32-hydroxylanosterol | 111420-56-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 32-hydroxylanosterol
• 英文别名: (3S,5R,10S,13R,14S,17R)-14-(hydroxymethyl)-4,4,10,13-tetramethyl-17-[(2R)-6-methylhept-5-en-2-yl]-2,3,5,6,7,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-ol
• CAS: 111420-56-5
• 化学式: C₃₀H₅₀O₂
• 分子量: 442.726
• InChiKey: DWVYYKFZEDMMPU-PUXRVUTHSA-N

物化性质

• 沸点：
  535.0±50.0 °C(Predicted)
• 密度：
  1.03±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  羊毛甾醇 在 recombinant rat NADPH-P₄₅₀ reductase 、 C-terminal His₆-tagged Candida albicans CYP₅₁F₁ 、 1,2-二亚油酰基-sn-甘油-3-磷酸胆碱 作用下， 反应 0.5h， 生成 32-hydroxylanosterol 、 (3R,5S,10S,13S,17S)-4,4,10,13-四甲基-17-[(2R)-6-甲基庚-5-烯-2-基]-1,2,3,5,6,7,11,12,16,17-十氢环戊烯并[a]菲-3-醇
  参考文献：
  名称：

  Heterologous expression and characterization of the sterol 14α-demethylase CYP51F1 from Candida albicans

  摘要：

  Lanosterol 14 alpha-demethylase (CYP51F1) from Candida albicans is known to be an essential enzyme in fungal sterol biosynthesis. Wild-type CYP51F1 and several of its mutants were heterologously expressed in Escherichia coli, purified, and characterized. It exhibited a typical reduced CO-difference spectrum with a maximum at 446 nm. Reconstitution of CYP51F1 with NADPH-P450 reductase gave a system that successfully converted lanosterol to its demethylated product. Titration of the purified enzyme with lanosterol produced a typical type I spectral change with K-d = 6.7 mu M. The azole antifungal agents econazole, fluconazole, ketoconazole, and itraconazole bound tightly to CYP51F1 with K-d values between 0.06 and 0.42 mu M. The CYP51F1 mutations F105L, D116E, Y132H, and R467K frequently identified in clinical isolates were examined to determine their effect on azole drug binding affinity. The azole K-d values of the purified F105L, D116E, and R467K mutants were little altered. A homology model of C. albicans CYP51F1 suggested that Tyr132 in the BC loop is located close to the heme in the active site, providing a rationale for the modified heme environment caused by the Y132H substitution. Taken together, functional expression and characterization of CYP51F1 provide a starting basis for the design of agents effective against C. albicans infections. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.abb.2011.02.002

文献信息

• Compounds and methods for the inhibition of compounds cruzi
  申请人：Hamilton D Andrew

  公开号：US20060167269A1

  公开（公告）日：2006-07-27

  The present invention relates to compounds according to the formula (I): Where R A is a C 1 -C 10 substituted or unsubstituted linear, branch-chained or cyclic alkyl or alkenyl group or a phenyl group according to the formula (II): R B is a C 1 -C 10 substituted or unsubstituted linear, branch-chained or cyclic alkyl or alkenyl group or a phenyl group of the formula (III): R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 are each independently selected from H, C 1 -C 10 (preferably a C 1 -C 4 ) alkyl or alkenyl group, CF 3 , F, Cl, Br, I, CN, NO 2 , NH 2 , NHR, NRR, COR (acyl group), OR (hydroxyl or ether group), CO 2 R (carboxylic acid or ester group), or COSR (thioester group) where R is H or a C 1 -C 10 (preferably a C 1 -C 4 ) alkyl or alkenyl group, an unsubstituted or substituted aryl (preferably, phenyl) or heterocycle group, or a (IV) group, where R 3 is H, a C 1 -C 10 (preferably a C 1 -C 4 ) alkyl, alkenyl, ether or a thioether group; and R 11 and R 12 are independently selected from H or a C 1 -C 3 alkyl or alkenyl group, or a pharmaceutically acceptable salt thereof and methods for treating infections caused by protozoal, fungal and/or bacterial agents such as Trypanosoma cruzi, Mycobacterium spp., Leishmania spp., Cryptococcus spp., Aspergillus spp., Histoplasma spp., Candida spp., especially Candida albicans, Pneumocystis carinii, Trichophyton spp., Microsporum spp., Malassezia spp., Rhizopus spp., Pseudallescheria spp., Blastomyces dermatitidis and Coccidiodes spp., among others.

