Hitting a Moving Target: How Does anN-Methyl Group Impact Biological Activity?

ChemMedChem ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. 881-892 ◽  
Author(s):  
Yen Chin Koay ◽  
Nicole L. Richardson ◽  
Samantha S. Zaiter ◽  
Jessica Kho ◽  
Sheena Y. Nguyen ◽  
...  
Keyword(s):  
Biological Activity ◽  
Moving Target ◽  
Methyl Group

scholarly journals Entomopathogenic Filamentous Fungi as Biocatalysts in Glycosylation of Methylflavonoids

Catalysts ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1148
Author(s):  
Agnieszka Krawczyk-Łebek ◽  
Monika Dymarska ◽  
Tomasz Janeczko ◽  
Edyta Kostrzewa-Susłow
Keyword(s):  
Biological Activity ◽  
Filamentous Fungi ◽  
Beauveria Bassiana ◽  
Biological Activities ◽  
Isaria Fumosorosea ◽  
Methyl Group ◽  
Group 2 ◽  
Pharmacological Application

Flavonoids are known for their numerous biological activities; however, their pharmacological application is limited by poor bioavailability. Glycosides are usually more stable and more soluble in water and in this form, flavonoids are present in nature. Likewise, the presence of the methyl group in the flavonoid skeleton results in facilitated absorption and greater bioavailability. Entomopathogenic filamentous fungi are effective in the biotransformation of flavonoids; they are known especially for efficient glycosylation. In the current study we used strains of Beauveria bassiana KCH J1.5 and Isaria fumosorosea KCH J2 to biotransform flavonoids with a single methyl group. 2′-Hydroxy-5′-methylchalcone was biotransformed by both strains into 2′-hydroxy-5′-methylchalcone 3-O-β-D-(4″-O-methyl)-glucopyranoside. In the culture of B. bassiana KCH J1.5 four products were obtained from 6-methylflavanone: 4′-hydroxy-6-methylflavanone 3′-O-β-D-(4″-O-methyl)-glucopyranoside; 4′-hydroxyflavanone 6-methylene-O-β-D-(4″-O-methyl)-glucopyranoside; 6-hydroxymethylflavanone 3′-O-β-D-(4″-O-methyl)-glucopyranoside and 4′-hydroxy-6-hydroxymethylflavanone 3′-O-β-D-(4″-O-methyl)-glucopyranoside. Biotransformation with I. fumosorosea KCH J2 as a biocatalyst resulted in the formation of 6-methylflavanone 4′-O-β-D-(4″-O-methyl)-glucopyranoside and 2-phenyl-6-methylchromane 4-O-β-D-(4″-O-methyl)-glucopyranoside. All of these flavonoids can be used in biological activity tests and can be useful in studies concerning structure—bioactivity relationships.

scholarly journals Synthesis, Biological Evaluation and Docking Studies of 13-Epimeric 10-fluoro- and 10-Chloroestra-1,4-dien-3-ones as Potential Aromatase Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1783 ◽  
Author(s):  
Rebeka Jójárt ◽  
Péter Traj ◽  
Édua Kovács ◽  
Ágnes Horváth ◽  
Gyula Schneider ◽  
...  
Keyword(s):  
Biological Activity ◽  
Inhibitory Action ◽  
Molecular Level ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Computational Simulations ◽  
Simultaneous Application ◽  
Methyl Group ◽  
Ic50 Values

Fluorination of 13-epimeric estrones and their 17-deoxy counterparts was performed with Selectfluor as the reagent. In acetonitrile or trifluoroacetic acid (TFA), 10β-fluoroestra-1,4-dien-3-ones were formed exclusively. Mechanistic investigations suggest that fluorinations occurred via SET in acetonitrile, but another mechanism was operative in TFA. Simultaneous application of N-chlorosuccinimide (NCS) and Selectfluor in TFA led to a 1.3:1 mixture of 10β-fluoroestra-1,4-dien-3-one and 10β-chloroestra-1,4-dien-3-one as the main products. The potential inhibitory action of the 10-fluoro- or 10-chloroestra-1,4-dien-3-one products on human aromatase was investigated via in vitro radiosubstrate incubation. The classical estrane conformation with trans ring anellations and a 13β-methyl group seems to be crucial for the inhibition of the enzyme, while test compounds bearing the 13β-methyl group exclusively displayed potent inhibitory action with submicromolar or micromolar IC50 values. Concerning molecular level explanation of biological activity or inactivity, computational simulations were performed. Docking studies reinforced that besides the well-known Met374 H-bond connection, the stereocenter in the 13 position has an important role in the binding affinity. The configuration inversion at C-13 results in weaker binding of 13α-estrone derivatives to the aromatase enzyme.

