89429-62-9Relevant academic research and scientific papers
Synthesis, optimization, antifungal activity, selectivity, and cyp51 binding of new 2-aryl-3-azolyl-1-indolyl-propan-2-ols
Lebouvier, Nicolas,Pagniez, Fabrice,Na, Young Min,Shi, Da,Pinson, Patricia,Marchivie, Mathieu,Guillon, Jean,Hakki, Tarek,Bernhardt, Rita,Yee, Sook Wah,Simons, Claire,Lézé, Marie-Pierre,Hartmann, Rolf W.,Mularoni, Angélique,Le Baut, Guillaume,Krimm, Isabelle,Abagyan, Ruben,Pape, Patrice Le,Borgne, Marc Le
, p. 1 - 32 (2020/08/17)
A series of 2-aryl-3-azolyl-1-indolyl-propan-2-ols was designed as new analogs of fluconazole (FLC) by replacing one of its two triazole moieties by an indole scaffold. Two different chemical approaches were then developed. The first one, in seven steps, involved the synthesis of the key intermediate 1-(1H-benzotriazol-1-yl)methyl-1H-indole and the final opening of oxiranes by imidazole or 1H-1,2,4-triazole. The second route allowed access to the target compounds in only three steps, this time with the ring opening by indole and analogs. Twenty azole derivatives were tested against Candida albicans and other Candida species. The enantiomers of the best anti-Candida compound, 2-(2,4-dichlorophenyl)-3-(1H-indol-1-yl)-1-(1H-1,2,4-triazol-1-yl)-propan-2-ol (8g), were analyzed by X-ray diffraction to determine their absolute configuration. The (?)-8g enantiomer (Minimum inhibitory concentration (MIC) = IC80 = 0.000256 μg/mL on C. albicans CA98001) was found with the S-absolute configuration. In contrast the (+)-8g enantiomer was found with the R-absolute configuration (MIC = 0.023 μg/mL on C. albicans CA98001). By comparison, the MIC value for FLC was determined as 0.020 μg/mL for the same clinical isolate. Additionally, molecular docking calculations and molecular dynamics simulations were carried out using a crystal structure of Candida albicans lanosterol 14α-demethylase (CaCYP51). The (?)-(S)-8g enantiomer aligned with the positioning of posaconazole within both the heme and access channel binding sites, which was consistent with its biological results. All target compounds have been also studied against human fetal lung fibroblast (MRC-5) cells. Finally, the selectivity of four compounds on a panel of human P450-dependent enzymes (CYP19, CYP17, CYP26A1, CYP11B1, and CYP11B2) was investigated.
Novel carbazole-triazole conjugates as DNA-targeting membrane active potentiators against clinical isolated fungi
Zhang, Yuan,Tangadanchu, Vijai Kumar Reddy,Bheemanaboina, Rammohan R. Yadav,Cheng, Yu,Zhou, Cheng-He
, p. 579 - 589 (2018/06/20)
A series of carbazole-triazole conjugates were designed, synthesized and characterized by IR, NMR, and HRMS spectra. Biological assay showed that most of the synthesized compounds exhibited moderate and even strong antifungal activities, especially 3,6-dibromocarbazolyl triazole 5d displayed excellent inhibitory efficacy against most of the tested fungal strains (MIC = 2–32 μg/mL) and effectively fungicidal ability towards C. albicans, C. tropicals and C. parapsilosis ATCC 22019 (MFC = 4–8 μg/mL). Its combination use with fluconazole could enhance the antifungal efficacy, and compound 5d also did not obviously trigger the development of resistance in C. albicans even after 10 passages. Preliminary mechanism study revealed that the active molecule 5d could depolarize fungal membrane potential and intercalate into DNA to possibly block DNA replication, thus possibly exhibiting its powerful antifungal abilities. Conjugate 5d could interact with HSA, which was constructive for the further design, modification and screening of drug molecules. Docking investigation demonstrated a non-covalent binding of 5d with CYP51 through hydrogen bond and hydrophobicity. These results strongly suggested that compound 5d could act as a potential template for the development of promising antifungal drugs.
