Novel tetralin compounds were designed and synthesized on the three-dimensional model of lanosterol 14α-demethylase of Candida albicans. All of the lead compounds exhibited potent antifungal activities, especially co...Novel tetralin compounds were designed and synthesized on the three-dimensional model of lanosterol 14α-demethylase of Candida albicans. All of the lead compounds exhibited potent antifungal activities, especially compounds 16, 20. The mode of the action of the lead compounds was different from that of azoles. The present study affords the possibility to develop novel antifungal agents that specifically interact with the amino acid residues in the active site and avoid the serious toxicity arising from coordination binding with the heme of mammalian P450s.展开更多
Novel chiral tetralin compounds were designed and synthesized, and their antifungal activities in vitro were tested. The results showed that all of target compounds had potent antifungal activities, and were stronger ...Novel chiral tetralin compounds were designed and synthesized, and their antifungal activities in vitro were tested. The results showed that all of target compounds had potent antifungal activities, and were stronger than that of control compounds tetrahydroisoquinolines. The binding model of lead molecules in the active site of CYP51 of Candida albicans showed that lead compound specifically interacted with the amino acids residues in the active site, without binding with the heme of CYP51, which was different from azole antifungal drugs. The present study might afford a novel lead molecule to develop non-azole CYP51 inhihitars of fungi.展开更多
Based on the active site of Candida albicans lanosterol 14α-demethylase (CACYP51), novel triazole compounds structurally different from the current triazole drugs were designed and synthesized. In vitro antifungal ac...Based on the active site of Candida albicans lanosterol 14α-demethylase (CACYP51), novel triazole compounds structurally different from the current triazole drugs were designed and synthesized. In vitro antifungal activities showed that compounds 10, 11, 16 and 20 exhibited strong activities. In addition, compounds 10, 11 and 16 also displayed certain activities against fluconazole-resistant fungi.展开更多
基金supported by the National Natural Science Foundation of China(No.30572257)
文摘Novel tetralin compounds were designed and synthesized on the three-dimensional model of lanosterol 14α-demethylase of Candida albicans. All of the lead compounds exhibited potent antifungal activities, especially compounds 16, 20. The mode of the action of the lead compounds was different from that of azoles. The present study affords the possibility to develop novel antifungal agents that specifically interact with the amino acid residues in the active site and avoid the serious toxicity arising from coordination binding with the heme of mammalian P450s.
文摘Novel chiral tetralin compounds were designed and synthesized, and their antifungal activities in vitro were tested. The results showed that all of target compounds had potent antifungal activities, and were stronger than that of control compounds tetrahydroisoquinolines. The binding model of lead molecules in the active site of CYP51 of Candida albicans showed that lead compound specifically interacted with the amino acids residues in the active site, without binding with the heme of CYP51, which was different from azole antifungal drugs. The present study might afford a novel lead molecule to develop non-azole CYP51 inhihitars of fungi.
文摘Based on the active site of Candida albicans lanosterol 14α-demethylase (CACYP51), novel triazole compounds structurally different from the current triazole drugs were designed and synthesized. In vitro antifungal activities showed that compounds 10, 11, 16 and 20 exhibited strong activities. In addition, compounds 10, 11 and 16 also displayed certain activities against fluconazole-resistant fungi.
