Betulin-derived compounds as inhibitors of alphavirus replication.

Published on Oct 19, 2009in Journal of Natural Products4.05
· DOI :10.1021/NP9003245
Leena Pohjala10
Estimated H-index: 10
 (UH: University of Helsinki), Sami Alakurtti15
Estimated H-index: 15
 + 2 AuthorsPäivi Tammela27
Estimated H-index: 27
Sources
Abstract
This paper describes inhibition of Semliki Forest virus (SFV) replication by synthetic derivatives of naturally occurring triterpenoid betulin (1). Chemical modifications were made to OH groups at C-3 and C-28 and to the C-20−C-29 double bond. A set of heterocyclic betulin derivatives was also assayed. A free or acetylated OH group at C-3 was identified as an important structural contributor for anti-SFV activity, 3,28-di-O-acetylbetulin (4) being the most potent derivative (IC50 value 9.1 μM). Betulinic acid (13), 28-O-tetrahydropyranylbetulin (17), and a triazolidine derivative (41) were also shown to inhibit Sindbis virus, with IC50 values of 0.5, 1.9, and 6.1 μM, respectively. The latter three compounds also had significant synergistic effects against SFV when combined with 3′-amino-3′-deoxyadenosine. In contrast to previous work on other viruses, the antiviral activity of 13 was mapped to take place in virus replication phase. The efficacy was also shown to be independent of external guanosine supple...
📖 Papers frequently viewed together
20064.38European Journal of Pharmaceutical Sciences
4 Authors (Sami Alakurtti, ..., Jari Yli-Kauhaluoma)
20103.64Bioorganic & Medicinal Chemistry
6 Authors (Sami Alakurtti, ..., Jari Yli-Kauhaluoma)
20054.53Current Medicinal Chemistry
2 Authors (Perumal Yogeeswari, Dharmarajan Sriram)
References48
Newest
Nov 20, 2008·Journal of Ethnopharmacology4.36
#1Guoying ZuoH-Index: 3
#2Genchun WangH-Index: 3
Last. Q. ZhaoH-Index: 1
view all 7 authors...
Abstract Ethnopharmacological relevance Traditional herbs are a valuable source of novel antibacterials in combating pathogenic isolates of methicillin-resistant Staphylococcus aureus (MRSA), a global nosocomial problem. Aim of the study To assess in vitro anti-MRSA activity of extracts from Chinese herbs. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were determined in the setting of clinical MRSA isolates. Materials and methods A collection of 19 p...
Source
Jun 1, 2008·Antiviral Research5.97
#1Leena Pohjala (UH: University of Helsinki)H-Index: 10
#2Vladimir BaraiH-Index: 1
Last. Tero Ahola (UH: University of Helsinki)H-Index: 41
view all 5 authors...
Abstract Several members of the widespread alphavirus group are pathogenic, but no therapy is available to treat these RNA virus infections. We report here a quantitative assay to screen for inhibitors of Semliki Forest virus (SFV) replication, and demonstrate the effects of 29 nucleosides on SFV and Sindbis virus replication. The anti-SFV assay developed is based on a SFV strain containing Renilla luciferase inserted after the nsP3 coding region, yielding a marker virus in which the luciferase ...
Source
Mar 1, 2008·The Lancet79.32
#1E Depoortere (ECDC: European Centre for Disease Prevention and Control)H-Index: 1
#2Stefania Salmaso (ISS: Istituto Superiore di Sanità)H-Index: 54
Last. Denis Coulombier (ECDC: European Centre for Disease Prevention and Control)H-Index: 18
view all 5 authors...
1 Rezza G, Nicoletti L, Angelini R, et al. Infection with Chikungunya virus in Italy: an outbreak in a temperate region. Lancet 2007; 370: 1840–46. 2 European Centre for Disease Prevention and Control. Meeting report: consultation on Chikungunya risk assessment for Europe. Stockholm: ECDC, 2006. http://ecdc.europa. eu/documents/pdf/Final_chik_meeting_ report.pdf (accessed Jan 30, 2008). 3 European Centre for Disease Prevention and Control. Mission report: Chikungunya in Italy. Stockholm: ECDC, 2...
