scholarly journals Structural requirements of thiol compounds in the inhibition of human liver iodothyronine 5′-deiodinase

1984 ◽  
Vol 217 (2) ◽  
pp. 485-491 ◽  
Author(s):  
R Harbottle ◽  
S J Richardson
Keyword(s):  
Human Liver ◽  
Thiol Group ◽  
Structural Features ◽  
Inhibitory Potency ◽  
Structural Requirements ◽  
Thiol Compounds ◽  
Alkyl Derivatives ◽  
Free Thiol Group ◽  
Thiol Form ◽  
Derivatives Of

2-Thiouracil and a number of its alkyl derivatives are known to inhibit the enzymic 5′-deodination of thyroxine to 3,5,3′-tri-iodothyronine. The structural requirements for inhibition of iodothyronine 5′-deiodinase were investigated by using a washed postmitochondrial particulate fraction of human liver. A series of sulphur-containing derivatives of pyrimidine, pyridine, imidazole, benzene and urea, capable of existing in a thiol form, were incubated at several concentrations with the enzyme preparation in the presence of thyroxine and dithioerythritol (cofactor). The degree of inhibition by the respective compounds of the production of 3,5,3′-tri-iodothyronine was studied in relation to their structural features. The major observations were: (i) a free thiol group is essential; (ii) compounds that do not possess a polar hydrogen atom spatially configured so that it is proximal to the thiol group are poor inhibitors; (iii) aromatic characteristics in the presence of requirements (i) and (ii) lead to the expression of potent inhibitory properties; (iv) modification of potent inhibitors by the introduction of hydrophilic substituents reduces the inhibitory potency.

scholarly journals Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties

2021 ◽  
Vol 22 (19) ◽  
pp. 10318
Author(s):  
Daria A. Belinskaia ◽  
Polina A. Voronina ◽  
Vladimir I. Shmurak ◽  
Richard O. Jenkins ◽  
Nikolay V. Goncharov
Keyword(s):  
Vascular Endothelial Cells ◽  
Glycated Albumin ◽  
Decisive Role ◽  
Thiol Group ◽  
Structural Features ◽  
Endothelial Glycocalyx ◽  
Toxic Substances ◽  
Free Thiol Group ◽  
Health And Disease ◽  
Almost All

Being one of the main proteins in the human body and many animal species, albumin plays a decisive role in the transport of various ions—electrically neutral and charged molecules—and in maintaining the colloidal osmotic pressure of the blood. Albumin is able to bind to almost all known drugs, as well as many nutraceuticals and toxic substances, largely determining their pharmaco- and toxicokinetics. Albumin of humans and respective representatives in cattle and rodents have their own structural features that determine species differences in functional properties. However, albumin is not only passive, but also an active participant of pharmacokinetic and toxicokinetic processes, possessing a number of enzymatic activities. Numerous experiments have shown esterase or pseudoesterase activity of albumin towards a number of endogeneous and exogeneous esters. Due to the free thiol group of Cys34, albumin can serve as a trap for reactive oxygen and nitrogen species, thus participating in redox processes. Glycated albumin makes a significant contribution to the pathogenesis of diabetes and other diseases. The interaction of albumin with blood cells, blood vessels and tissue cells outside the vascular bed is of great importance. Interactions with endothelial glycocalyx and vascular endothelial cells largely determine the integrative role of albumin. This review considers the esterase, antioxidant, transporting and signaling properties of albumin, as well as its structural and functional modifications and their significance in the pathogenesis of certain diseases.

Structure-activity studies on open-chain analogues of nucleosides: Inhibition of S-adenosyl-L-homocysteine hydrolase and antiviral activity 1. Neutral open-chain analogues

1985 ◽  
Vol 50 (1) ◽  
pp. 245-261 ◽  
Author(s):  
Antonín Holý ◽  
Ivan Votruba ◽  
Erik De Clercq
Keyword(s):  
Antiviral Activity ◽  
Alkyl Chain ◽  
Structural Features ◽  
Inhibitory Effects ◽  
Open Chain ◽  
Structure Activity ◽  
Vicinal Diol ◽  
Alkyl Derivatives ◽  
Vesicular Stomatitis ◽  
Derivatives Of

Over 70 alkyl derivatives of purine bases were examined for their inhibitory effects toward rat liver S-adenosyl-L-homocysteine hydrolase and their antiviral activity. The following structural features must be fulfilled by an inhibitor of SAH-hydrolase: an intact adenine moiety, an alkyl chain bound at the 9-position and bearing a vicinal diol at the 2',3'-position, with 2S configuration. An additional substitution at the 3-position lowers or annihilates the inhibitory activity. The enzyme inhibition is reversible. Some of the compounds are substrates of adenosine aminohydrolase. All inhibitors of SAH-hydrolase exhibit antiviral activity, e.g. against vesicular stomatitis virus and vaccinia virus in cell culture, and this antiviral correlates with the inhibition of SAH-hydrolase.

