Otrescu two , Lucian Mihail Birsa 3 , Laura Gabriela Sarbu three, and Marius Stefan 1, Biology
Otrescu two , Lucian Mihail Birsa three , Laura Gabriela Sarbu three, and Marius Stefan 1, Biology Division, Faculty of Biology, The Alexandru Ioan Cuza University of Iasi, Bld. Carol I, Nr. 11, 700506 Iasi, Romania; [email protected] (C.B.); [email protected] (M.S.) Sciences Division, Research Institute for Agriculture and Atmosphere, Iasi University of Life Sciences, 3 Sadoveanu Alley, 700490 Iasi, Romania; [email protected] Faculty of Chemistry, The Alexandru Ioan Cuza University of Iasi, Bld. Carol I, Nr. 11, 700506 Iasi, Romania; [email protected] Correspondence: [email protected] (L.G.S.); [email protected] (M.S.)Citation: Babii, C.; Savu, M.; Motrescu, I.; Birsa, L.M.; Sarbu, L.G.; Stefan, M. The Antibacterial Synthetic Flavonoid GS-626510 Autophagy BrCl-flav Exhibits Essential Anti-Candida Activity by Damaging Cell Membrane Integrity. Pharmaceuticals 2021, 14, 1130. https://doi.org/10.3390/ph14111130 Academic Editor: Poce Giovanna Received: 9 October 2021 Accepted: three November 2021 Published: six NovemberAbstract: Infections caused by Candida are extremely tough to treat as a Icosabutate Icosabutate Purity & Documentation consequence of increasing antifungal resistance. Current research showed that individuals with Candida infections resistant to fluconazole have quite few treatment possibilities. Therefore, locating new efficient antifungal agents can be a matter of health-related high priority. The aim of this study was to discover the antifungal prospective of BrCl-flav-a representative of a brand new class of synthetic flavonoids with bromine as halogen substituent at the benzopyran core against 4 Candida clinical strains. Determination of minimum inhibitory concentration and minimum fungicidal concentration in addition to the time kill assay indicated a strong antifungal effect of BrClflav against C. albicans, C. parapsilosis, C. krusei and C. glabrata. The investigation of anti-Candida mechanism of action making use of fluorescence microscopy and scanning electron microscopy revealed that Br-Cl flav could inhibit fungal growth by impairing the membrane integrity, the resulting structural damages top to cell lysis. BrCl-flav also showed vital anti-virulence properties against Candida spp., inhibiting biofilm formation and yeast to hyphal transition. A sturdy synergistic antifungal effect against C. albicans strain was observed when BrCl-flav was employed in mixture with fluconazole. BrCl-flav has a very good potential to create new effective antifungal agents in the context of Candida spp. multidrug resistance phenomenon. Search phrases: anti-Candida; synthetic flavonoid; antifungal agents; mechanism of action; synergistic effect1. Introduction Candida pathogenic species are viewed as a significant cause of morbidity and mortality worldwide, representing a serious threat to public health [1]. The most frequently isolated pathogenic species is C. albicans, causing infections which may cause 400 mortality, specially in immunocompromised sufferers [2]. Other species including C. glabrata, C. tropicalis, C. parapsilosis and C. krusei have already been also isolated and are viewed as the main causative agents in 500 of systemic fungal infections [1,3]. Antifungal agents such as azoles, polyenes, echinocandins, nucleoside analogs and allylamines are used to handle Candida infections. Among the available anticandidal agents, fluconazole (a form of azole) is one of the most frequently used drugs for the therapy of Candida infections [4]. Nevertheless, antifungal chemotherapy is challenged by multidrug resistance, phenomenon extensively documented in the literature a.
