Login Register Cart 0
Research Article

氟伐他汀对白色念珠菌CYP450羊毛甾醇14α-去甲基化酶的再利用，抗真菌治疗的目标酶：计算机和体外研究

卷 19, 期 7, 2019

页: [506 - 524] 页: 19

弟呕挨: 10.2174/1566524019666190520094644

价格: $65

摘要

背景：真菌感染的发病率显着增加。 具体而言，白色念珠菌感染的病例日益增加，并且它们对临床批准的药物的耐药性是人类主要关注的问题。 市场上有各种类型的抗真菌药物用于治疗这些感染，但不幸的是，它们都不能治疗感染。 目的：因此，在本研究中，我们通过使用计算机，体外和离体技术将已知药物（氟伐他汀）重新用于治疗白色念珠菌感染。 材料和方法：计算和体外技术。 结果：首先，利用结核分枝杆菌（1EA1）的晶体结构，开发并验证了白色念珠菌CYP45014α-羊毛甾醇脱甲基酶的简单模型。 此外，氟伐他汀与经验证的CYP45014α-羊毛甾醇去甲基化酶模型对接，并显示出与氟康唑的良好结合亲和力。 体外结果（百分比生长迟缓，真菌生长动力学，生物膜测试和抗真菌后测试）显示出良好的氟伐他汀抗真菌活性。 最后，MTT测定的结果显示氟伐他汀在小鼠脾细胞和胸腺细胞中的非细胞毒性作用。 结论：然而，需要进一步的体内研究来证实氟伐他汀作为抗真菌剂的全部作用。