Synthesis, Docking Studies into CDK-2 and Anticancer Activity of New Derivatives Based Pyrimidine Scaffold and Their Derived Glycosides

2019 ◽  
Vol 19 (13) ◽  
pp. 1093-1110 ◽  
Author(s):  
Adel A.H. Abdel Rahman ◽  
Ibrahim F. Nassar ◽  
Amira K.F. Shaban ◽  
Dina S. EL-Kady ◽  
Hanem M. Awad ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Human Liver ◽  
Docking Studies ◽  
Cyclin Dependent Kinase ◽  
Binding Interaction ◽  
Enzyme Active Site ◽  
Human Liver Cancer ◽  
Amino Derivatives ◽  
Activity Behavior ◽  
Derivatives Of

Background & Objective:New diaryl-substituted pyrimidinedione compounds, their thioxo derivatives as well as their bicyclic thiazole compounds were synthesized and characterized.Methods:The glycosylamino derivatives of the synthesized disubstituted derivatives of the pyrimidine scaffold were also prepared via reaction of the N3-amino derivatives with a number of monosaccharides followed by acetylation.Results:The anticancer activity of the synthesized compounds was studied against human liver cancer (HepG2) and RPE-1cell lines. Compounds 2a, 2b, 3a and 12 showed potent activities with IC50 results comparable to that of doxorubicin.Conclusion:Docking investigations into Cyclin-dependent kinase 2 (CDK-2) enzyme, a potential target for cancer medication, were also reported showing the possible binding interaction into the enzyme active site to support their activity behavior.

7-O-Alkyl derivatives of daunomycinone

1984 ◽  
Vol 49 (1) ◽  
pp. 313-319 ◽  
Author(s):  
Věra Přikrylová ◽  
Petr Sedmera ◽  
Josef V. Jizba ◽  
Jindřich Vokoun ◽  
Helena Lipavská ◽  
...  
Keyword(s):  
H Nmr ◽  
Toluenesulfonic Acid ◽  
Alkyl Derivatives ◽  
Derivatives Of

Reaction of daunomycinone (I) with alcohols and p-toluenesulfonic acid produces a mixture (~3 : 1) of its (7S)- and (7R)-O-alkyl derivatives II-IX. According to the 1H NMR evidence, the alicyclic ring exists in the 9H8 conformation in (7R)-O-alkyl derivatives, on the contrary to (7S)-epimers and 7-epi-daunomycinone that adopt the 8H9 conformation.

Polarized fluorescense of alkyl derivatives of fluorescein, MitoFluo and C8-Fl, in solutions with liposomes

2020 ◽  
Author(s):  
D.M. Beltukova ◽  
V.P. Belik ◽  
Y.N. Antonenko ◽  
A.A. Bogdanov ◽  
G.A. Korshunova ◽  
...  
Keyword(s):  
Alkyl Derivatives ◽  
Derivatives Of

scholarly journals 1250. Novel Boronic Acid Transition State Analogs (BATSI) with in vitro inhibitory activity against class A, B and C β-lactamases

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S643-S643
Author(s):  
Maria F Mojica ◽  
Christopher Bethel ◽  
Emilia Caselli ◽  
Magdalena A Taracila ◽  
Fabio Prati ◽  
...  
Keyword(s):  
Active Site ◽  
Inhibitory Activity ◽  
Covalent Bond ◽  
Thiol Group ◽  
Viable Cell ◽  
Free Thiol ◽  
Transition State Analogs ◽  
Cell Counts ◽  
Free Thiol Group