Source
Jan 1, 2008·Antimicrobial Agents and Chemotherapy5.19
#1Weihong Lai (Duke University)H-Index: 9
#2Li Huang (Duke University)H-Index: 28
Last. Chin Ho Chen (Duke University)H-Index: 44
view all 6 authors...
Betulinic acid (BA) derivatives can inhibit human immunodeficiency virus type 1 (HIV-1) entry or maturation depending on side chain modifications. While BA derivatives with antimaturation activity have attracted considerable interest, the anti-HIV-1 profile and molecular mechanism of BA derivatives with anti-HIV-1 entry activity (termed BA entry inhibitors) have not been well defined. In this study, we have found that two BA entry inhibitors, IC9564 and A43D, exhibited a broad spectrum of anti-H...
Source
Jan 1, 2008·Journal of Natural Products4.05
#1José C. Aponte (University of Louisville)H-Index: 20
#2Abraham Vaisberg (UPCH: Cayetano Heredia University)H-Index: 28
Last. Gerald B. Hammond (University of Louisville)H-Index: 51
view all 9 authors...
The antiproliferative bioassay-guided fractionation of five Peruvian plants, Doliocarpus dentatus, Picramnia sellowii, Strychnos mitscherlichii, Iryanthera juruensis, and Croton alnifolius, led to the isolation and identification of their different major cytotoxic constituents, betulinic acid (1), nataloe-emodin (2), bisnordihydrotoxyferine (4), 2′,4′-dihydroxy-6′-methoxy-3,4-methylenedioxydihydrochalcone (5), and 2′,4′-dihydroxy-4,6′-dimethoxydihydrochalcone (6) and 12-O-tetradecanoylphorbol-13...
Source
Dec 1, 2007·The Lancet79.32
#1Giovanni Rezza (ISS: Istituto Superiore di Sanità)H-Index: 69
#2Loredana Nicoletti (ISS: Istituto Superiore di Sanità)H-Index: 27
Last. Antonio Cassone (ISS: Istituto Superiore di Sanità)H-Index: 84
view all 16 authors...
Summary Background Chikungunya virus (CHIKV), which is transmitted by Aedes spp mosquitoes, has recently caused several outbreaks on islands in the Indian Ocean and on the Indian subcontinent. We report on an outbreak in Italy. Methods After reports of a large number of cases of febrile illness of unknown origin in two contiguous villages in northeastern Italy, an outbreak investigation was done to identify the primary source of infection and modes of transmission. An active surveillance system ...
Source
Oct 1, 2007·Antimicrobial Agents and Chemotherapy5.19
#1Patrick F. Smith (UB: University at Buffalo)H-Index: 35
#2Abayomi B. Ogundele (UB: University at Buffalo)H-Index: 4
Last. David E. MartinH-Index: 19
view all 8 authors...
Bevirimat [3-O-(3,3-dimethylsuccinyl)betulinic acid] is the first in a new class of anti-human immunodeficiency virus (HIV) drugs that inhibit viral maturation by specifically blocking cleavage of the Gag capsid (CA) precursor, CA-SP1, to mature CA protein, resulting in defective core condensation and release of immature noninfectious virions. Four cohorts of six HIV-infected adults, with CD4 counts of >200 and plasma viral loads of 5,000 to 250,000 transcripts/ml and not currently receiving ant...
Source
Jul 31, 2007·Journal of Medicinal Chemistry7.45
#1Chih-Chun Wen (AS: Academia Sinica)H-Index: 8
#2Yueh-Hsiung Kuo (PRC: China Medical University (PRC))H-Index: 67
Last. Ning-Sun Yang (AS: Academia Sinica)H-Index: 40
view all 15 authors...
In this study, 221 phytocompounds were evaluated for activity against anti-severe acute respiratory syndrome associated coronavirus (SARS-CoV) activities using a cell-based assay measuring SARS-CoV-induced cytopathogenic effect on Vero E6 cells. Ten diterpenoids (1−10), two sesquiterpenoids (11 and 12), two triterpenoids (13 and 14), five lignoids (15−19), curcumin (20), and reference controls niclosamide (21) and valinomycin (22) were potent inhibitors at concentrations between 3.3 and 10 μM. T...
