Azole derivatives with naphthalene showing potent antifungal effects against planktonic and biofilm forms of Candida spp
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ORIGINAL ARTICLE
Azole derivatives with naphthalene showing potent antifungal effects against planktonic and biofilm forms of Candida spp.: an in vitro and in silico study Suat Sari 1 & Ebru Koçak 1 & Didem Kart 2 & Zeynep Özdemir 3 & M. Fahir Acar 1,4 & Burcu Sayoğlu 1,5 & Arzu Karakurt 3 & Sevim Dalkara 1 Received: 1 April 2020 / Revised: 20 August 2020 / Accepted: 28 August 2020 # Springer Nature Switzerland AG 2020
Abstract Candida infections pose a serious public health threat due to increasing drug resistance. Azoles are first-line antifungal drugs for fungal infections. In this study, we tested an in-house azole collection incorporating naphthalene ring to find hits against planktonic and biofilm forms of resistant Candida spp. In the collection, potent derivatives were identified against the susceptible strains of Candida with minimum inhibitory concentration (MIC) values lower than those of the reference drug, fluconazole. MIC values of 0.125 μg/ml against C. albicans, 0.0625 μg/ml against C. parapsilosis, and 2 μg/ml against C. krusei, an intrinsically azole-resistant non-albicans Candida, were obtained. Some of the derivatives were highly active against fluconazole-resistant clinical isolate of C. tropicalis. Inhibition of C. albicans biofilms was also observed at 4 μg/ml similar as amphotericin B, the reference drug known for its antibiofilm activity. Through molecular docking studies, affinities and key interactions of the compounds with fungal lanosterol 14α-demethylase (CYP51), the target enzyme of azoles, were predicted. The interactions of imidazole with heme cofactor and of the naphthalene with Tyr118 were highlighted in line with the literature data. As a result, this study proves the importance of naphthalene for the antifungal activity of azoles against Candida spp. in both planktonic and biofilm forms. Keywords Naphthalene . Antifungal . Candida . Biofilm . Molecular docking
Introduction Systemic candidiasis is a great public health issue for immunocompromised individuals due to the increased drug resistance among Candida spp. Genus Candidae are prevalent Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10123-020-00144-y) contains supplementary material, which is available to authorized users. * Suat Sari [email protected]; [email protected] 1
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Sihhiye, 06100 Ankara, Turkey
2
Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey
3
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, İnönü University, 44280 Malatya, Turkey
4
Server Gazi Pharmacy, Merkez Efendi, 20040 Denizli, Turkey
5
Tokat State Hospital, 60100 Tokat, Turkey
pathogenic fungi responsible for many types of fungal infections. Although C. albicans is the most commonly identified species in candidiasis, the rise in the cases of infections caused by non-albicans species with natural and acquired drug resistance is of great c
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