Abstract Background Catalytic mechanisms of serine β-lactamases (SBL; classes A, C and D) and metallo-β-lactamases (MBLs) have directed divergent strategies towards inhibitor design. SBL inhibitors act as high affinity substrates that -as in BATSIs- form a reversible, dative covalent bond with the conserved active site Ser. MBL inhibitors bind the active-site Zn2+ ions and displace the nucleophilic OH-. Herein, we explore the efficacy of a series of BATSI compounds with a free-thiol group at inhibiting both SBL and MBL. Methods Exploratory compounds were synthesized using stereoselective homologation of (+) pinandiol boronates to introduce the amino group on the boron-bearing carbon atom, which was subsequently acylated with mercaptopropanoic acid. Representative SBL (KPC-2, ADC-7, PDC-3 and OXA-23) and MBL (IMP-1, NDM-1 and VIM-2) were purified and used for the kinetic characterization of the BATSIs. In vitro activity was evaluated by a modified time-kill curve assay, using SBL and MBL-producing strains. Results Kinetic assays revealed that IC50 values ranged from 1.3 µM to >100 µM for this series. The best compound, s08033, demonstrated inhibitory activity against KPC-2, VIM-2, ADC-7 and PDC-3, with IC50 in the low μM range. Reduction of at least 1.5 log10-fold of viable cell counts upon exposure to sub-lethal concentrations of antibiotics (AB) + s08033, compared to the cells exposed to AB alone, demonstrated the microbiological activity of this novel compound against SBL- and MBL-producing E. coli (Table 1). Table 1 Conclusion Addition of a free-thiol group to the BATSI scaffold increases the range of these compounds resulting in a broad-spectrum inhibitor toward clinically important carbapenemases and cephalosporinases. Disclosures Robert A. Bonomo, MD, Entasis, Merck, Venatorx (Research Grant or Support)

scholarly journals Conjugate of Thiol and Guanidyl Units with Oligoethylene Glycol Linkage for Manipulation of Oxidative Protein Folding

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 879
Author(s):  
Shunsuke Okada ◽  
Motonori Matsusaki ◽  
Masaki Okumura ◽  
Takahiro Muraoka
Keyword(s):  
Protein Folding ◽  
Active Sites ◽  
Biological Process ◽  
Thiol Group ◽  
Native Conformation ◽  
Thiol Compounds ◽  
Oxidative Protein Folding ◽  
Redox Active ◽  
A Cell ◽  
Protein Disulfide

Oxidative protein folding is a biological process to obtain a native conformation of a protein through disulfide-bond formation between cysteine residues. In a cell, disulfide-catalysts such as protein disulfide isomerase promote the oxidative protein folding. Inspired by the active sites of the disulfide-catalysts, synthetic redox-active thiol compounds have been developed, which have shown significant promotion of the folding processes. In our previous study, coupling effects of a thiol group and guanidyl unit on the folding promotion were reported. Herein, we investigated the influences of a spacer between the thiol group and guanidyl unit. A conjugate between thiol and guanidyl units with a diethylene glycol spacer (GdnDEG-SH) showed lower folding promotion effect compared to the thiol–guanidyl conjugate without the spacer (GdnSH). Lower acidity and a more reductive property of the thiol group of GdnDEG-SH compared to those of GdnSH likely resulted in the reduced efficiency of the folding promotion. Thus, the spacer between the thiol and guanidyl groups is critical for the promotion of oxidative protein folding.

Synthesis and reactivity of halide, hydride, and alkyl derivatives of (pentamethylcyclopentadienyl)(bisphosphine)iron(II)

1990 ◽  
Vol 9 (1) ◽  
pp. 260-265 ◽  
Author(s):  
Rocco A. Paciello ◽  
Juan M. Manriquez ◽  
John E. Bercaw
Keyword(s):  
Alkyl Derivatives ◽  
Derivatives Of

The Chemical Structure Responsible for the Deactivating Effect of Compounds Which Protect Rubber from Deterioration by Oxygen

1951 ◽  
Vol 24 (3) ◽  
pp. 638-639
Author(s):  
Jean Le Bras ◽  
Jacques Le Foll
Keyword(s):  
Nitrogen Atom ◽  
Systematic Study ◽  
Chemical Structure ◽  
Thiol Group ◽  
Vulcanized Rubber ◽  
Thiol Form

Abstract One of the present authors has already offered evidence which indicates the existence of a deactivating effect, whereby vulcanized rubber is protected against deterioration by oxygen. This effect is evident with such compounds as mercaptobenzimidazole (I), mercaptobenzoxazole, and ethylene-bis (N,N′-phenylthiourea) (II), and the phenomenon seems to be connected in some way with the presence in the molecule of a thiol group united to a nitrogen atom under such conditions that the possible tautomerism between the thion and thiol forms (III) is probably displaced toward the thiol form. We have completed these earlier experiments by a more systematic study, which has included an examination of the influence of cyclization, the nature of the ring, and hetero atoms.

The Alkyl Derivatives of Halogen Phenols and their Bactericidal Action. II. Bromophenols

1933 ◽  
Vol 55 (11) ◽  
pp. 4657-4662 ◽  
Author(s):  
Emil Klarmann ◽  
Louis W. Gates ◽  
Vladimir A. Shternov ◽  
Philip H. Cox
Keyword(s):  
Bactericidal Action ◽  
Alkyl Derivatives ◽  
Derivatives Of
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