HIV aspartyl protease inhibitors as promising compounds against<i>Candida albicans</i>André Luis Souza dos Santos

Santos, André Luis Souza dos

doi:10.4331/wjbc.v1.i2.21

Cited by 31 publications

(34 citation statements)

References 112 publications

(103 reference statements)

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“…As previously described [1,6], SAP4-6 strongly impacts full-virulence of C. albicans phenotype in systemic infections. By using the genetic alternations in SAP4-6 we tested whether these aspartic proteases could have an impact on C. albicans' resistance to the tested sulfones.…”

Section: Discussionmentioning

confidence: 99%

“…Thus the inhibition of Saps represents a promising strategy for the design of anti-virulence drugs, especially in view of the alarming rise in life-threatening systemic fungal infections [5,6]. The blockage of C. albicans Saps should inactivate the pathogen and hence attenuate the infection [5,6]. Therefore, potent Sap inhibitors have been proposed as novel antimycotic agents for the treatment of candidiasis [7].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, these genes are co-ordinately regulated depending on the cellular morphology, that is, yeast or hyphae, which are also important in C. albicans adhesion and biofilm development [4]. Thus the inhibition of Saps represents a promising strategy for the design of anti-virulence drugs, especially in view of the alarming rise in life-threatening systemic fungal infections [5,6]. The blockage of C. albicans Saps should inactivate the pathogen and hence attenuate the infection [5,6].…”

Section: Introductionmentioning

confidence: 99%

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Susceptibility of Candida albicans to New Synthetic Sulfone Derivatives

Staniszewska

Bondaryk

Ochal

2015

Archiv der Pharmazie

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The influence of halogenated methyl sulfones, i.e. bromodichloromethyl-4-chloro-3-nitrophenyl sulfone (named halogenated methyl sulfone 1), dichloromethyl-4-chloro-3-nitrophenyl sulfone (halogenated methyl sulfone 2), and chlorodibromomethyl-4-hydrazino-3-nitrophenyl sulfone (halogenated methyl sulfone 3), on cell growth inhibition, aspartic protease gene (SAP4-6) expression, adhesion to epithelium, and filamentation was investigated. Antifungal susceptibility of the halogenated methyl sulfones was determined with the M27-A3 protocol in the range of 16-0.0313 µg/mL. Adherence to Caco-2 cells was performed in 24-well plates; relative quantification was normalized against ACT1 in cells after 18 h of growth in YEPD and on Caco-2 cells. SAP4-6 expression was analyzed using RT-PCR. Structure-activity relationship studies suggested that halogenated methyl sulfone 1 containing bromodichloromethyl or dichloromethyl function at C-4 (halogenated methyl sulfone 2) of the phenyl ring showed the best activity (100% cell inhibition at 0.5 µg/mL), while hydrazine at C-1 (halogenated methyl sulfone 3) reduced the sulfone potential (100% = 4 µg/mL). SAP4-6 were up- or down-regulated depending on the strains' genetic background and the substitutions on the phenyl ring. Halogenated methyl sulfone 2 repressed germination and affected adherence to epithelium (P ≤ 0.05). The tested halogenated methyl sulfones interfered with the adhesion of Candida albicans cells to the epithelial tissues, without affecting their viability after 90 min of incubation. The mode of action of the halogenated methyl sulfones was attributed to the reduced virulence of C. albicans. SAP5 and SAP6 contribute to halogenated methyl sulfones resistance. Thus, halogenated methyl sulfones can inhibit biofilm formation due to their interference with adherence and with the yeast-to-hyphae transition.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Susceptibility of Candida albicans to New Synthetic Sulfone Derivatives

Staniszewska

Bondaryk

Ochal

2015

Archiv der Pharmazie

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“…Extracellular proteases of eukaryotic microbial pathogens have received tremendous research interest as potential drug targets for pharmaceutical intervention (Dash et al, 2003;Dos Santos, 2010). Analysis of proteolytic enzymes of pathogenic micro-organisms might lead to the design of inhibitors to control these pathogens (Dos Santos, 2011).…”

Section: Discussionmentioning

confidence: 99%

A low-molecular-mass aspartic protease inhibitor from a novel Penicillium sp.: implications in combating fungal infections

Menon

Rao

2012

Microbiology

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“…are associated with a high morbidity and mortality (30-80 % of cases) and therefore remain a major problem worldwide. Thus, the pathogenic adaptation of C. albicans has been the topic of extensive investigations (Dos Santos, 2010;Eggimann et al, 2011). Like most pathogens, C. albicans possess a set of attributes that help the fungal cells to escape the host immune responses and cause a successful infection.…”

Section: Introductionmentioning

confidence: 99%

Comparison of anti-Candida albicans activities of halogenomethylsulfonyl derivatives

2014

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A rapidly growing resistance of Candida spp. requires a search for bioactive compounds with fungicidal or fungistatic activity. In this context a characteristics and comparison of antifungal properties of 19 sulfone derivatives were conducted. MICs of the Compounds were determined using the M27-A3 protocol following CLSI recommendations. The SAP expression was analyzed using RT-PCR; relative quantification was normalized against ACT1 in cells grown in YEPD and on Caco-2. 79 % of sulfone derivatives (15 out of 19) exhibited an activity against Candida albicans in the tested concentrations. While the addition of both chlorine and bromine atoms to halogenomethylsulfonyl groups stimulates sulfone's antifungal activity, a chlorine atom more effectively up-regulates antifungal properties of the tested sulfones. The insertion of a fluorine atom has a binary effect on antifungal properties of the tested sulfones. The fluorine atom enhances anti-Candida properties when introduced to the aromatic ring, while its presence in halogenomethylsulfonyl group generally lowers the Compound's efficiency. The deletion of particular SAP genes resulted in an increased susceptibility of C. albicans toward sulfones indicating the role of this gene family in resistance mechanisms. Furthermore, RT-PCR analysis demonstrated that sulfone derivatives inhibit the SAP2 expression but not that of SAP7.

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HIV aspartyl protease inhibitors as promising compounds againstCandida albicansAndré Luis Souza dos Santos

Cited by 31 publications

References 112 publications

Susceptibility of Candida albicans to New Synthetic Sulfone Derivatives

Susceptibility of Candida albicans to New Synthetic Sulfone Derivatives

A low-molecular-mass aspartic protease inhibitor from a novel Penicillium sp.: implications in combating fungal infections

Comparison of anti-Candida albicans activities of halogenomethylsulfonyl derivatives

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