In vitro and in vivo antifungal activities of T-2307, a novel arylamidine, against Cryptococcus gattii: an emerging fungal pathogen

Nishikawa, Hiroshi; Fukuda, Yoshiko; Mitsuyama, Junichi; Tashiro, Masato; Tanaka, Akira; Takazono, Takahiro; Saijo, Tomomi; Yamamoto, Kazuko; Nakamura, Shigeki; Imamura, Yoshifumi; Miyazaki, Taiga; Kakeya, Hiroshi; Yamamoto, Yoshihiro; Yanagihara, Katsunori; Mukae, Hiroshi; Kohno, Shigeru; Izumikawa, Koichi

doi:10.1093/jac/dkx020

Cited by 40 publications

(18 citation statements)

References 19 publications

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“…Interestingly, brain fungal burden was significantly reduced in mice treated with T-2307 at 3 mg/kg (4.16 log 10 CFU/g) and caspofungin (2.51 log 10 CFU/g) versus untreated control (6.31 log 10 CFU/g) (P Յ 0.01). Previous studies have demonstrated reductions in brain and ocular tissue fungal burden in mice infected with Cryptococcus gattii and Candida albicans, respectively, and treated with T-2307 (10,11). In the current study, there was also a clear relationship between fungal burden and survival, as treated mice that survived to the day 21 endpoint had lower kidney and brain fungal burden compared to those that succumbed to infection.…”

supporting

confidence: 66%

The Novel Arylamidine T-2307 Demonstrates In Vitro and In Vivo Activity against Candida auris

Wiederhold

Najvar

Jaramillo

et al. 2020

Antimicrob Agents Chemother

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The in vitro and in vivo activity of the arylamidine T-2307 against Candida auris was evaluated. T-2307 demonstrated in vitro activity (MIC ranges ≤ 0.008 to 0.015 μg/ml at 50% inhibition; 0.125 to >4 μg/ml at 100% inhibition). Treatment with T-2307 (3 mg/kg subcutaneous [SC] once daily) also significantly improved survival (70% at 21 days postinfection) and reduced kidney fungal burden (5.06 log10 CFU/g) compared to control (0% survival and 7.09 log10 CFU/g) (P < 0.01).

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supporting

confidence: 66%

The Novel Arylamidine T-2307 Demonstrates In Vitro and In Vivo Activity against Candida auris

Wiederhold

Najvar

Jaramillo

et al. 2020

Antimicrob Agents Chemother

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“…The efficacy of T-2307 was confirmed in murine models of cryptococcosis: at 0.1 mg/kg, T-2307 significantly delayed mortality in mice infected by C. neoformans when compared with the untreated group, and T-2307 exhibited a superior protective effect compared to AMB at similar treatment regimens [64]. Administration of T-2307 alone at 2 mg/kg/day significantly reduced viable cell counts in the lungs and brain of mice infected by C. gattii and the results were similar to standard treatments [65].…”

Section: T-2307mentioning

confidence: 60%

“…T-2307 is a novel arylamidine derivative with broad-spectrum of action and potent in vitro and in vivo activities, that acts by selectively disrupting mitochondrial function in yeasts [63]. The antifungal activity for C. neoformans was observed at MIC ranging from 0.0039 to 0.0625 µg/mL [64], and for C. gattii at 0.0078-0.0625 µg/mL [65]. The efficacy of T-2307 was confirmed in murine models of cryptococcosis: at 0.1 mg/kg, T-2307 significantly delayed mortality in mice infected by C. neoformans when compared with the untreated group, and T-2307 exhibited a superior protective effect compared to AMB at similar treatment regimens [64].…”

Section: T-2307mentioning

confidence: 99%

New Approaches for Cryptococcosis Treatment

et al. 2020

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Cryptococcosis is an important opportunistic infection and a leading cause of meningitis in patients with HIV infection. The antifungal pharmacological treatment is limited to amphotericin B, fluconazole and 5- flucytosine. In addition to the limited pharmacological options, the high toxicity, increased resistance rate and difficulty of the currently available antifungal molecules to cross the blood–brain barrier hamper the treatment. Thus, the search for new alternatives for the treatment of cryptococcal meningitis is extremely necessary. In this review, we describe the therapeutic strategies currently available, discuss new molecules with antifungal potential in different phases of clinical trials and in advanced pre-clinical phase, and examine drug nanocarriers to improve delivery to the central nervous system.

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“…T2307 is an allylamine that displays significant anticryptococcal activity in vitro and in vivo by collapsing mitochondrial membrane potential. It has very potent anticryptococcal activity against C. gattii in non-immunocompromised murine models of cryptococcosis [ 29 ].…”

Section: Future Therapeutic Options and Directionsmentioning

confidence: 99%

Present and Future Therapy of Cryptococcus Infections

Mourad

Perfect

2018

JoF

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Cryptococcal infections burden the immunocompromised population with unacceptably high morbidity and mortality. This population includes HIV-infected individuals and those undergoing organ transplants, as well as seemingly immunocompetent patients (non-HIV, non-transplant). These groups are difficult to manage with the current therapeutic options and strategies, particularly in resource-limited settings. New trials aimed at providing the best treatment strategies for resource-limited countries that will reduce costs and adverse reactions have focused on decreasing the length of therapy and using more readily accessible antifungal agents such as fluconazole. Furthermore, the emergence of antifungal resistance poses another challenge for successful treatment and may require the development of new agents for improved management. This review will discuss the principles of management, current and future antifungal agents, as well as emerging techniques and future directions of care for this deadly infection.

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In vitro and in vivo antifungal activities of T-2307, a novel arylamidine, against Cryptococcus gattii: an emerging fungal pathogen

Abstract: T-2307 shows excellent in vitro and in vivo antifungal activities against C. gattii and would be a promising new candidate for the treatment of cryptococcosis.

Cited by 40 publications

References 19 publications

The Novel Arylamidine T-2307 Demonstrates In Vitro and In Vivo Activity against Candida auris

The Novel Arylamidine T-2307 Demonstrates In Vitro and In Vivo Activity against Candida auris

New Approaches for Cryptococcosis Treatment

Present and Future Therapy of Cryptococcus Infections

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