Novel cyclam multicomponent crystal forms: synthesis, characterization and antimicrobial activity

Saied, Rajaa; Alves, Paula C.; Rijo, Patrícia; André, Vânia; Alves, Luis G.

doi:10.1039/d3ce00354j

Cited by 3 publications

(3 citation statements)

References 42 publications

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“…Cyclams are macrocyclic polyamines which have demonstrated medical interest, namely as antibacterial, antifungal and antiparasitic agents [18][19][20][21][22][23][24][25][26]. The cyclam salt H 4 [H 2 ( 4-CF3 PhCH 2 ) 2 Cyclam]Cl 4 (compound 1) was previously studied against C. krusei and C. albicans, and demonstrated a relevant antifungal activity, with minimal inhibitory concentration (MIC) values of 8 µg/mL for C. krusei and of 128 µg/mL for C. albicans [7].…”

Section: Discussionmentioning

confidence: 99%

Disclosing the Antifungal Mechanisms of the Cyclam Salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 against Candida albicans and Candida krusei

Costa,

Lopes,

Morais

et al. 2024

IJMS

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Mycoses are one of the major causes of morbidity/mortality among immunocompromised individuals. Considering the importance of these infections, the World Health Organization (WHO) defined a priority list of fungi for health in 2022 that include Candida albicans as belonging to the critical priority group and Pichia kudriavzevii (Candida krusei) to the medium priority group. The existence of few available antifungal drugs, their high toxicity, the acquired fungal resistance, and the appearance of new species with a broader spectrum of resistance, points out the need for searching for new antifungals, preferably with new and multiple mechanisms of action. The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 was previously tested against several fungi and revealed an interesting activity, with minimal inhibitory concentration (MIC) values of 8 µg/mL for C. krusei and of 128 µg/mL for C. albicans. The main objective of the present work was to deeply understand the mechanisms involved in its antifungal activity. The effects of the cyclam salt on yeast metabolic viability (resazurin reduction assay), yeast mitochondrial function (JC-1 probe), production of reactive oxygen species (DCFH-DA probe) and on intracellular ATP levels (luciferin/luciferase assay) were evaluated. H4[H2(4-CF3PhCH2)2Cyclam]Cl4 induced a significant decrease in the metabolic activity of both C. albicans and C. krusei, an increase in Reactive Oxygen Species (ROS) production, and an impaired mitochondrial function. The latter was observed by the depolarization of the mitochondrial membrane and decrease in ATP intracellular levels, mechanisms that seems to be involved in the antifungal activity of H4[H2(4-CF3PhCH2)2Cyclam]Cl4. The interference of the cyclam salt with human cells revealed a CC50 value against HEK-293 embryonic kidney cells of 1.1 mg/mL and a HC10 value against human red blood cells of 0.8 mg/mL.

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Section: Discussionmentioning

confidence: 99%

Disclosing the Antifungal Mechanisms of the Cyclam Salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 against Candida albicans and Candida krusei

Costa,

Lopes,

Morais

et al. 2024

IJMS

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“…Cyclams are macrocyclic polyamines, the medical interest in which was fueled by the therapeutic potential of a bicyclam derivative against HIV infection, inflammatory diseases, cancer, and stem-cell mobilization [ 1 ]. Taking advantage of their biocompatibility, high metal chelation stability constants, and the possibility of N-functionalization of the cyclam backbone, a variety of cyclam derivatives have been successfully explored in recent years as antibacterial [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ], antifungal [ 7 , 8 , 9 ], and antiparasitic agents [ 10 , 11 , 12 ]. The neamine cyclam derivative (NeaCyclam) was revealed to be highly effective against Escherichia coli and Enterococcus aerogenes , being able to affect the outer membrane stability by altering the permeability barrier [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, the inhibitory effect was maintained against clinical isolates of M. tuberculosis resistant to single or multiple antimycobacterial drugs. A series of trans -disubstituted cyclam salts displaying benzyl groups directly attached to the cyclam ring was found to be active against E. coli and Staphylococcus aureus [ 6 , 7 ]. The results obtained revealed that the position and polarity of the substituents on the benzyl groups attached to the cyclam ring are directly related to the antibacterial activity, with the compound displaying a CF 3 moiety in the para position of the benzyl groups being remarkably active.…”

Section: Introductionmentioning

confidence: 99%

A Cyclam Salt as an Antifungal Agent: Interference with Candida spp. and Cryptococcus neoformans Mechanisms of Virulence

Cerqueira,

Medeiros,

Lopes

et al. 2024

Antibiotics

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The importance of fungal infections, particularly those caused by yeasts, is increasing among the medical community. Candida albicans and Cryptococcus neoformans are amongst the high-priority fungal species identified by the World Health Organization (WHO) and are considered in the critical group, while Candida krusei is included in the medium-priority group. The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 proved to be active against the growth of these three yeasts, and the aim of this work was to verify its interference with their virulence mechanisms, whether shared or unique. H4[H2(4-CF3PhCH2)2Cyclam]Cl4 significantly inhibited biofilm production and catalase activity, being able to interfere with C. albicans dimorphic transition and C. neoformans melanin production. At the minimal inhibitory concentration (MIC) values, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 had no antioxidant effect, as determined by the DPPH method. When using the RAW264.7 macrophage cell line, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 reduced nitric oxide (NO) detection (the Griess reaction), but this effect was associated with a significant toxic effect on the cells.

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Structural characterization of benzoate anion-supported supramolecular assemblages of Co(III) and Ni(II) cyclam compounds with catecholase-like and antibacterial activities

Harmalkar,

Gaonkar,

Barretto

et al. 2024

Inorganica Chimica Acta

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Novel cyclam multicomponent crystal forms: synthesis, characterization and antimicrobial activity

Abstract: Novel multicomponent crystal forms were obtained from reactions of trans-disubstituted cyclam derivatives with flufenamic and salicylic acids.

Cited by 3 publications

References 42 publications

Disclosing the Antifungal Mechanisms of the Cyclam Salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 against Candida albicans and Candida krusei

Disclosing the Antifungal Mechanisms of the Cyclam Salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 against Candida albicans and Candida krusei

A Cyclam Salt as an Antifungal Agent: Interference with Candida spp. and Cryptococcus neoformans Mechanisms of Virulence

Structural characterization of benzoate anion-supported supramolecular assemblages of Co(III) and Ni(II) cyclam compounds with catecholase-like and antibacterial activities

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