Source
May 8, 2007·Proceedings of the National Academy of Sciences of the United States of America11.21
#1Yanmei Li (CAS: Chinese Academy of Sciences)H-Index: 4
#2Lihua WangH-Index: 19
Last. Xiaojiang HaoH-Index: 20
view all 12 authors...
Plants have evolved multiple mechanisms to selectively suppress pathogens by production of secondary metabolites with antimicrobial activities. Therefore, direct selections for antiviral compounds from plants can be used to identify new agents with potent antiviral activity but not toxic to hosts. Here, we provide evidence that a class of compounds, seco-pregnane steroid glaucogenin C and its monosugar-glycoside cynatratoside A of Strobilanthes cusia and three new pantasugar-glycosides of glauco...
Source
Chikungunya is an arboviral disease transmitted by aedes mosquitoes. The virus was fi rst isolated in 1953 in Tanzania. Chikungunya virus is a member of the genus Alphavirus and the family Togaviridae. The disease typically consists of an acute illness characterised by fever, rash, and incapacitating arthralgia. The word chikungunya, used for both the virus and the disease, means “to walk bent over” in some east African languages, and refers to the eff ect of the joint pains that characterise th...
Source
12345
Cited By72
Newest
Jul 29, 2021·Viruses5.83
#1Michael Kirstgen (University of Giessen)H-Index: 3
#2Simon Franz Müller (University of Giessen)H-Index: 5
Last. Dieter Glebe (University of Giessen)H-Index: 30
view all 11 authors...
The hepatic bile acid transporter Na+/taurocholate co-transporting polypeptide (NTCP) was identified in 2012 as the high-affinity hepatic receptor for the hepatitis B and D viruses (HBV/HDV). Since then, this carrier has emerged as promising drug target for HBV/HDV virus entry inhibitors, but the synthetic peptide Hepcludex® of high molecular weight is the only approved HDV entry inhibitor so far. The present study aimed to identify small molecules as novel NTCP inhibitors with anti-viral activi...
Source
Jul 15, 2021·Chemistry of Natural Compounds0.81
#1V. A. Vydrina (RAS: Russian Academy of Sciences)H-Index: 6
#2R. R. Sayakhov (RAS: Russian Academy of Sciences)H-Index: 1
Last. G. Yu. Ishmuratov (RAS: Russian Academy of Sciences)H-Index: 12
view all 6 authors...
A new synthesis of 3-oxo-28-hydroxylup-20(29)-ene from the available natural triterpenoid betulin was developed. α,ω-Diketodiesters were prepared for the first time by different methods from 3-oxo-28-hydroxylup-20(29)-ene and a series of natural dicarboxylic acids. Steglich reaction conditions gave the highest yields. One of the synthesized α,ω-diketodiesters was moderately active in vitro against A-549 lung carcinoma.
Source
Jul 12, 2021·The Journal of Antibiotics2.65
#1Oxana B. Kazakova (RAS: Russian Academy of Sciences)H-Index: 17
#2Elena V. Tretyakova (RAS: Russian Academy of Sciences)H-Index: 9
Last. Dmitry S. BaevH-Index: 10
view all 3 authors...
A series of semisynthetic triterpenoids with A-ring azepano- and A-seco-fragments as well as hydrazido/hydrazono-substituents at C3 and C28 has been synthesized and evaluated for antimicrobial activity against key ESKAPE pathogens and DNA viruses (HSV-1, HCMV, HPV-11). It was found that azepanouvaol 8, 3-amino-3,4-seco-4(23)-en derivatives of uvaol 21 and glycyrrhetol-dien 22 as well as azepano-glycyrrhetol-tosylate 32 showed strong antimicrobial activities against MRSA with MIC ≤ 0.15 μM that e...
Source
Many Picornaviridae family members infect humans. Enterovirus (EV), the largest genus, causes diseases ranging from the common cold to fatal heart disease and paralysis. Human parechoviruses (HPeV) are at least as prevalent as EVs. Currently, no antipicornavirus drugs are used clinically and the large number of viruses precludes vaccination. New drugs are therefore required. Picornavirus infection exploits viral and host proteins, lipids and cellular systems, all potentially targetable by inhibi...
