دورية أكاديمية
أعرض في EDS

Pharmacophore Virtual Screening Identifies Riboflavin as an Inhibitor of the Schistosome Cathepsin B1 Protease with Antiparasitic Activity.

التفاصيل البيبلوغرافية
العنوان: Pharmacophore Virtual Screening Identifies Riboflavin as an Inhibitor of the Schistosome Cathepsin B1 Protease with Antiparasitic Activity.
المؤلفون: Cogo RM; Universidade Federal de São Paulo-Campus Diadema, Curso de Pós-Graduação em Biologia Química da Unifesp, Rua São Nicolau 210, 2o andar, Centro, Diadema, São Paulo 09972-270, Brazil., Pavani TFA; Universidade Federal de São Paulo-Campus Diadema, Curso de Pós-Graduação em Biologia Química da Unifesp, Rua São Nicolau 210, 2o andar, Centro, Diadema, São Paulo 09972-270, Brazil., Mengarda ACA; Universidade Guarulhos, Núcleo de Pesquisa em Doenças Negligenciadas-NPDN, Praça Tereza Cristina 88, Guarulhos 09972-270, Brazil., Cajas RA; Universidade Guarulhos, Núcleo de Pesquisa em Doenças Negligenciadas-NPDN, Praça Tereza Cristina 88, Guarulhos 09972-270, Brazil., Teixeira TR; Universidade Guarulhos, Núcleo de Pesquisa em Doenças Negligenciadas-NPDN, Praça Tereza Cristina 88, Guarulhos 09972-270, Brazil., Fukui-Silva L; Universidade Guarulhos, Núcleo de Pesquisa em Doenças Negligenciadas-NPDN, Praça Tereza Cristina 88, Guarulhos 09972-270, Brazil., Sun YU; Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093-0021, United States., Liu LJ; Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093-0021, United States., Amarasinghe DK; Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093-0021, United States., Yoon MC; Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093-0021, United States., Santos-Filho OA; Instituto de Pesquisas de Produtos Naturais Walter Mors, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco H, Rio de Janeiro 21941-853, Brazil., de Moraes J; Universidade Guarulhos, Núcleo de Pesquisa em Doenças Negligenciadas-NPDN, Praça Tereza Cristina 88, Guarulhos 09972-270, Brazil., Caffrey CR; Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093-0021, United States., G G Rando D; Grupo de Pesquisas Químico-Farmacêuticas da Unifesp, Department of Pharmaceutical Sciences Rua São Nicolau, Universidade Federal de São Paulo-Campus Diadema, 210, 2o andar, Centro, Diadema, São Paulo 09972-270, Brazil.
المصدر: ACS omega [ACS Omega] 2024 May 30; Vol. 9 (23), pp. 25356-25369. Date of Electronic Publication: 2024 May 30 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101691658 Publication Model: eCollection Cited Medium: Internet ISSN: 2470-1343 (Electronic) Linking ISSN: 24701343 NLM ISO Abbreviation: ACS Omega Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Chemical Society, [2016]-
مستخلص: Schistosomiasis is a neglected disease of poverty that affects over 200 million people worldwide and relies on a single drug for therapy. The cathepsin B1 cysteine protease (SmCB1) of Schistosoma mansoni has been investigated as a potential target. Here, a structure-based pharmacophore virtual screening (VS) approach was used on a data set of approved drugs to identify potential antischistosomal agents targeting SmCB1. Pharmacophore (PHP) models underwent validation through receiver operating characteristics curves achieving values >0.8. The data highlighted riboflavin (RBF) as a compound of particular interest. A 1 μs molecular dynamics simulation demonstrated that RBF altered the conformation of SmCB1, causing the protease's binding site to close around RBF while maintaining the protease's overall integrity. RBF inhibited the activity of SmCB1 at low micromolar values and killed the parasite in vitro. Finally, in a murine model of S. mansoni infection, oral administration of 100 mg/kg RBF for 7 days significantly decreased worm burdens by ∼20% and had a major impact on intestinal and fecal egg burdens, which were decreased by ∼80%.
Competing Interests: The authors declare no competing financial interest.
(© 2024 The Authors. Published by American Chemical Society.)