关键词: 白色念珠菌，同源模型，氟伐他汀，对接研究，体外研究，离体研究。

« Previous Next »
[1]
Groll AH, Walsh TJ. Uncommon opportunistic fungi new nosocomial threats. Clin Microbiol Infect 2001; 7: 8-24.
[2]
Giraldo P, Von Nowakowski A, Gomes FA, et al. Vaginal colonization by Candida in asymptomatic women with and without a history of recurrent vulvovaginal candidiasis. Obstet Gynecol 2000; 95: 413-6.
[3]
Available at https://www.drugs.com data accessed on (2/4/18)
[4]
US Department of Health and Human Services (2012) Centers for Disease Control and Prevention (CDC). Antibiotic resistance threats in the United States. http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf Accessed 23 Sept 2015
[5]
Jabra-Rizk MA, Falkler WA, Meiller TF. Fungal biofilms and drug resistance. Emerg Infect Dis 2004; 10: 14-9.
[6]
Rana R, Sharma R, Kumar A. Repurposing of Existing Statin drugs for treatment of Microbial Infections: How much promising?. Infec disord drug targets 2018.
[http://dx.doi.org/doi: 10.2174/1871526518666180806123230.]
[7]
Schmidt M, Dzogbeta S, Boyer MP. Inhibition of Candida albicans by Fluvastatin Is dependent on pH. Biochem Res Int 2009; 2009: 151424.
[8]
Nash JD, Burgess DS, Talbert RL. Effect of fluvastatin and pravastatin, HMG-CoA reductase inhibitors, on fluconazole activity against Candida albicans. Indian J Med Microbiol 2002; 51: 105-9.
[9]
Chin NX, Weitzman I, Della-Latta P. In vitro activity of fluvastatin, a cholesterol-lowering agent, and synergy with flucanazole and itraconazole against Candida species and Cryptococcus neoformans. Antimicrob Agents Chemother 1997; 41: 850-2.
[10]
Chaffin WL. Candida albicans cell wall proteins. Microbiol Mol Biol Rev 2008; 72: 495-544.
[11]
Podust LM, Poulos TL, Waterman MR. Crystal structure of cytochrome P450 14α-sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors. Proc Natl Acad Sci USA 2001; 98: 3068-73.
[12]
Hess B, Kutzner C, Van Der Spoel D, et al. GROMACS 4. Algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput 2014; 4: 435-47.
[13]
Kant K, Lal UR, Kumar A, Ghosh M. A merged molecular docking, ADME-T and dynamics approaches towards the genus of Arisaema as herpes simplex virus type 1 and type 2 inhibitors. Comput Bioland Chem 2019; 78: 217-26.
[14]
Essmann U, Perera L, Berkowitz M, et al. A smooth particle mesh Ewald method. J Phys Chem Biophys 1995; 103: 8577-93.
[15]
SchuÈttelkopf AW,Van Aalten DM. PRODRG a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallographica Section D. Acta Crystallogr 2004; 60: 1355-63.
[16]
Grant BJ, Rodrigues AP, ElSawy KM, et al. Bio3d: anR package for the comparative analysis of protein structures. BMC Bioinformatics 2006; 22: 2695-6.
[17]
Amadei A, Linssen A, Berendsen HJ. Essential dynamics of proteins. Proteins: Struct, Funct, Bioinf. Proteins 1993; 17: 412-25.
[18]
García AE. Large-amplitude nonlinear motions in proteins. Phys Rev Lett 1992; 68: 2696-700.
[19]
Balsera MA, Wriggers W, Oono Y, et al. Principal component analysis and long time protein dynamics. J Phys Chem B 1996; 100: 2567-72.
[20]
Himedialabs.com/TD/LQ508.pdf for tryptone soya broth (data accessed on 2/4/18).
[21]
Gupta M, Sharma R, Kumar A. Comparative potential of Simvastatin, Rosuvastatin and Fluvastatin against bacterial infection: an in silico and in vitro study. Orient Pharm Exp Med 2019; 1-17.
[22]
Wu WS, Chen CC, Chuang YC, et al. Efficacy of combination oral antimicrobial agents against biofilm-embedded methicillin-resistant Staphylococcus aureus. J Microbiol Immunol Infect 2013; 46: 89-95.
[23]
Kumar A, Sharma N. Comparative efficacy of piperine and curcumin in deltamethrin induced splenic apoptosis and altered immune functions. Pestic Biochem Physiol 2015; 119: 16-27.
[24]
Jacob KS, Ganguly S, Kumar P, et al. Homology model, molecular dynamics simulation and novel pyrazole analogs design of Candida albicans CYP450 lanosterol 14 α-demethylase, a target enzyme for antifungal therapy. J Biomol Struct Dyn 2017; 35: 1446-63.
[25]
Yang AS, Honig B. An integrated approach to the analysis and modeling of protein sequences and structures. III. A comparative study of sequence conservation in protein structural families using multiple structural alignments1. Biochem Mol Biol J 2000; 301: 691-711.
[26]
Rost B. Twilight zone of protein sequence alignments. Korean J Chem Eng 1999; 12: 85-94.
[27]
Meyer T, Ferrer-Costa C, Pérez A, et al. Essential dynamics: a tool for efficient trajectory compression and management. J Chem Theory Comput 2006; 2: 251-8.
[28]
Li W, Shen J, Liu G, et al. Exploring coumarin egress channels in human cytochrome P450 2A6 by random acceleration and steered molecular dynamics simulations. Proteins 2011; 79: 271-81.
[29]
Shen J, Li W, Liu G, et al. Computational insights into the mechanism of ligand unbinding and selectivity of estrogen receptors. J Phys Chem B 2009; 113: 10436-44.
[30]
Nygaard R, Zou Y, Dror RO, et al. The dynamic process of β2-adrenergic receptor activation. Cell 2013; 152: 532-42.
[31]
Kruse AC, Hu J, Pan AC, et al. Structure and dynamics of the M3 muscarinic acetylcholine receptor. Nat 2012; 482: 552-9.
[32]
Lindorff-Larsen K, Piana S, Dror RO, et al. How fast-folding proteins fold. Sci 2011; 334: 517-20.
[33]
Piana S, Lindorff-Larsen K, Shaw DE. Atomic-level description of ubiquitin folding. Proc Natl Acad Sci USA 2013; 110: 5915-20.

Rights & Permissions Print Cite
Article Metrics
35
3
1
© 2024 Bentham Science Publishers | Privacy Policy