >> 27458218

Inhibition of Leishmania mexicana Growth by the Tuberculosis Drug SQ109.

Verónica García-García1, Eric Oldfield2, Gustavo Benaim3.   

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 Ca(2+) homeostasis by releasing organelle Ca(2+) into the cytoplasm, and as such, it is an interesting new leishmaniasis drug hit candidate.
Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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Year:  2016        PMID： 27458218      PMCID： PMC5038243          DOI： 10.1128/AAC.00945-16

Source DB:  PubMed          Journal:  Antimicrob Agents Chemother        ISSN： 0066-4804            Impact factor:   5.191


  16 in total

1.  SQ109, a new drug lead for Chagas disease.

Authors:  Phercyles Veiga-Santos; Kai Li; Lilianne Lameira; Tecia Maria Ulisses de Carvalho; Guozhong Huang; Melina Galizzi; Na Shang; Qian Li; Dolores Gonzalez-Pacanowska; Vanessa Hernandez-Rodriguez; Gustavo Benaim; Rey-Ting Guo; Julio A Urbina; Roberto Docampo; Wanderley de Souza; Eric Oldfield
Journal:  Antimicrob Agents Chemother       Date:  2015-01-12       Impact factor: 5.191

Review 2.  The emerging role of amiodarone and dronedarone in Chagas disease.

Authors:  Gustavo Benaim; Alberto E Paniz Mondolfi
Journal:  Nat Rev Cardiol       Date:  2012-08-07       Impact factor: 32.419

3.  In vitro anti-Trypanosoma cruzi activity of dronedarone, a novel amiodarone derivative with an improved safety profile.

Authors:  Gustavo Benaim; Vanessa Hernandez-Rodriguez; Sheira Mujica-Gonzalez; Lourdes Plaza-Rojas; May Li Silva; Nereida Parra-Gimenez; Yael Garcia-Marchan; Alberto Paniz-Mondolfi; Graciela Uzcanga
Journal:  Antimicrob Agents Chemother       Date:  2012-04-16       Impact factor: 5.191

4.  Novel insights into the mechanism of inhibition of MmpL3, a target of multiple pharmacophores in Mycobacterium tuberculosis.

Authors:  Wei Li; Ashutosh Upadhyay; Fabio L Fontes; E Jeffrey North; Yuehong Wang; Debbie C Crans; Anna E Grzegorzewicz; Victoria Jones; Scott G Franzblau; Richard E Lee; Dean C Crick; Mary Jackson
Journal:  Antimicrob Agents Chemother       Date:  2014-08-18       Impact factor: 5.191

5.  Nitazoxanide Disrupts Membrane Potential and Intrabacterial pH Homeostasis of Mycobacterium tuberculosis.

Authors:  Luiz Pedro S de Carvalho; Crystal M Darby; Kyu Y Rhee; Carl Nathan
Journal:  ACS Med Chem Lett       Date:  2011       Impact factor: 4.345

6.  Amiodarone and itraconazole: a rational therapeutic approach for the treatment of chronic Chagas' disease.

Authors:  A E Paniz-Mondolfi; A M Pérez-Alvarez; G Lanza; E Márquez; J L Concepción
Journal:  Chemotherapy       Date:  2009-05-19       Impact factor: 2.544

7.  Dronedarone, an amiodarone analog with improved anti-Leishmania mexicana efficacy.

Authors:  Gustavo Benaim; Paola Casanova; Vanessa Hernandez-Rodriguez; Sheira Mujica-Gonzalez; Nereida Parra-Gimenez; Lourdes Plaza-Rojas; Juan Luis Concepcion; Yi-Liang Liu; Eric Oldfield; Alberto Paniz-Mondolfi; Alirica I Suarez
Journal:  Antimicrob Agents Chemother       Date:  2014-02-03       Impact factor: 5.191

8.  Antiinfectives targeting enzymes and the proton motive force.

Authors:  Xinxin Feng; Wei Zhu; Lici A Schurig-Briccio; Steffen Lindert; Carolyn Shoen; Reese Hitchings; Jikun Li; Yang Wang; Noman Baig; Tianhui Zhou; Boo Kyung Kim; Dean C Crick; Michael Cynamon; J Andrew McCammon; Robert B Gennis; Eric Oldfield
Journal:  Proc Natl Acad Sci U S A       Date:  2015-12-07       Impact factor: 11.205

9.  Amiodarone destabilizes intracellular Ca2+ homeostasis and biosynthesis of sterols in Leishmania mexicana.

Authors:  Xenón Serrano-Martín; Yael García-Marchan; Alexis Fernandez; Noris Rodriguez; Hector Rojas; Gonzalo Visbal; Gustavo Benaim
Journal:  Antimicrob Agents Chemother       Date:  2009-01-21       Impact factor: 5.191

10.  Multitarget drug discovery for tuberculosis and other infectious diseases.

Authors:  Kai Li; Lici A Schurig-Briccio; Xinxin Feng; Ashutosh Upadhyay; Venugopal Pujari; Benoit Lechartier; Fabio L Fontes; Hongliang Yang; Guodong Rao; Wei Zhu; Anmol Gulati; Joo Hwan No; Giovana Cintra; Shannon Bogue; Yi-Liang Liu; Katie Molohon; Peter Orlean; Douglas A Mitchell; Lucio Freitas-Junior; Feifei Ren; Hong Sun; Tong Jiang; Yujie Li; Rey-Ting Guo; Stewart T Cole; Robert B Gennis; Dean C Crick; Eric Oldfield
Journal:  J Med Chem       Date:  2014-04-01       Impact factor: 7.446
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  10 in total

1.  Identification of New MmpL3 Inhibitors by Untargeted and Targeted Mutant Screens Defines MmpL3 Domains with Differential Resistance.

