Finally, the docking process methodology was first validated by redocking all the co-crystalized original ligands in the active sites of all enzymes with deviation (RMSD) values from 0.86 to 1 1.63 ?. 3.6. Ketoconazole [3,4], itraconazole [3,5], bifonazole [3,6], ravuconazole [3,7], and voriconazole [3,8,9] (Physique 1) are examples of drugs from this class [3]. Since azoles are fungistatic instead of fungicidal, their prolonged use and abuse Methyl β-D-glucopyranoside frequently results in resistance, which is a severe Methyl β-D-glucopyranoside clinical problem in antifungal therapy. The progressive increase in systemic fungal infections over the last three decades has led to high morbidity and mortality rates due to the unavailability of effective medications. The development of resistant strains contributed markedly to this phenomenon. The most aggressive fungal infections occur due to immune suppression associated with several illnesses, such as AIDS, and several drugs which are applied for malignancy chemotherapy, immunosuppressive therapy for organ transplantation, and corticosteroid therapy in inflammatory diseases. More than 90% of reported fungal-associated deaths result from species belonging to three genera: Cryptococcus, Candida, and Aspergillus [10]. Clinically, candidiasis and aspergillosis represent 80% to 90% of systemic fungal infections in immunocompromised patients. Open in a separate windows Physique 1 Determined Rabbit Polyclonal to Cytochrome P450 39A1 pharmaceutically relevant azoles derivatives and 1,2,4-triazoles emphasized by a red color. Considerable use and long-term therapy with azoles resulted in fungal resistance [11,12]. Most of the drugs used in antifungal treatment, except azoles and polyenes, are characterized by low potency, a narrow spectrum of activity, and many severe side effects. These precipitate an urgent need to develop novel effective antifungal azoles with a better clinical efficacy and low risk of side effects. One way to overcome this rapid development of drug resistance is usually to design new agents with chemical characteristics that are different from those of existing brokers. Especially the mechanism of action should be ultimately the same, e.g., Methyl β-D-glucopyranoside different binding sites or different targets are the best possibilities for avoiding cross-resistance to existing therapeutics [13]. Triazole derivatives have attracted considerable interest in the scientific community due to their vast range of biological activities. In addition to antifungal action [14,15,16,17,18,19], they were shown to possess other antimicrobial effects such as antibacterial, including anti-tuberculous activity [20,21,22,23,24], antiparasitic [25,26,27] and anti-HIV effects [28] as well as anticholinesterase [29], antiangiogenic [30], anticancer [31,32], antidiabetic [33,34] and anticonvulsant activities [35]. Another interesting structural core is the chromen ring. Chromen derivatives were also reported to display a wide range of biological activities such as antioxidant [36,37], anti-inflammatory [38,39], antimicrobial [40,41,42,43,44,45], anti-HIV [46,47] and others [48,49]. These findings focused particular interest on incorporating a triazole with a chromen ring in one frame to obtain compounds with improved antifungal activity. According to the current literature, more efficacious antibacterial compounds have been designed by joining two or more biologically active heterocyclic nuclei in a single molecular framework [50,51,52,53]. Taking all these into account, herein we report the design, synthesis, and evaluation of the antifungal activity of fourteen new chromenolCtriazole hybrids. 2. Results and Discussion 2.1. Chemistry The synthesis of new vinyl-1,2,4-triazole derivatives A (Figure 1) as antimicrobial agents was previously reported [54]. Recent attention has only been paid to the tandem reactions of salicylic aldehydes or salicylic imines with ,-unsaturated compounds [55]. We considered that an applicable route to the synthesis of 1370.2/371.1 corresponding to the molecular formula C17H12BrN3O2, which is consistent with the structure assigned to it. The characterization data of compounds 3aCn are given in experimental part. Methyl β-D-glucopyranoside The structure of the compound 3h was characterized by a single-crystal X-ray diffraction method. The compound crystallizes in the centrosymmetric monoclinic space group = 24.207(2), = 9.7963(7), = 14.9130(13) ?, = 100.229(8) and = 3480.2(5) ?3. The structure of the molecule is shown in Figure 3. Methyl β-D-glucopyranoside The nitro group was nearly co-planar to the chromenol fragment and the corresponding dihedral.