4252-78-2Relevant articles and documents
Chalcone-Benzotriazole Conjugates as New Potential Antimicrobial Agents: Design, Synthesis, Biological Evaluation and Synergism with Clinical Drugs
Liu, Hanbo,Gopala, Lavanya,Avula, Srinivasa Rao,Jeyakkumar, Ponmani,Peng, Xinmei,Zhou, Chenghe,Geng, Rongxia
, p. 483 - 496 (2017)
A series of chalcone-benzotriazole conjugates as new potential antimicrobial agents were synthesized and characterized by 1H NMR, 13C NMR, IR and HRMS spectra. Antimicrobial assay manifested that some target compounds gave moderate to good antibacterial and antifungal activities. The N-1 derived benzotriazole 5e and N-2 derived benzotriazole 6a exhibited valuable inhibitory efficacy against some tested strains. Especially, derivative 6a gave superior antifungal efficacies against C. utilis, S. cerevisiae and A. flavus (MIC=0.01, 0.02, 0.02 μmol/mL, respectively) to Fluconazole. The drug combination of compound 5e or 6a with antibacterial Chloromycin, Norfloxacin and antifungal Fluconazole respectively showed stronger antimicrobial efficiency with less dosage and broader antimicrobial spectrum than their separated use alone. The preliminary interaction with calf thymus DNA revealed that compound 6a could intercalate into DNA to form 6a-DNA supramolecular complex which might be a factor to exert its powerful bioactivity. Molecular docking study indicated strong binding of compound 6a with DNA gyrase. The structural parameters such as molecular orbital energy and molecular electrostatic potential of compound 6a were also investigated, which provided better understanding for its good antimicrobial activity.
Lead optimization generates selenium-containing miconazole CYP51 inhibitors with improved pharmacological profile for the treatment of fungal infections
Xu, Hang,Yan, Zhong-zuo,Guo, Meng-bi,An, Ran,Wang, Xin,Zhang, Rui,Mou, Yan-hua,Hou, Zhuang,Guo, Chun
, (2021/03/16)
A series of selenium-containing miconazole derivatives were identified as potent antifungal drugs in our previous study. Representative compound A03 (MIC = 0.01 μg/mL against C.alb. 5314) proved efficacious in inhibiting the growth of fungal pathogens. However, further study showed lead compound A03 exhibited potential hemolysis, significant cytotoxic effect and unfavorable metabolic stability and was therefore modified to overcome these drawbacks. In this article, the further optimization of selenium-containing miconazole derivatives resulted in the discovery of similarly potent compound B17 (MIC = 0.02 μg/mL against C.alb. 5314), exhibiting a superior pharmacological profile with decreased rate of metabolism, cytotoxic effect and hemolysis. Furthermore, compound B17 showed fungicidal activity against Candida albicans and significant effects on the treatment of resistant Candida albicans infections. Meanwhile, compound B17 not only could reduce the ergosterol biosynthesis pathway by inhibiting CYP51, but also inhibited biofilm formation. More importantly, compound B17 also shows promising in vivo efficacy after intraperitoneal injection and the PK study of compound B17 was evaluated. In addition, molecular docking studies provide a model for the interaction between the compound B17 and the CYP51 protein. Overall, we believe that these selenium-containing miconazole compounds can be further developed for the potential treatment of fungal infections.
Design, synthesis, and biological evaluation of novel miconazole analogues containing selenium as potent antifungal agents
An, Ran,Guo, Chun,Guo, Meng-bi,Hou, Zhuang,Mou, Yan-hua,Su, Xin,Xu, Hang
, (2020/05/11)
Herein, based on the theory of bioisosterism, a series of novel miconazole analogues containing selenium were designed, synthesized and their inhibitory effects on thirteen strains of pathogenic fungi were evaluated. It is especially encouraging that all the novel target compounds displayed significant antifungal activities against all tested strains. Furthermore, all the target compounds showed excellent inhibitory effects on fluconazole-resistant fungi. Subsequently, preliminary mechanistic studies indicated that the representative compound A03 had a strong inhibitory effect on C.alb. CYP51. Moreover, the target compounds could prevent the formation of fungi biofilms. Further hemolysis test verified that potential compounds had higher safety than miconazole. In addition, molecular docking study provided the interaction modes between the target compounds and C.alb. CYP51. These results strongly suggested that some target compounds are promising as novel antifungal drugs.
Novel triazole derivatives containing different ester skeleton: Design, synthesis, biological evaluation and molecular docking
Han, Xiaoyan,Ren, Liwen,Song, Yali,Sun, Xiaoyang,Wang, Jinhua,Wang, Shumin,Xiao, Bin,Zhang, Na
, p. 64 - 69 (2020/02/03)
Invasive fungal disease constitutes a growing health problem and development of novel antifungal drugs with high potency and selectivity are in an urgent need. In this study, a novel series of triazole derivatives containing different ester skeleton were designed and synthesized. Microdilution broth method was used to investigate antifungal activity. Significant inhibitory activity of compounds 5c, 5d, 5e, 5f, 5m and 5n was evaluated against the Candida albicans (I), Candida albicans clinical isolate (II), Candida glabrata clinical isolate (I), and Candida glabrata (II) with minimum inhibitory concentrations (MIC80) values ranging from 2 to 16μg/mL. Notably, compounds 5e and 5n showed the best inhibition against Candida albicans (II), Candida glabrata (I), and Candida glabrata (II) at the concentrations of 2 and 8μg/mL, respectively. Molecular docking study revealed that the target compounds interacted with CYP51 mainly through hydrophobic and van der Waals interactions. The results indicated that these novel triazole derivatives could serve as promising leads for development of antifungal agents.
