Synthesis and Antiviral Activity of Dimeric Capsid-Binding Inhibitors of Human Rhinovirus (HRV)

2004 ◽  
Vol 57 (6) ◽  
pp. 553 ◽  
Author(s):  
Guy Y. Krippner ◽  
David K. Chalmers ◽  
Pauline C. Stanislawski ◽  
Simon P. Tucker ◽  
Keith G. Watson
Keyword(s):  
Antiviral Activity ◽  
Human Rhinovirus ◽  
Lower Activity ◽  
Active Compounds ◽  
Low Activity ◽  
Binding Inhibitors

A set of dimeric analogues of known rhinovirus capsid-binders Pleconaril 1 and Pirodavir 55 has been synthesized and tested against two representative human rhinovirus (HRV) strains. Dimers with linker lengths ranging from five atoms up to approximately 60 atoms were prepared by coupling various functionalized monomeric precursors. Many of the dimers showed activity against HRV, with the most active compounds being those with the shorter linking groups. The lower activity of all the dimers relative to similar monomeric compounds, and especially the low activity of the longest dimers, suggests that cooperative bivalent binding is not occurring with any of these compounds.

Cytokinin activity of some substituted ureas and thioureas

1966 ◽  
Vol 165 (999) ◽  
pp. 245-265 ◽  
Keyword(s):  
Biological Activity ◽  
Active Compound ◽  
Phenyl Ring ◽  
Chemical Structure ◽  
Lower Activity ◽  
Cytokinin Activity ◽  
Hydrogen Atoms ◽  
Detectable Activity ◽  
Low Activity

N , N '-Diphenylurea was shown to have reproducible cytokinin activity . Some 500 ureas, mainly of the N -monosubstituted and N , N '-disubstituted types, were tested an d about one half of these were active. Attempts were made to correlate chemical structure with biological activity. Although there are some exceptions to nearly every generalization it has been possible to formulate some principles. (1) Phenyl urea was the simplest active compound. (2) An HNCONH bridge conferred higher activity than an HNCSNH linkage and any other tested arrangement of the bridge gave inactive com pounds. (3) Compounds in which both amino hydrogen atoms on one or both sides of the bridge were substituted were of low activity or were inactive. (4) Many com pounds of the type R NHCONH 2 in which R = a substituted phenyl ring were tested. Ring substitution generally increased the activity and the highest activity was associated with meta substitution and the lowest with ortho . Compounds with electron-attracting substituents were generally more active than those with electron-donating substituents. Pyridyl compounds were active but com pounds with non-planar rings were inactive. (5) In compounds of the type R NHCONH R ' in which R and R ' were phenyl or substituted phenyl groups the highest activities were usually found in com pounds with one unsubstituted phenyl ring. Those with two substituted phenyl groups generally had lower activity. Some ureas showed detectable activity at 0.1 parts/10 6 . This was about four times less active than kinetin when tested in the tobacco pith assay.

scholarly journals The short-neurotoxin-binding regions on the α-chain of human and Torpedo californica acetylcholine receptors

1991 ◽  
Vol 274 (3) ◽  
pp. 849-854 ◽  
Author(s):  
K H Ruan ◽  
B G Stiles ◽  
M Z Atassi
Keyword(s):  
Binding Site ◽  
Acetylcholine Receptors ◽  
Binding Activity ◽  
Lower Activity ◽  
Binding Region ◽  
Torpedo Californica ◽  
Binding Regions ◽  
Alpha Bungarotoxin ◽  
Erabutoxin B ◽  
Low Activity

The continuous regions for short-neurotoxin binding on the alpha-chains of Torpedo californica (electric ray) and human acetylcholine receptors (AChR) were localized by reaction of 125I-labelled cobrotoxin (Cot) and erabutoxin b (Eb) with synthetic overlapping peptides spanning the entire extracellular part of the respective alpha-chains. On Torpedo AChR, five Cot-binding regions were found to reside within peptides alpha 1-16, alpha 23-38/alpha 34-49 overlap, alpha 100-115, alpha 122-138 and alpha 194-210. The Eb-binding regions were localized within peptides alpha 23-38/alpha 34-49/alpha 45-60 overlap, alpha 100-115 and alpha 122-138. The main binding activity for both toxins resided within region alpha 122-138. In previous studies we had shown that the binding of long alpha-neurotoxins [alpha-bungarotoxin (Bgt) and cobratoxin (Cbt)] involved the same regions on Torpedo AChR as well as an additional region within residues alpha 182-198. Thus region alpha 182-198, which is the strongest binding region for long neurotoxins on Torpedo AChR, was not a binding region for short neurotoxins. On human AChR, peptide alpha 122-138 possessed the highest activity with both toxins, and lower activity was found in the overlap alpha 23-38/alpha 34-49/alpha 45-60 and in peptide alpha 194-210. In addition, peptides alpha 100-115 and alpha 56-71 showed strong and medium binding activities to Eb, but low activity to Cot, whereas peptide alpha 1-16 exhibited low binding to Cot and no binding to Eb. Comparison with previous studies indicated that, for human AChR, the binding regions of short and long neurotoxins were essentially the same. The finding that the region within residues alpha 122-138 of both human and Torpedo AChR possessed the highest binding activity with short neurotoxins indicated that this region constitutes a universal binding site for long and short neurotoxins on AChR from various species.

