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Asarones from Acorus calamus in Combination with Azoles and Amphotericin B: A Novel Synergistic Combination to Compete Against Human Pathogenic Candida Species In Vitro

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Abstract

The increase in drug resistance to current antifungal drugs brings enormous challenges to the management of Candida infection. Therefore, there is a continuous need for the discovery of new antimicrobial agents that are effective against Candida infections especially from natural source especially from medical plants. The present investigation describes the synergistic anticandidal activity of two asarones (∞ and β) purified from Acorus calamus in combination with three clinically used antifungal drugs (fluconazole, clotrimazole, and amphotericin B). The synergistic anticandidal activities of asarones and drugs were assessed using the checkerboard microdilution and time-kill assays. The results of the present study showed that the combined effects of asarones and drugs principally recorded substantial synergistic activity (fractional inhibitory concentration index (FICI) <0.5). Time-kill study by combination of the minimal inhibitory concentration (MIC) of asarones and drugs (1:1) recorded that the growth of the Candida species was significantly arrested between 0 and 2 h and almost completely attenuated between 2 and 6 h of treatment. These findings have potential implications in adjourning the development of resistance as the anticandidal activity is achieved with lower concentrations of asarones and drugs. The combination of asarones and drugs also significantly inhibit the biofilm formation by Candida species, and this would also help to fight against drug resistance because biofilms formed by Candida species are ubiquitous in nature and are characterized by their recalcitrance toward antimicrobial treatment. The in vitro synergistic activity of asarones and drugs against pathogenic Candida species is reported here for the first time.

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Acknowledgments

The authors are thankful to Director, NIIST and Kerala State Council for Science, Technology and Environment (KSCSTE), Govt. of Kerala for providing the necessary facility and fund to carry out the present work. Acknowledgment to DST for providing INSPIRE fellowship to Jubi Jacob (IF 130648).

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The authors declare that they have no conflicts of interest.

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    Authors and Affiliations

    1. Agroprocessing and Natural Products Division, National Institute for Interdisciplinary Science and Technology (NIIST), Council of Scientific and Industrial Research (CSIR), Thiruvananthapuram, Kerala, 695 019, India

      S. Nishanth Kumar, Jubi Jacob & B. S. Dileep Kumar

    2. Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, Kerala, 695011, India

      S. R. Aravind & T. T. Sreelekha

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    1. S. Nishanth Kumar
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    2. S. R. Aravind
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    3. T. T. Sreelekha
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    5. B. S. Dileep Kumar
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    Correspondence to S. Nishanth Kumar or B. S. Dileep Kumar.

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    S. Nishanth Kumar and S. R. Aravind contributed equally to this work.

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    Kumar, S.N., Aravind, S.R., Sreelekha, T.T. et al. Asarones from Acorus calamus in Combination with Azoles and Amphotericin B: A Novel Synergistic Combination to Compete Against Human Pathogenic Candida Species In Vitro. Appl Biochem Biotechnol 175, 3683–3695 (2015). https://doi.org/10.1007/s12010-015-1537-y

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