Piperazine Propanol Derivative as a Novel Antifungal Targeting 1,3-.BETA.-D-Glucan Synthase

Kondoh, Osamu; Inagaki, Yukiko; Fukuda, Hiroshi; Mizuguchi, Eisaku; Ohya, Yoshikazu; Arisawa, Mikio; Shimma, Nobuo; Aoki, Yuko; Sakaitani, Masahiro; Watanabe, T.

doi:10.1248/bpb.28.2138

Cited by 28 publications

(18 citation statements)

References 28 publications

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“…The surveys have confirmed the antimycotic effect of this group of substances (Nastenko et al, 2018). Antifungal effect of this group was studied by Kohdoh et al (2005). They report that the piperazine propanol derivative GSI578 [(2,6-difluoro-phenyl)-carbamic acid 3-(4-benzothiazol-2-yl-piperazine-1-yl)-propyl ester] was identified as a potent inhibitor against 1,3-β-D-glucan synthase.…”

Section: Discussionmentioning

confidence: 92%

“…This enzyme synthesizes the component of the cellular wall of fungus, which is a promising target for antifungal agents. GSI578 exerted in vitro antifungal activity against pathogenic fungi, including C. albicans and Aspergillus fumigatus (Kohdoh et al, 2005). Presence of 4-(1.1.3.3-tetramethylbutyl)phenyl radical was found to be providing the compounds with a broad range of antimicrobial activity.…”

Section: Discussionmentioning

confidence: 97%

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Sensitivity of antifungal preparations of Сandida isolates from sub-biotopes of the human oral cavity

Osypchuk¹,

Nastenko²,

Широбоков³

et al. 2020

Regul. Mech. Biosyst.

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Candidiasis is the commonest opportunistic infection of the oral cavity. As a result of immune-deficiency of the organism, yeasts of Candida genus by acting as commensal organisms transmute into pathogenic organisms. The article presents frequency of isolation, topographic peculiarities, species range, sensitivity of the Candida yeasts to antimycotics and newly-synthesized derivatives of amino alcohols isolated from the sub-biotopes of the oral cavity of patients with oncopathologies. The survey of the material included microscopic, mycologic, statistical-analytical methods. For all the clinical isolates the sensitivity to antifungal preparations was determined. Over the study 492 sub-biotopes of the oral cavity were examined. The extraction of the material was made from the mucous membrane of the cheek, angle of the mouth, mucous membrane of the surface of the tongue and the palate. According to the results of the conducted studies, the level of candidal carriage on the mucous membrane of the oral cavity in the patients with oncopathologies without clinical signs of candidiasis equaled 25.0%, active candidiasis infection was found in 47.0% of cases. Among the clinical strains, we isolated: C. albicans, C. glabrata, C. tropicalis and C. krusei. Among all the isolated strains, in all 4 sub-biotopes C. albicans dominated accounting for 73.1%. In 4 sub-biotopes we detected the association of two species of Candida. Analysis of the obtained results of the susceptibility of strains to modern antymicotics and newly-synthesized substances revealed that the representatives of non-albicans are more resistant to the antifungal preparations. Among the commercial preparations, amphotericin B exerted the highest activity against the clinical isolates of yeast-like fungi. The concentration of 0.97 µg/mL inhibited 50.0% of representatives of non-albicans, and also 75.0% of isolates of C. albicans. Fluconazole exhibited activity in the concentration of 1 µg/mL towards 17.0% of non-albicans and 25.0% of С. albicans. Itraconazole was observed to have no significant antifungal activity. Among the newly-synthesized aryl acyclic amino alcohols, compound Kc22 displayed high activity against both groups of Candida (experimental and control) making it promising for creating new therapeutic preparations. The parameters of resistance of clinical isolates to modern antimycotics indicate the necessity of constant monitoring of the sensitivity of the pathogens of candidiasis and precise species identification for rational use of antifungal preparations and prevention of the development of antimycotic resistance.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 97%

Sensitivity of antifungal preparations of Сandida isolates from sub-biotopes of the human oral cavity

Osypchuk¹,

Nastenko²,

Широбоков³

et al. 2020

Regul. Mech. Biosyst.

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“…Similarly, Aerothricin3/FR901469 is a macrocyclic lipopeptidolactone composed of 12 amino acids and a 3-hydroxypalmitoyl moiety with GS inhibitory activity (Fujie et al, 2001, Kondoh et al, 2002. The piperazine propanol derivative GSI578 [(2,6-Difluoro-phenyl)-carbamic acid 3-(4-benzothiazol-2-ylpiperazine-1-yl)-propyl ester] is a synthetic antifungal drug described as GS inhibitor (Kondoh et al, 2005). Clavariopsins, cyclic depsipeptides lacking a long lipophilic radical, have also been described as inhibitors of glucan synthesis (Kaida et al, 2001).…”

Section: Other Inhibitors Of the Gsmentioning

confidence: 99%

New Cell Wall-Affecting Antifungal Antibiotics

Ribas

Durán

Cortés

2013

Antimicrobial Compounds

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Fungi have emerged worldwide as increasingly frequent causes of healthcareassociated infections. Invasive fungal infections can be life-threatening. However, the number of antifungal agents available and their use in therapy is very limited. Recently, a new family of specific fungal cell wall synthesis inhibitors has emerged as an alternative antifungal therapy and is gaining increasing relevance yearly. The cell wall is a multilayer dynamic structure, essential to the integrity and shape of the fungal cell, whose function is to counteract the osmotic forces that could otherwise produce fungal cell lysis. The cell wall is absent in nonfungal cells, therefore representing a useful target in discovering selective drugs for the treatment of fungal infections without causing toxicity in the host. Although fungi exhibit a considerable diversity in their cell wall structure, all present β(1,3)-, β(1,6)-and α(1,3)-glucans, chitin, and mannoproteins as their major cell wall components. Three different cell wall synthesis inhibitors of the lipopeptide family of echinocandins, named caspofungin, micafungin and anidulafungin, are commercially-available and new classes of cell wall synthesis inhibitors are emerging. This review provides an overview of what is so far known about the different classes of cell wall-affecting antifungal agents and their mechanism of action, offering new alternatives with clinical potential.

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“…Мікробна резистентність до антибіотиків стала серйозною проблемою в боротьбі зі збудниками різних інфекційних захворювань [11]. Останнім часом все частіше виділяють мультирезистентні штами Pseudomonas aeruginosa, що є збудником гнійно-запальних, внутрішньолікарняних та постопераційних інфекцій.…”

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Study of Antimicrobial Activity of Alkyl (R-Aryl) Oxy Dialkyl Ammonium Salts Towards the Reference Strains of Microorganisms

Nastenko¹,

Короткий²,

Смертенко³

et al. 2018

Microbiology&Biotechnology

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Piperazine Propanol Derivative as a Novel Antifungal Targeting 1,3-.BETA.-D-Glucan Synthase

Cited by 28 publications

References 28 publications

Sensitivity of antifungal preparations of Сandida isolates from sub-biotopes of the human oral cavity

Sensitivity of antifungal preparations of Сandida isolates from sub-biotopes of the human oral cavity

New Cell Wall-Affecting Antifungal Antibiotics

Study of Antimicrobial Activity of Alkyl (R-Aryl) Oxy Dialkyl Ammonium Salts Towards the Reference Strains of Microorganisms

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