May 7, 2021·European Journal of Organic Chemistry3.02
#1Jevgeņija Lugiņina (Riga Technical University)H-Index: 7
#2Martin Lindén (University of Mainz)H-Index: 15
Last. Māris Turks (Riga Technical University)H-Index: 15
view all 10 authors...
Source
May 1, 2021·Medicinal Chemistry Research1.97
#1Carolina Sousa Ponciano (UFJF: Universidade Federal de Juiz de Fora)H-Index: 1
#2Eloah P. Ávila (UFJF: Universidade Federal de Juiz de Fora)H-Index: 7
Last. Mauro V. de Almeida (UFJF: Universidade Federal de Juiz de Fora)H-Index: 25
view all 5 authors...
Flavivirus is a genus that comprises more than 70 viruses with common characteristics and causes many of the most prevalent infections in the world. These viruses affect more people than any other genus. However, compared to other viral diseases, priorities are low in the context of public health perhaps due to their prevalence in developing countries. A safe and efficacious vaccine would be the ideal way to prevent diseases caused by Flavivirus spp., however, the treatment of most of these infe...
Source
Mar 25, 2021·Pharmaceutics6.32
#4Ki-Hyun Kim (SKKU: Sungkyunkwan University)H-Index: 20
Cornus walteri (Cornaceae), known as Walter's dogwood, has been used to treat dermatologic inflammation and diarrheal disease in traditional oriental medicine. As part of an ongoing research project to discover natural products with biological activities, the anti-inflammatory potential of compounds from C. walteri in lipopolysaccharide (LPS)-stimulated mouse RAW 264.7 macrophages were explored. Phytochemical analysis of the methanol extract of the stem and stem bark of C. walteri led to the iso...
Source
Feb 12, 2021·Nanomaterials5.08
#1Anna Grigoreva
#2E. KolobovaH-Index: 8
Last. Alexey PestryakovH-Index: 26
view all 9 authors...
Herein, it has been shown that betulin can be transformed into its biologically active oxo-derivatives (betulone, betulinic and betulonic aldehydes) by liquid-phase oxidation over supported silver catalysts under mild conditions. In order to identify the main factors determining the catalytic behavior of nanosilver catalysts in betulin oxidation, silver was deposited on various alumina supports (γ-alumina and boehmite) using deposition–precipitation with NaOH and incipient wetness impregnation m...
Source
#1Nourhan Hisham ShadyH-Index: 5
#2Khayrya A. YoussifH-Index: 6
Last. Usama Ramadan Abdelmohsen (Minia University)H-Index: 26
view all 7 authors...
The acute respiratory syndrome caused by the novel coronavirus (SARS-CoV-2) caused severe panic all over the world. The coronavirus (COVID-19) outbreak has already brought massive human suffering and major economic disruption and unfortunately, there is no specific treatment for COVID-19 so far. Herbal medicines and purified natural products can provide a rich resource for novel antiviral drugs. Therefore, in this review, we focused on the sterols and triterpenes as potential candidates derived ...
Source
Dec 10, 2020·Scientific Reports4.38
#1Michael Kirstgen (University of Giessen)H-Index: 3
#2Kira Alessandra Alicia Theresa Lowjaga (University of Giessen)H-Index: 2
Last. Joachim Geyer (University of Giessen)H-Index: 26
view all 9 authors...
Current treatment options against hepatitis B and D virus (HBV/HDV) infections have only limited curative effects. Identification of Na+/taurocholate co-transporting polypeptide (NTCP) as the high-affinity hepatic receptor for both viruses in 2012 enables target-based development of HBV/HDV cell-entry inhibitors. Many studies already identified appropriate NTCP inhibitors. However, most of them interfere with NTCP's physiological function as a hepatic bile acid transporter. To overcome this draw...
Source
12345678
This website uses cookies.
We use cookies to improve your online experience. By continuing to use our website we assume you agree to the placement of these cookies.
To learn more, you can find in our Privacy Policy.