22793-16-4Relevant academic research and scientific papers
Design, synthesis and biological evaluation of novel semicarbazone-selenochroman-4-ones hybrids as potent antifungal agents
Xu, Hang,Su, Xin,Liu, Xiao-qian,Zhang, Kai-peng,Hou, Zhuang,Guo, Chun
, (2019/10/19)
A series of novel 2,3-dihydro-4H-1-benzoselenin-4-one (thio)semicarbazone derivatives were designed and synthesized by using molecular hybridization approach. All the target compounds were characterized by HRMS and NMR and evaluated in vitro antifungal activity against five pathogenic strains. In comparison with precursor selenochroman-4-ones, the hybrid molecules in this study showed significant improvement in antifungal activities. Notably, compound B8 showed significant antifungal activity against other strains excluding Aspergillus fumigatus (0.25 μg/mL on Candida albicans, 2 μg/mL on Cryptococcus neoformans, 8 μg/mL on Candida zeylanoides and 2 μg/mL on fluconazole-sensitive strains of Candida albicans). Moreover, compounds B8, B9 and C2 also displayed most potent activities against four fluconazole-resistance strains. Especially the MIC values of the hybrid molecule B8 against fluconazole-resistant strains were in the range of 0.5–2 μg/mL. Therefore, the molecular hybridization approach in this study provided new ideas for the development of antifungal drug.
Design, Synthesis and Antifungal Activity of Benzofuran and Its Analogues
Xu, Hang,Hou, Zhuang,Liang, Zhen,Guo, Meng-Bi,Su, Xin,Guo, Chun
, p. 1245 - 1250 (2019/11/21)
Benzofuran has antifungal activity as the inhibitor of N-myristoyltransferase. Twenty-nine novel benzofuran-semicarbazide hybrids were designed and synthesized by principle of drug combinationatory. On this basis, the benzofuran ring was simplified to a resorcinol structure, and sixteen novel 1,3-dialkoxybenzene-semicarbazide hybrids were designed and synthesized. All structures of the target compounds were characterized by HRMS and NMR. The in vitro antifungal activity of target compounds was evaluated using the microdilution broth method against eight strains of pathogenic fungi with fluconazole as positive control. According to the results of the target compounds, structure-activity relationship (SAR) is summarized. The inhibitory activity against the tested strains of simplified compounds (K01—K16) has different levels improvement compared with compounds Z01—Z29. K01—K16 showed significant antifungal activities against A. fumigatus, C. kruseii, and sensitive C. albicans 5314. Notably, compounds Z20, Z22, K10, K11 and K16 also displayed different activities against two fluconazole-resistance strains that were isolated from AIDS patients. The minimal inhibitory concentration (MIC) values against fluconazole-resistant strains were in the range of 2—8 μg/mL and 4—32μg/mL, respectively. Furthermore, molecular docking was performed to investigate the binding affinities and interaction modes between the target compound and N-myristoyltransferase.
Synthesis and antimalarial activity of novel dihydro-artemisinin derivatives
Liu, Yang,Cui, Kunqiang,Lu, Weiqiang,Luo, Wei,Wang, Jian,Huang, Jin,Guo, Chun
, p. 4527 - 4538 (2011/08/10)
The Plasmodium falciparum cysteine protease falcipain-2, one of the most promising targets for antimalarial drug design, plays a key role in parasite survival as a major peptide hydrolase within the hemoglobin degradation pathway. In this work, a series of novel dihydroartemisinin derivatives based on (thio)semicarbazone scaffold were designed and synthesized as potential falcipain-2 inhibitors. The in vitro biological assay indicated that most of the target compounds showed excellent inhibition activity against P. falciparum falcipain-2, with IC50 values in the 0.29-10.63 μM range. Molecular docking studies were performed to investigate the binding affinities and interaction modes for the inhibitors. The preliminary SARs were summarized and could serve as a foundation for further investigation in the development of antimalarial drugs.
Design and synthesis of novel triazole antifungal derivatives by structure-based bioisosterism
Sheng, Chunquan,Che, Xiaoying,Wang, Wenya,Wang, Shengzheng,Cao, Yongbing,Miao, Zhenyuan,Yao, Jianzhong,Zhang, Wannian
, p. 5276 - 5282 (2011/12/03)
The incidence of life-threatening fungal infections is increasing dramatically. In an attempt to develop novel antifungal agents, our previously synthesized phenoxyalkylpiperazine triazole derivatives were used as lead structures for further optimization. By means of structure-based bioisosterism, triazolone was used as a new bioisostere of oxygen atom. This type of bioisosteric replacement can improve the water solubility without loss of hydrogen-bonding interaction with the target enzyme. A series of triazolone-containing triazoles were rationally designed and synthesized. As compared with fluconazole, several compounds showed higher antifungal activity with broader spectrum, suggesting their potential for further evaluations.