A new exploration towards aminothiazolquinolone oximes as potentially multi-targeting antibacterial agents: Design, synthesis and evaluation acting on microbes, DNA, HSA and topoisomerase IV
Wang, Liang-Liang,Battini, Narsaiah,Bheemanaboina, Rammohan R. Yadav,Ansari, Mohammad Fawad,Chen, Jin-Ping,Xie, Yun-Peng,Cai, Gui-Xin,Zhang, Shao-Lin,Zhou, Cheng-He
, p. 166 - 181 (2019/07/02)
This work did a new exploration towards aminothiazolquinolone oximes as potentially multi-targeting antimicrobial agents. A class of novel hybrids of quinolone, aminothiazole, piperazine and oxime fragments were designed for the first time, conveniently synthesized as well as characterized by 1H NMR, 13C NMR and HRMS spectra. Biological activity showed that some of the synthesized compounds exhibited good antimicrobial activities in comparison with the reference drugs. Especially, O-methyl oxime derivative 10b displayed excellent inhibitory efficacy against MRSA and S. aureus 25923 with MIC values of 0.009 and 0.017 mM, respectively. Further studies indicated that the highly active compound 10b showed low toxicity toward BEAS-2B and A549 cell lines and no obvious propensity to trigger the development of bacterial resistance. Quantum chemical studies have also been conducted and rationally explained the structural features essential for activity. The preliminarily mechanism exploration revealed that compound 10b could not only exert efficient membrane permeability by interfering with the integrity of cells, bind with topoisomerase IV–DNA complex through hydrogen bonds and π-π stacking, but also form a steady biosupramolecular complex by intercalating into DNA to exert the efficient antibacterial activity. The supramolecular interaction between compound 10b and human serum albumin (HSA) was a static quenching, and the binding process was spontaneous, where hydrogen bonds and van der Waals force played vital roles in the supramolecular transportation of the active compound 10b by HSA.
Method for synthesizing azaconazole through 4-amino-4H-1,2,4-triazole alkylation
-
, (2018/11/03)
The invention discloses a method for synthesizing azaconazole through 4-amino-4H-1,2,4-triazole alkylation. The method comprises step 1, preparing a raw material which is shown in a following image; step 2, synthesizing 1-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazole-1-yl) ethanone; step 3, synthesizing azaconazole. The method disclosed by the invention has the advantages that development of a novel azaconazole bactericide successfully fills the blank in China, synthesis researches of similar derivatives based on the azaconazole bactericide will be in the ascendant, and successful development andindustrial implementation of varieties of novel bactericides have a far-reaching influence on national economy development. The method disclosed by the invention is an azaconazole synthesizing method.
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.
Synthesis and evaluation of novel benzene-ethanol bearing 1,2,4-triazole derivatives as potential antimicrobial agents
Li, Bochao,Zhang, Dawei,Zhang, Yumin,Dan Jiang,Li, Shuang,Lei, Wei,Wang, Huiying,Lin, Feng
, p. 44 - 51 (2017/01/12)
The azole pharmacophore is still regarded as a viable lead structure for the synthesis of more efficacious and broad-spectrum antimicrobial agents. In this study, a novel series of triazole derivates that are structurally related to the famous antimicrobial azole pharmacophore were synthesized and the structures of them were characterized by spectral (IR, 1H NMR, 13C NMR, and MS spectra) analysis. Antimicrobial activity was measured against both bacteria and fungus. In vitro antimicrobial evaluation showed that five compounds had growth inhibitory effects on the tested Gram-positive bacteria and fungus with special efficacy. Potential antibacterial and antifungal activities are incorporated in these triazole compounds. Results of antimicrobial activities also revealed that compounds (5a–i) were the potent antibacterial and antifungal agents as compared to standard drugs (ciprofloxacin and itraconazole), and thus could be promising new lead molecules.
Method for synthesizing Luliconazole
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Paragraph 0003; 0007, (2016/10/09)
The invention relates to a method for synthesizing Luliconazole. The method comprises the steps of subjecting m-dichlorobenzene to Friedel-Crafts acylation with chloroacetyl chloride, catalytic chiral reduction with (S)-2-methyl-CBS-oxazaborolidine and esterification with methylsulfonyl chloride so as to obtain (S)-2,2',4'-ethyl trichlorobenzene methanesulfonate, and finally, subjecting (S)-2,2',4'-ethyl trichlorobenzene methanesulfonate to a reaction with carbon disulfide and imidazolyl acetonitrile, thereby obtaining Luliconazole. According to the method, the total yield is about 30%.
PROCESS FOR PREPARATION OF LULICONAZOLE
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Paragraph 0120, (2016/11/07)
A process for the preparation of luliconazole and salts thereof is disclosed.
