Efficacy of SPK-843, a Novel Polyene Antifungal, in Comparison with Amphotericin B, Liposomal Amphotericin B, and Micafungin against Murine Pulmonary Aspergillosis

Kakeya, Hiroshi; Miyazaki, Yoshitsugu; Senda, Hisato; Kobayashi, Tsutomu; Seki, Masafumi; Izumikawa, Koichi; Yanagihara, K.; Yamamoto, Yoshihiro; Tashiro, Takayoshi; Kohno, Shigeru

doi:10.1128/aac.01369-07

Cited by 14 publications

(10 citation statements)

References 10 publications

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“…In general, (PhSe) 2 was the most active compound against Fusarium spp., with a GM-MIC of 5.25 lg ml )1 and a GM-MFC of 14.13 lg ml )1 . In view of the excellent activity of (PhSe) 2 against Fusarium and because of varying susceptibility among Fusarium spp., a molecular analysis was performed to confirm the identity of Fusarium species.…”

Section: Resultsmentioning

confidence: 99%

“…3 Extensive studies have focused on toxicological and pharmacological effects of (PhSe) 2 in different biological models, as reviewed by Nogueira et al [3] and Rosa et al [4], making this compound a good candidate for therapeutic use. Of particular importance, antioxidant, antinociceptive, anti-inflammatory, antisecretory, antiulcer and hepatoprotective properties have been attributed to (PhSe) 2 . 4 As many current antifungal drugs have undesirable side effects and are ineffective against a great number of fungi, there is an urgent need for the next generation of antifungal agents.…”

Section: Discussionmentioning

confidence: 99%

“…The activity of (PhSe) 2 Molecular analysis was performed to confirm the identity of the 28 Fusarium species used. A DNA fragment covering an internal transcribed spacer (ITS) was amplified with primers ITS1 (5¢-TCCGTAGGTGAACCTG-CGG-3¢) and ITS4 (5¢-TCCTCCGCTTATTGATATGC-3¢).…”

Section: Fungal Speciesmentioning

confidence: 99%

“…We attempted to assess the antifungal properties of diphenyl diselenide (PhSe) 2 , an organoselenium (OS) compound with pharmacological and toxicological effects reported in vitro and in animal models. 3,4 The antifungal activity and structure-activity relationships of the synthetic analogues p-chloro-diphenyl diselenide, m-trifluoromethyl-diphenyl diselenide and p-methoxyldiphenyl diselenide were also determined.…”

Section: Introductionmentioning

confidence: 99%

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In vitro antifungal evaluation and structure–activity relationship of diphenyl diselenide and synthetic analogues

Loreto¹,

Mario²,

Santúrio³

et al. 2011

Mycoses

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We report on in vitro antifungal activity and the structure-activity relationship of diphenyl diselenide [(PhSe)(2) ] and its synthetic analogues, (p-Cl-C(6) H(4) Se)(2), (m-CF(3)-C(6) H(4)Se)(2) and (p-CH(3)O-C(6) H(4)Se)(2), against 116 strains of pathogenic fungi. (PhSe)(2) showed the highest inhibitory activity against Candida albicans (minimum inhibitory concentration of 4-32 μg ml(-1) ), Candida dubliniensis (2-16 μg ml(-1)), Aspergillus spp. (0.5-64 μg ml(-1)) and Fusarium spp. (2-16 μg ml(-1)). Its minimum fungicidal concentration (MFC) varied among C. albicans (4-64 μg ml(-1)), C. dubliniensis (2-32 μg ml(-1) ) and Fusarium spp. (4-64 μg ml(-1)). Antifungal activity was decreased by the introduction of functional groups to the (PhSe)(2) molecule: (PhSe)(2) >(p-CH(3)O-C(6)H(4) Se)(2) >(m-CF(3)-C(6)H(4)Se)(2) >(p-Cl-C(6) H(4)Se)(2).