Arylketotetramethylene Analogues of Disoxaril with Anti-Human Rhinovirus 14 Activity

1997 ◽  
Vol 8 (3) ◽  
pp. 235-242 ◽  
Author(s):  
A Mai ◽  
M Artico ◽  
G Sbardella ◽  
S Massa ◽  
A De Montis ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Human Rhinovirus

Arylketotetramethylene analogues of disoxaril (WIN 51711) were synthesized by reaction of 1-aryl-5-chloropentan-1-ones with 2-(4-hydroxyphenyl)-4,5-dihydro oxazoles, ethyl 4-hydroxybenzoates and 4-hydroxybenzonitrile. The new derivatives were tested for antiviral activity against various human rhinovirus (HRV) serotypes. The best activity was exhibited by the ethoxycarbonyl derivatives, whereas the oxazoline counterparts were less active and the cyano derivatives totally inactive. 5-[4-(4,5-Dihydro-2-oxazolyl)phenoxy]-1-(4-methoxyphenyl)pentan-1-one and ethyl 4-[5-(4-methylthiophenyl)-5-oxopentoxy] benzoate were more active than, and as active as, disoxaril, respectively, against HRV-14. Moreover, they were 10 times less cytotoxic.

scholarly journals Interaction of Natural Compounds in Licorice and Turmeric with HIV-NCp7 Zinc Finger Domain: Potential Relevance to the Mechanism of Antiviral Activity

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3563
Author(s):  
Runjing Wang ◽  
Yinyu Wei ◽  
Meiqin Wang ◽  
Pan Yan ◽  
Hongliang Jiang ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Zinc Finger ◽  
Binding Mode ◽  
Natural Compounds ◽  
Cd Spectroscopy ◽  
Scientific Basis ◽  
Noncovalent Interaction ◽  
Active Components ◽  
Active Compounds ◽  
Hiv Therapy

Nucleocapsid proteins (NCp) are zinc finger (ZF) proteins, and they play a central role in HIV virus replication, mainly by interacting with nucleic acids. Therefore, they are potential targets for anti-HIV therapy. Natural products have been shown to be able to inhibit HIV, such as turmeric and licorice, which is widely used in traditional Chinese medicine. Liquiritin (LQ), isoliquiritin (ILQ), glycyrrhizic acid (GL), glycyrrhetinic acid (GA) and curcumin (CUR), which were the major active components, were herein chosen to study their interactions with HIV-NCp7 C-terminal zinc finger, aiming to find the potential active compounds and reveal the mechanism involved. The stacking interaction between NCp7 tryptophan and natural compounds was evaluated by fluorescence. To elucidate the binding mode, mass spectrometry was used to characterize the reaction mixture between zinc finger proteins and active compounds. Subsequently, circular dichroism (CD) spectroscopy and molecular docking were used to validate and reveal the binding mode from a structural perspective. The results showed that ILQ has the strongest binding ability among the tested compounds, followed by curcumin, and the interaction between ILQ and the NCp7 zinc finger peptide was mediated by a noncovalent interaction. This study provided a scientific basis for the antiviral activity of turmeric and licorice.

scholarly journals Boronic Acids and Their Derivatives in Medicinal Chemistry: Synthesis and Biological Applications

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4323
Author(s):  
Mariana Pereira Silva ◽  
Lucília Saraiva ◽  
Madalena Pinto ◽  
Maria Emília Sousa
Keyword(s):  
Antiviral Activity ◽  
Boronic Acid ◽  
Medicinal Chemistry ◽  
Acid Group ◽  
Boronic Acids ◽  
Delivery Systems ◽  
Bioactive Molecules ◽  
Biological Applications ◽  
Active Compounds ◽  
Molecular Modification

Boron containing compounds have not been widely studied in Medicinal Chemistry, mainly due to the idea that this group could confer some toxicity. Nowadays, this concept has been demystified and, especially after the discovery of the drug bortezomib, the interest for these compounds, mainly boronic acids, has been growing. In this review, several activities of boronic acids, such as anticancer, antibacterial, antiviral activity, and even their application as sensors and delivery systems are addressed. The synthetic processes used to obtain these active compounds are also referred. Noteworthy, the molecular modification by the introduction of boronic acid group to bioactive molecules has shown to modify selectivity, physicochemical, and pharmacokinetic characteristics, with the improvement of the already existing activities. Besides, the preparation of compounds with this chemical group is relatively simple and well known. Taking into consideration these findings, this review reinforces the relevance of extending the studies with boronic acids in Medicinal Chemistry, in order to obtain new promising drugs shortly.

scholarly journals Antiviral activity of ginsenosides against coxsackievirus B3, enterovirus 71, and human rhinovirus 3

2014 ◽  
Vol 38 (3) ◽  
pp. 173-179 ◽  
Author(s):  
Jae-Hyoung Song ◽  
Hwa-Jung Choi ◽  
Hyuk-Hwan Song ◽  
Eun-Hye Hong ◽  
Bo-Ra Lee ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Enterovirus 71 ◽  
Coxsackievirus B3 ◽  
Human Rhinovirus
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