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    • androgen receptor inhibitor Agglutinin like sequence ALS gen

    2019-07-16

    Agglutinin-like sequence (ALS) gene is well-characterized gene family in candidiasis due to its importance in pathogenicity of C albicans. Previously, C. albicans ALS1 gene product was reported as cell surface protein that mediates adherence to endothelial and epithelial androgen receptor inhibitor in vitro and during bio-film development (Fu et al., 2002). Evaluation of C. albicans ALS proteins in human oral epithelial cell interactions was previously detected (Fu et al., 2002, Hoyer et al., 2008). Moreover, previous correlation between C. albicans and COX-2 was also investigated (Athikomkulchai et al., 2006). Regarding high cost associated with mucosal candidiasis and emerging resistance of Candida spp. to available antifungal agents that limit therapeutic options novel antifungal approaches have attracted the interest of many researchers in this field (Marchaim et al., 2012) Recently, two novel compounds 2-(4-(Pyridin-2-yl) aminosulfonylphenylamino)-6-(naphthalen-2-yl)-4-(pyridin-2-yl) pyridine-3 carbonitrile and 2-(4-(Pyrimidin-2-yl) aminosulfonylphenylamino)-6-(naphthalen-2-yl)-4-(pyridine-2-yl) pyridine-3-carbonitrile (13b & 14b respectively) were synthesized (Kotb et al., 2015). These compounds have been characterized and demonstrated antimicrobial evaluation in vitro, especially against C. albicans (Kotb et al., 2015). The main aim of the current study is to investigate more efficient and less toxic synthetic compounds for C. albicans treatment via two target new synthesized compounds (13b & 14b) were estimated as anti-fungal agents in vivo.
    Material and methods
    Results
    Discussion Although fluconazole is the most commonly used drug for C. albicans treatment, lots of problems were associated with fluconazole administration as resistance and accumulation in the body that influence several inflammation reactions along with affecting function of different organs (Elizabeth and Shawn, 2017, Popp et al., 2017). Previously, some studies elucidated the ability of triazoles to induce hepatic cytochromes (Cyps) which play a vital role in the metabolism of azole drugs in the liver (Somchit et al., 2004, Sun et al., 2006). Different available antimicrobial drugs are composed of naphthalene nucleus such as naacillin, naftifine, tolnaftate and terbinafine (Rokade and Sayyed, 2009). These antifungal drugs are used for treatment of tinea pedis, tinea cruris and tinea corporis (Desai et al., 2012). It affects bactericidal activity via inhibition of bacterial cell wall synthesis by binding one or more of the penicillin binding proteins (PBPs) (Overington et al., 2006). Previously, pyridine was reported as antimicrobial agent. It inhibits folate synthesis which is responsible for DNA and RNA synthesis in bacteria. So it inhibits cell division. Furthermore it is a competitive inhibitor of the bacterial enzyme dihydropteroate synthase (Imming et al., 2006, McDonald et al., 2009). In the present study, assessment of the efficiency of the new synthetic compounds (13b and 14b) that are formed of a combination of both naphthalene and pyridine moieties in order to overcome the resistant problems associated with traditional antifungal drugs in marketing is carried out. The current study revealed that C. albicans infection elevated serum ALT and AST activities as well as butyrylcholinesterase as compared to the control value. Increased liver enzymes were pointed to cellular leakage indicating liver damage. It has been previously demonstrated that numerous liver function tests were altered post C. albicans infection (Minemura et al., 2014). In addition to hepatic MDA elevation indicating oxidative stress induced by C. albicans. Treatment with fluconazole exhibited a significant increment in ALT liver marker as compared to candida group specialy in high dose. This elevation suggested hepatic toxicity of fluconazole (Khoza et al., 2017). On the other hand, treatment with 13b and 14b exhibited a significant reduction in ALT as compared to Candida group. This reduction reflected the hepato-protective effect of these agents.