Small molecule anion transporters display <i>in vitro</i> antimicrobial activity against clinically relevant bacterial strains

Carreira-Barral, Israel; Rumbo, Carlos; Mielczarek, Marcin; Alonso-Carrillo, Daniel; Herrán, Enara; Pastor, Marta; Pozo, Ángel del; Garcı́a-Valverde, Marı́a; Quesada, Roberto

doi:10.1039/c9cc04304g

Cited by 39 publications

(52 citation statements)

References 31 publications

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“…Benznidazole (BNZ, Laboratorios ELEA, Buenos Aires, Argentina) was used as the reference drug. Tambjamine analogs, Obatoclax, and synthetic prodigiosin (prepared as a hydrochloride salt) were synthesized as reported elsewhere [ 27 , 28 , 29 ]. Natural prodigiosin was obtained as previously described [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

Tambjamines and Prodiginines: Biocidal Activity against Trypanosoma cruzi

et al. 2021

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The aim of this work was to explore new therapeutic options against Chagas disease by the in vitro analysis of the biocidal activities of several tambjamine and prodiginine derivatives, against the Trypanosoma cruzi CLB strain (DTU TcVI). The compounds were initially screened against epimastigotes. The five more active compounds were assayed in intracellular forms. The tambjamine MM3 and both synthetic and natural prodigiosins displayed the highest trypanocidal profiles, with IC50 values of 4.52, 0.46, and 0.54 µM for epimastigotes and 1.9, 0.57, and 0.1 µM for trypomastigotes/amastigotes, respectively. Moreover, the combination treatment of these molecules with benznidazole showed no synergism. Finally, oxygen consumption inhibition determinations performed using high-resolution respirometry, revealed a potent effect of prodigiosin on parasite respiration (73% of inhibition at ½ IC50), suggesting that its mode of action involves the mitochondria. Moreover, its promising selectivity index (50) pointed out an interesting trypanocidal potential and highlighted the value of prodigiosin as a new candidate to fight Chagas disease.

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Section: Methodsmentioning

confidence: 99%

Tambjamines and Prodiginines: Biocidal Activity against Trypanosoma cruzi

et al. 2021

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“…In compounds 28a-d one of the pyrrole groups of the 4-methoxy-2,2'-bipyrrole core present in natural tambjamines was replaced by an indole ring, and in compounds 28d and 29a-c the indole was inserted as a substituent of the enamine group. 75,76 Compounds 30a-i were named click tambjamines, due to the presence of a triazole ring that replaced one of the pyrrole rings in the natural predecessors. This permitted to explore structural changes by straightforward functionalization at both the triazole ring and the imine/enamine moiety.…”

Section: Cationic Transportersmentioning

confidence: 99%

Transmembrane transport of bicarbonate by anion receptors

Martínez‐Crespo

Valkenier

2022

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The development of synthetic anion transporters is motivated by their potential application as treatment for diseases that originate from deficient anion transport by natural proteins. Transport of bicarbonate is important for crucial biological functions such as respiration and digestion. Despite this biological relevance, bicarbonate transport has not been as widely studied as chloride transport. Herein we present an overview of the synthetic receptors that have been studied as bicarbonate transporters, together with the different assays used to perform transport studies in large unilamellar vesicles. We highlight the most active transporters and comment on the nature of the functional groups present in active and inactive compounds. We also address recent mechanistic studies that have revealed different processes that can lead to net transport of bicarbonate, as well as studies reported in cells and tissues and comment on the key challenges for the further development of bicarbonate transporters.

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“…2 These innovations include the development of ionophores that can selectively insert into and permeabilise Gram-positive (such as Staphylococcus aureus) and Gramnegative such as Escherichia coli) bacterial membranes enabling the movement of ions across cell membranes, triggering cell death. [3][4][5][6][7][8][9] Recently reported examples of small molecule K + and Na + transporters have commonly utilised macrocycles such as crown ethers [10][11][12][13][14][15][16][17][18][19][20] and strapped calix [4]pyrrole moieties. 21 However, a limitation of many supramolecular ionophores designed for therapeutic applications is their high lipophilicity, making them poorly water soluble, thus limiting the translation of this molecular technology into the clinic.…”

Section: Main Article Textmentioning

confidence: 99%

Cooperative cation co-transport by supramolecular self-associating amphiphiles

Yang

Boles

White

et al. 2021

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We report investigations into the cation transport ability of a series of antimicrobial supramolecular, self-associating amphiphiles (SSAs). The SSAs proved to be challenging to study using standard, literature assays and we therefore describe a novel methodology to examine cation transport via a chloride co-transport assay. One SSA in this series was observed to function as a K+ and Na+ transporter with promising deliverability properties. The results shed light on a potential mechanism of microbial toxicity and inform the design of future targets.

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Small molecule anion transporters display in vitro antimicrobial activity against clinically relevant bacterial strains

Abstract: Highly active transmembrane anion transporters have demonstrated their activity against antibiotic-resistant and clinically relevant bacterial strains.

Cited by 39 publications

References 31 publications

Tambjamines and Prodiginines: Biocidal Activity against Trypanosoma cruzi

Tambjamines and Prodiginines: Biocidal Activity against Trypanosoma cruzi

Transmembrane transport of bicarbonate by anion receptors

Cooperative cation co-transport by supramolecular self-associating amphiphiles

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