Yazar "Acar, M. Fahir" seçeneğine göre listele

Listeleniyor 1 - 2 / 2
  • Küçük Resim Yok
    Öğe
    Azole derivatives with naphthalene showing potent antifungal effects against planktonic and biofilm forms ofCandidaspp.: an in vitro and in silico study
    (Springer, 2021) Sari, Suat; Kocak, Ebru; Kart, Didem; Ozdemir, Zeynep; Acar, M. Fahir; Sayoglu, Burcu; Karakurt, Arzu
    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.
  • Küçük Resim Yok
    Öğe
    Azoles containing naphthalene with activity against Gram-positive bacteria: in vitro studies and in silico predictions for flavohemoglobin inhibition
    (Taylor & Francis Inc, 2022) Sari, Suat; Sabuncuoglu, Suna; Aslan, Ebru Kocak; Avci, Ahmet; Kart, Didem; Ozdemir, Zeynep; Acar, M. Fahir
    Azoles are first-line drugs used in fungal infections. Topical antifungals, such as miconazole and econazole, are known to be active against Gram-positive bacteria, which was reported to result from bacterial flavohemoglobin (flavoHb) inhibition. Dual antibacterial/antifungal action is believed to have benefits for antimicrobial chemotherapy. In this study, we tested antibacterial effects of an in-house library of naphthalene-bearing azoles, some of which were reported as potent antifungals, in an attempt to find dual-acting hits. Several potent derivatives were obtained against the Gram-positive bacteria, Enterococcus faecalis and Staphylococcus aureus. 9 was active at a minimum inhibitor concentration (MIC) less than 1 mg/ml against E. faecalis and S. aureus, and 10 against S. aureus. 16 was also potent against E. faecalis and S. aureus (MIC = 1 and 2 mg/ml, respectively). Six more were active against S. aureus with MIC <= 4 mg/ml. In vitro cytotoxicity studies showed that the active compounds were safe for healthy cells within their MIC ranges. According to the calculated descriptors, the library was found within the drug-like chemical space and free of pan-assay interference compounds (PAINS). Molecular docking studies suggested that the compounds might be bacterial flavohemoglobin (flavoHb) inhibitors and the azole and naphthalene rings were important pharmacophores, which was further supported by pharmacophore modeling study. As a result, the current study presents several non-toxic azole derivatives with antibacterial effects. In addition to their previously reported antifungal properties, they could set a promising starting point for the future design of dual acting antimicrobials.