Authors:  John T Williams; Elizabeth R Haiderer; Garry B Coulson; Kayla N Conner; Edmund Ellsworth; Chao Chen; Nadine Alvarez-Cabrera; Wei Li; Mary Jackson; Thomas Dick; Robert B Abramovitch
Journal:  Antimicrob Agents Chemother       Date:  2019-09-23       Impact factor: 5.191

2.  Mechanism of Action of Miltefosine on Leishmania donovani Involves the Impairment of Acidocalcisome Function and the Activation of the Sphingosine-Dependent Plasma Membrane Ca2+ Channel.

Authors:  Andrea K Pinto-Martinez; Jessica Rodriguez-Durán; Xenon Serrano-Martin; Vanessa Hernandez-Rodriguez; Gustavo Benaim
Journal:  Antimicrob Agents Chemother       Date:  2017-12-21       Impact factor: 5.191

3.  SQ109 inhibits proliferation of Leishmania donovani by disruption of intracellular Ca2+ homeostasis, collapsing the mitochondrial electrochemical potential (ΔΨm) and affecting acidocalcisomes.

Authors:  Zain Gil; Nathalia Martinez-Sotillo; Andrea Pinto-Martinez; Fabiola Mejias; Juan Carlos Martinez; Ivan Galindo; Eric Oldfield; Gustavo Benaim
Journal:  Parasitol Res       Date:  2020-01-02       Impact factor: 2.289

4.  Determination of Intracellular Ca2+ Concentration in the Human Pathogens Trypanosomatids Leishmania mexicana and Trypanosoma cruzi by the Use of the Fluorescent Ca2+ Indicator Fura-2.

Authors:  André Rey-Cibati; Mariana Valladares-Delgado; Gustavo Benaim
Journal:  Bio Protoc       Date:  2020-09-20

Review 5.  Disruption of Intracellular Calcium Homeostasis as a Therapeutic Target Against Trypanosoma cruzi.

Authors:  Gustavo Benaim; Alberto E Paniz-Mondolfi; Emilia Mia Sordillo; Nathalia Martinez-Sotillo
Journal:  Front Cell Infect Microbiol       Date:  2020-02-14       Impact factor: 5.293

6.  The multi-target aspect of an MmpL3 inhibitor: The BM212 series of compounds bind EthR2, a transcriptional regulator of ethionamide activation.

Authors:  Alice R Moorey; Alejandro Cabanillas; Sarah M Batt; Sonja Ghidelli-Disse; Beatriz Urones; Olalla Sanz; Joel Lelievre; Marcus Bantscheff; Liam R Cox; Gurdyal S Besra
Journal:  Cell Surf       Date:  2021-11-23

7.  Fifty Years of Research on Protonophores: Mitochondrial Uncoupling As a Basis for Therapeutic Action.

Authors:  E A Kotova; Y N Antonenko
Journal:  Acta Naturae       Date:  2022 Jan-Mar       Impact factor: 2.204

8.  Hydroxylation of Antitubercular Drug Candidate, SQ109, by Mycobacterial Cytochrome P450.

Authors:  Sergey Bukhdruker; Tatsiana Varaksa; Irina Grabovec; Egor Marin; Polina Shabunya; Maria Kadukova; Sergei Grudinin; Anton Kavaleuski; Anastasiia Gusach; Andrei Gilep; Valentin Borshchevskiy; Natallia Strushkevich
Journal:  Int J Mol Sci       Date:  2020-10-16       Impact factor: 5.923

9.  In Vivo Efficacy of SQ109 against Leishmania donovani, Trypanosoma spp. and Toxoplasma gondii and In Vitro Activity of SQ109 Metabolites.

Authors:  Kyung-Hwa Baek; Trong-Nhat Phan; Satish R Malwal; Hyeryon Lee; Zhu-Hong Li; Silvia N J Moreno; Eric Oldfield; Joo Hwan No
Journal:  Biomedicines       Date:  2022-03-14

10.  Structure, In Vivo Detection, and Antibacterial Activity of Metabolites of SQ109, an Anti-Infective Drug Candidate.

Authors:  Satish R Malwal; Matthew D Zimmerman; Nadine Alvarez; Jansy P Sarathy; Véronique Dartois; Carol A Nacy; Eric Oldfield
Journal:  ACS Infect Dis       Date:  2021-07-19       Impact factor: 5.084
  10 in total

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