References: Trends Parasitol. 2002 Mar;18(3):125-9. (PMID: 11854090)
Expert Opin Drug Discov. 2015 May;10(5):449-61. (PMID: 25835573)
J Chem Inf Model. 2005 Jan-Feb;45(1):177-82. (PMID: 15667143)
Parasit Vectors. 2018 Jan 31;11(1):65. (PMID: 29382360)
J Chem Inf Model. 2014 Jul 28;54(7):1951-62. (PMID: 24850022)
Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. (PMID: 17145705)
Int J Mol Sci. 2016 Jan 26;17(2):. (PMID: 26821017)
Am J Trop Med Hyg. 1995 Jul;53(1):61-2. (PMID: 7625534)
J Comput Chem. 2005 Dec;26(16):1701-18. (PMID: 16211538)
Pharm Biol. 2013 Nov;51(11):1347-54. (PMID: 23862567)
Sci Rep. 2022 Aug 18;12(1):14030. (PMID: 35982147)
ChemMedChem. 2023 Jun 15;18(12):e202300154. (PMID: 37009677)
Acta Trop. 2020 May;205:105350. (PMID: 31962096)
Parasitol Res. 1997;83(1):37-41. (PMID: 9000231)
J Chem Inf Model. 2010 Jul 26;50(7):1189-204. (PMID: 20572635)
Drug Discov Today. 2008 Oct;13(19-20):869-74. (PMID: 18703160)
Antimicrob Agents Chemother. 2019 Sep 16;63(12):. (PMID: 31527034)
ACS Infect Dis. 2021 Jan 8;7(1):189-201. (PMID: 33301315)
Acta Parasitol. 2023 Sep;68(3):481-495. (PMID: 37531011)
Biochim Biophys Acta. 2012 Jan;1824(1):68-88. (PMID: 22024571)
J Chem Theory Comput. 2021 Oct 12;17(10):6281-6291. (PMID: 34586825)
Drug Discov Today. 2022 Aug;27(8):2278-2287. (PMID: 35398562)
Front Chem. 2015 Apr 22;3:30. (PMID: 25954742)
J Biol Chem. 2019 Dec 6;294(49):18873-18880. (PMID: 31653697)
Drug Discov Today. 2006 Jul;11(13-14):607-15. (PMID: 16793529)
Microbiol Spectr. 2023 Aug 17;11(4):e0139323. (PMID: 37409934)
ACS Infect Dis. 2023 May 12;9(5):1046-1055. (PMID: 37083395)
J Comput Chem. 2010 Mar;31(4):671-90. (PMID: 19575467)
PLoS Med. 2007 Jan;4(1):e14. (PMID: 17214506)
Am J Physiol Cell Physiol. 2000 Feb;278(2):C270-6. (PMID: 10666022)
J Biol Chem. 2011 Oct 14;286(41):35770-35781. (PMID: 21832058)
Methods Mol Biol. 2020;2151:1-8. (PMID: 32451991)
J Clin Pharm Ther. 2017 Aug;42(4):394-403. (PMID: 28485121)
Mem Inst Oswaldo Cruz. 2002 Apr;97(3):381-5. (PMID: 12048569)
Structure. 2014 Dec 2;22(12):1786-1798. (PMID: 25456815)
Mol Biochem Parasitol. 2005 Oct;143(2):209-15. (PMID: 16076506)
J Chem Inf Model. 2006 Mar-Apr;46(2):728-35. (PMID: 16563003)
J Phys Chem B. 2013 Dec 5;117(48):14973-82. (PMID: 24195769)
J Med Chem. 2012 Jul 26;55(14):6582-94. (PMID: 22716043)
Sci Rep. 2021 Dec 6;11(1):23437. (PMID: 34873205)
Methods Mol Biol. 2020;2151:145-158. (PMID: 32452002)
Eur J Pharmacol. 2006 Oct 10;547(1-3):184-91. (PMID: 16962092)
J Chem Inf Model. 2016 Jul 25;56(7):1243-52. (PMID: 27280890)
J Comput Chem. 2008 Aug;29(11):1859-65. (PMID: 18351591)
Sci Rep. 2022 Nov 11;12(1):19320. (PMID: 36369516)
Parasitol Res. 1997;83(6):632-5. (PMID: 9211519)
J Mol Struct. 2023 Oct 15;1290:135871. (PMID: 37313328)
Metab Eng. 2021 Nov;68:46-58. (PMID: 34481976)
Nucleic Acids Res. 2016 Jan 4;44(D1):D1045-53. (PMID: 26481362)
Antimicrob Agents Chemother. 2015 May;59(5):2666-77. (PMID: 25712353)
Curr Opin Chem Biol. 2007 Aug;11(4):433-9. (PMID: 17652008)
Nat Chem Biol. 2005 Aug;1(3):146-8. (PMID: 16408018)
Front Pharmacol. 2022 Jun 17;13:917363. (PMID: 35784725)
ACS Cent Sci. 2017 Mar 22;3(3):143-147. (PMID: 28386587)
Trends Parasitol. 2004 May;20(5):241-8. (PMID: 15105025)
Mem Inst Oswaldo Cruz. 2011 Mar;106(2):153-7. (PMID: 21537673)
ACS Chem Biol. 2011 Jun 17;6(6):609-17. (PMID: 21375333)
Am J Clin Nutr. 1996 Jan;63(1):54-66. (PMID: 8604671)
ACS Infect Dis. 2021 May 14;7(5):1077-1088. (PMID: 33175511)
J Vitaminol (Kyoto). 1955 Feb 10;1(2):6-13. (PMID: 13264325)
Mol Biochem Parasitol. 2003 Sep;131(1):65-75. (PMID: 12967713)
Biochem Soc Trans. 2000;28(4):283-96. (PMID: 10961912)
Nat Methods. 2017 Jan;14(1):71-73. (PMID: 27819658)
Sci Rep. 2023 Nov 13;13(1):19735. (PMID: 37957227)
J Chem Inf Model. 2018 Feb 26;58(2):350-361. (PMID: 29308882)
J Clin Invest. 2008 Apr;118(4):1311-21. (PMID: 18382743)
Am J Trop Med Hyg. 1996 Aug;55(2):214-8. (PMID: 8780463)
J Biol Chem. 1997 Jan 10;272(2):1197-202. (PMID: 8995421)
تواريخ الأحداث: Date Created: 20240617 Latest Revision: 20240618
رمز التحديث: 20240618
مُعرف محوري في PubMed: PMC11170711
DOI: 10.1021/acsomega.4c03376
PMID: 38882094
قاعدة البيانات: MEDLINE
الوصف
تدمد:2470-1343
DOI:10.1021/acsomega.4c03376