  本发明涉及式(I)的化合物：其中RA是C1-C10取代或未取代的线性、支链或环烷基或烯基或式(II)的苯基：RB是C1-C10取代或未取代的线性、支链或环烷基或烯基或式(III)的苯基：R1、R2、R3、R4、R5、R6、R7、R8、R9和R10各自独立地选自H、C1-C10(优选为C1-C4)烷基或烯基、CF3、F、Cl、Br、I、CN、NO2、NH2、NHR、NRR、COR（酰基）、OR（羟基或醚基）、CO2R（羧酸或酯基）或COSR（硫酯基），其中R是H或C1-C10(优选为C1-C4)烷基或烯基、未取代或取代的芳基（优选为苯基）或杂环基，或式(IV)的基团，其中R3是H、C1-C10(优选为C1-C4)烷基、烯基、醚或硫醚基；R11和R12各自独立地选自H或C1-C3烷基或烯基，或其药学上可接受的盐，以及用于治疗由原虫、真菌和/或细菌引起的感染的方法，例如Trypanosoma cruzi，Mycobacterium spp.，Leishmania spp.，Cryptococcus spp.，Aspergillus spp.，Histoplasma spp.，Candida spp.，特别是Candida albicans，Pneumocystis carinii，Trichophyton spp.，Microsporum spp.，Malassezia spp.，Rhizopus spp.，Pseudallescheria spp.，Blastomyces dermatitidis和Coccidioides spp.等。
• [EN] COMPOUNDS AND METHODS FOR THE INHIBITION OF TRYPANOSOMA CRUZ I<br/>[FR] COMPOSES ET PROCEDES D'INHIBITION DE TRYPANOSOMA CRUZI
  申请人：UNIV YALE

  公开号：WO2003006012A1

  公开（公告）日：2003-01-23

  The present invention relates to compounds according to the formula (I): Where RA is a C¿1?-C10 substituted or unsubstituted linear, branch-chained or cyclic alkyl or alkenyl group or a phenyl group according to the formula (II): R?B¿ is a C¿1?-C10 substituted or unsubstituted linear, branch-chained or cyclic alkyl or alkenyl group or a phenyl group of the formula (III): R?1, R2 , R3, R4, R5, R6, R7, R8, R9 and R10¿ are each independently selected from H, C¿1?-C10(preferably a C1-C4)alkyl or alkenyl group, CF3, F, Cl, Br, I, CN, NO2, NH2, NHR, NRR, COR (acyl group), OR (hydroxyl or ether group), CO2R (carboxylic acid or ester group ), or COSR (thioester group) where R is H or a C1-C10(preferably a C1-C4)alkyl or alkenyl group, an unsubstituted or substituted aryl (preferably, phenyl) or heterocycle group, or a (IV) group, where R3 is H, a C1-C10 (preferably a C1-C4) alkyl, alkenyl, ether or a thioether group; and R?11 and R12¿ are independently selected from H or a C¿1?-C3 alkyl or alkenyl group, or a pharmaceutically acceptable salt thereof and methods for treating infections caused by protozoal, fungal and/or bacterial agents such as Trypanosoma cruzi, Mycobacterium spp., Leishmania spp., Cryptococcus spp., Aspergillus spp., Histoplasma spp., Candida spp. especially Candida albicans, Pneumocystis carinii, Trichophyton spp., Microsporum spp., Malassezia spp., Rhizopus spp., Pseudallescheria spp., Blastomyces dermatitidis and Coccidiodes spp., among others.
• Heterologous expression and characterization of the sterol 14α-demethylase CYP51F1 from Candida albicans
  作者：Hyoung-Goo Park、Im-Soon Lee、Young-Jin Chun、Chul-Ho Yun、Jonathan B. Johnston、Paul R. Ortiz de Montellano、Donghak Kim

  DOI：10.1016/j.abb.2011.02.002

  日期：2011.5

  Lanosterol 14 alpha-demethylase (CYP51F1) from Candida albicans is known to be an essential enzyme in fungal sterol biosynthesis. Wild-type CYP51F1 and several of its mutants were heterologously expressed in Escherichia coli, purified, and characterized. It exhibited a typical reduced CO-difference spectrum with a maximum at 446 nm. Reconstitution of CYP51F1 with NADPH-P450 reductase gave a system that successfully converted lanosterol to its demethylated product. Titration of the purified enzyme with lanosterol produced a typical type I spectral change with K-d = 6.7 mu M. The azole antifungal agents econazole, fluconazole, ketoconazole, and itraconazole bound tightly to CYP51F1 with K-d values between 0.06 and 0.42 mu M. The CYP51F1 mutations F105L, D116E, Y132H, and R467K frequently identified in clinical isolates were examined to determine their effect on azole drug binding affinity. The azole K-d values of the purified F105L, D116E, and R467K mutants were little altered. A homology model of C. albicans CYP51F1 suggested that Tyr132 in the BC loop is located close to the heme in the active site, providing a rationale for the modified heme environment caused by the Y132H substitution. Taken together, functional expression and characterization of CYP51F1 provide a starting basis for the design of agents effective against C. albicans infections. (C) 2011 Elsevier Inc. All rights reserved.