Azole derivatives with naphthalene showing potent antifungal effects against planktonic and biofilm forms ofCandidaspp.: an in vitro and in silico study

SARI S., Kocak E., KART D., ÖZDEMİR Z., Acar M. F., Sayoglu B., ...Daha Fazla

INTERNATIONAL MICROBIOLOGY, cilt.24, sa.1, ss.93-102, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 24 Sayı: 1
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1007/s10123-020-00144-y
  • Dergi Adı: INTERNATIONAL MICROBIOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Agricultural & Environmental Science Database, BIOSIS, CAB Abstracts, EMBASE, Environment Index, Food Science & Technology Abstracts, MEDLINE, Pollution Abstracts, Veterinary Science Database, DIALNET
  • Sayfa Sayıları: ss.93-102
  • Anahtar Kelimeler: Naphthalene, Antifungal, Candida, Biofilm, Molecular docking, OXIME ETHER DERIVATIVES, ACCURATE DOCKING, ANTICONVULSANT, SUSCEPTIBILITY, PROTEIN, GLIDE, MODEL
  • İnönü Üniversitesi Adresli: Evet

Özet

Candidainfections 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 resistantCandidaspp. In the collection, potent derivatives were identified against the susceptible strains ofCandidawith minimum inhibitory concentration (MIC) values lower than those of the reference drug, fluconazole. MIC values of 0.125 mu g/ml againstC. albicans, 0.0625 mu g/ml againstC. parapsilosis, and 2 mu g/ml againstC. krusei, an intrinsically azole-resistant non-albicans Candida, were obtained. Some of the derivatives were highly active against fluconazole-resistant clinical isolate ofC. tropicalis. Inhibition ofC. albicansbiofilms was also observed at 4 mu g/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 14 alpha-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 againstCandidaspp. in both planktonic and biofilm forms.