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Fungal Speciesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

In vitro antifungal evaluation and structure–activity relationship of diphenyl diselenide and synthetic analogues

Loreto¹,

Mario²,

Santúrio³

et al. 2011

Mycoses

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“…Mice were immunosuppressed as previously described [12,13]. The L-AMB solution was aerosolized using a nebulizer (Muromachi Kikai Co., Ltd., Tokyo, Japan), and mice were exposed to aerosol treatment for 60 min as previously described [9].…”

Section: Immunosuppressionmentioning

confidence: 99%

Efficacy of aerosolized liposomal amphotericin B against murine invasive pulmonary mucormycosis

Mihara

Kakeya

Izumikawa

et al. 2014

Journal of Infection and Chemotherapy

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Invasive pulmonary mucormycosis is a life-threatening fungal infection encountered in immunocompromised patients. An intravenous high-dose lipid formulation of amphotericin B, such as liposomal amphotericin B (L-AMB), is the recommended treatment. The efficacy of inhaled L-AMB against mucormycosis has not been evaluated.We evaluated the efficacy of inhaled aerosolized L-AMB in murine invasive pulmonary mucormycosis. ICR female mice were immunosuppressed with cortisone acetate and cyclophosphamide and challenged on day 0 with 1 × 10 6 conidia of Rhizopus oryzae (TIMM 1327) intratracheally. Infected mice were assigned to one of the following 3 treatment groups: (i) control, (ii) treatment only (aerosolized L-AMB from day 1-5 after challenge), and (iii) prophylaxis followed by treatment (aerosolized L-AMB from day -2-5 before and after challenge). Survival was monitored until 12 days after challenge.For fungal-burden and histopathological examination, mice were sacrificed 4 h after treatment on day 3. Numbers of colony-forming units per lung were calculated. To study the distribution of AMB after inhalation of L-AMB, immunohistochemical studies using AMB antibody were performed.Aerosolized L-AMB significantly improved survival rate and decreased fungal burden compared with control group, and histopathology findings were superior to those of control group. However, no significant differences were detected between the treatment-only and prophylaxis followed by treatment groups. Immunohistochemical analysis showed that L-AMB was promptly distributed in lung tissue after inhalation therapy. 3Aerosolized L-AMB showed modest efficacy against R. oryzae infection in mice treated after fungal challenge. Prophylaxis with aerosolized L-AMB was not effective in this animal model.

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Antifungals: Mechanism of Action and Drug Resistance

Prasad

Shah

Rawal

2016

Advances in Experimental Medicine and Biology

153

104

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There are currently few antifungals in use which show efficacy against fungal diseases. These antifungals mostly target specific components of fungal plasma membrane or its biosynthetic pathways. However, more recent class of antifungals in use is echinocandins which target the fungal cell wall components. The availability of mostly fungistatic antifungals in clinical use, often led to the development of tolerance to these very drugs by the pathogenic fungal species. Thus, the development of clinical multidrug resistance (MDR) leads to higher tolerance to drugs and its emergence is helped by multiple mechanisms. MDR is indeed a multifactorial phenomenon wherein a resistant organism possesses several mechanisms which contribute to display reduced susceptibility to not only single drug in use but also show collateral resistance to several drugs. Considering the limited availability of antifungals in use and the emergence of MDR in fungal infections, there is a continuous need for the development of novel broad spectrum antifungal drugs with better efficacy. Here, we briefly present an overview of the current understanding of the antifungal drugs in use, their mechanism of action and the emerging possible novel antifungal drugs with great promise.

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Efficacy of SPK-843, a Novel Polyene Antifungal, in Comparison with Amphotericin B, Liposomal Amphotericin B, and Micafungin against Murine Pulmonary Aspergillosis

Cited by 14 publications

References 10 publications

In vitro antifungal evaluation and structure–activity relationship of diphenyl diselenide and synthetic analogues

In vitro antifungal evaluation and structure–activity relationship of diphenyl diselenide and synthetic analogues

Efficacy of aerosolized liposomal amphotericin B against murine invasive pulmonary mucormycosis

Antifungals: Mechanism of Action and Drug Resistance

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