Design, synthesis, & biological activity of new triazole & nitro-triazole derivatives as antifungal agents
Sadeghpour, Hossein,Khabnadideh, Soghra,Zomorodian, Kamiar,Pakshir, Keyvan,Hoseinpour, Khadijeh,Javid, Nabiollah,Faghih-Mirzaei, Ehsan,Rezaei, Zahra
, (2017/08/26)
In this study two series of fluconazole derivatives bearing nitrotriazole (series A) or piperazine ethanol (series B) side chain were designed and synthesized and then docked in the active site of lanosterol 14α-demethylase enzyme (1EA1) using the Autodock 4.2 program (The scripps research institute, La Jolla, CA, USA). The structures of synthesized compound were confirmed by various methods including elemental and spectral (NMR, CHN, and Mass) analyses. Then antifungal activities of the synthesized compound were tested against several natural and clinical strains of fungi using a broth microdilution assay against several standard and clinical fungi. Nitrotriazole derivatives showed excellent and desirable antifungal activity against most of the tested fungi. Among the synthesized compounds, 5a-d and 5g, possessing nitrotriazole moiety, showed maximum antifungal activity, in particular against several fluconazole-resistant fungi.
Design, synthesis and evaluation of clinafloxacin triazole hybrids as a new type of antibacterial and antifungal agents
Wang, Yan,Damu, Guri L.V.,Lv, Jing-Song,Geng, Rong-Xia,Yang, Da-Cheng,Zhou, Cheng-He
experimental part, p. 5363 - 5366 (2012/09/22)
A series of clinafloxacin triazole hybrids as a new type of antibacterial and antifungal agents were synthesized for the first time and screened for their antimicrobial efficacy against four Gram-positive bacteria, four Gram-negative bacteria and two fungi by two fold serial dilution technique. The bioactive assay indicated that most of the target compounds displayed broad antimicrobial spectrum and good antibacterial and antifungal activities with low MIC values ranging from 0.25 to 2 μg/mL against all the tested strains which exhibited comparable or even better efficiency in comparison with the reference drugs Chloramphenicol, Clinafloxacin and Fluconazole, respectively. Notably, some synthesized clinafloxacin triazoles showed stronger efficacy against methicillin-resistant Staphylococcus aureus than their parent Clinafloxacin.
Efficient microwave-assisted synthesis of 1-(1H-indol-1-yl)-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propan-2-ols as antifungal agents
Lebouvier, Nicolas,Giraud, Francis,Corbin, Typhanie,Na, Young Min,Le Baut, Guillaume,Marchand, Pascal,Le Borgne, Marc
, p. 6479 - 6483 (2007/10/03)
New conazole antifungals, in the series of triazole alcohols 23a-d and 24a-e incorporating an indole moiety substituted at 5-position by halogens, a cyano or 4-methoxyphenyl group, have been synthesized by ring opening of corresponding oxiranes 15 and 16. These dihalogeno intermediates and their congeneers could be prepared in high yields by Corey-Chaykovsky reaction under microwave irradiation.
Synthesis of 1-triazolyl-4-trimethylsilyl-2-butanol and 1-triazolyl-5-trimethylsilyl-2-pentanol derivatives and an investigation of their fungicidal activities
Itoh, Hiroyuki,Yoneda, Rieko,Tobitsuka, Junzo,Ohta, Hiroshi,Takahi, Yukiyoshi,Tsuda, Mikio,Takeshiba, Hideo
, p. 1113 - 1116 (2007/10/03)
A new series of azole derivatives of 1-triazolyl-4-trimethylsilyl-2-butanol and 1-triazolyl-5-trimethylsilyl-2-pentanol were synthesized and evaluated for fungicidal activities against rice blast, sheath blight, and powdery mildew on barley. The derivatives of 2,4-difluorobenzene exhibited high antifungal activities when applied by spray, but exhibited no fungicidal activity by submerged application.
Triazole Derivatives
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, (2008/06/13)
A triazole derivative having antifungal activity is disclosed. The compounds are represented by the following formula: wherein Ar represents a phenyl group or a phenyl group substituted with one or two groups selected from the group consisting of halogen