scholarly journals Synthesis and Biological Activity of Sterol 14α-Demethylase and Sterol C24-Methyltransferase Inhibitors

Molecules ◽  
2018 ◽  
Vol 23 (7) ◽  
pp. 1753 ◽  
Author(s):  
David Leaver
Keyword(s):  
Biological Activity ◽  
Drug Target ◽  
Human African Trypanosomiasis ◽  
Neglected Tropical Diseases ◽  
Pathogenic Fungi ◽  
Molecular Target ◽  
Tropical Diseases ◽  
Sterol Metabolism ◽  
Methyl Group ◽  
Animal Host

Sterol 14α-demethylase (SDM) is essential for sterol biosynthesis and is the primary molecular target for clinical and agricultural antifungals. SDM has been demonstrated to be a valid drug target for antiprotozoal therapies, and much research has been focused on using SDM inhibitors to treat neglected tropical diseases such as human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis. Sterol C24-methyltransferase (24-SMT) introduces the C24-methyl group of ergosterol and is an enzyme found in pathogenic fungi and protozoa but is absent from animals. This difference in sterol metabolism has the potential to be exploited in the development of selective drugs that specifically target 24-SMT of invasive fungi or protozoa without adversely affecting the human or animal host. The synthesis and biological activity of SDM and 24-SMT inhibitors are reviewed herein.

scholarly journals Biotransformation of Bicyclic Halolactones with a Methyl Group in the Cyclohexane Ring into Hydroxylactones and Their Biological Activity

Molecules ◽  
2016 ◽  
Vol 21 (11) ◽  
pp. 1453 ◽  
Author(s):  
Katarzyna Wińska ◽  
Małgorzata Grabarczyk ◽  
Wanda Mączka ◽  
Barbara Żarowska ◽  
Gabriela Maciejewska ◽  
...  
Keyword(s):  
Biological Activity ◽  
Cyclohexane Ring ◽  
Methyl Group

scholarly journals The 7[prime]-Methyl Group of Abscisic Acid Is Critical for Biological Activity in Wheat Embryo Germination

1994 ◽  
Vol 106 (4) ◽  
pp. 1279-1284 ◽  
Author(s):  
M. K. Walker-Simmons ◽  
P. A. Rose ◽  
A. C. Shaw ◽  
S. R. Abrams
Keyword(s):  
Biological Activity ◽  
Abscisic Acid ◽  
Embryo Germination ◽  
Wheat Embryo ◽  
Methyl Group

The glutarimide antibiotic 9-methylstreptimidone: Structure, biogenesis and biological activity

1976 ◽  
Vol 29 (3) ◽  
pp. 673 ◽  
Author(s):  
MS Allen ◽  
AM Becker ◽  
RW Rickards
Keyword(s):  
Biological Activity ◽  
Antifungal Activity ◽  
Conjugated Diene ◽  
Methyl Derivative ◽  
Methyl Group ◽  
Diene System

The antibiotic responsible for the high antiyeast and antifungal activity of a streptomycete fermentation is shown to be the 9-methyl derivative (1) of streptimidone (2). The conjugated diene system in (1) is assigned the 6E,8Z stereochemistry. Evidence is presented for the biogenetic origin of the 9-methyl group in this streptimidone homologue, and its antifungal activity is compared with that of streptimidone and other fungicides.

scholarly journals Synthesis and biological activity of some 6.ALPHA.-formamido penicillins modified in the 2.BETA.-methyl group.

1990 ◽  
Vol 43 (8) ◽  
pp. 1042-1044 ◽  
Author(s):  
DAVID F. CORBETT ◽  
COLIN H. FRYDRYCH ◽  
ROBERT SOUTHGATE ◽  
MICHAEL J. BASKER
Keyword(s):  
Biological Activity ◽  
Methyl Group

Chiral synthesis of (+)-8′-demethyl abscisic acid

1996 ◽  
Vol 74 (10) ◽  
pp. 1836-1843 ◽  
Author(s):  
Patricia A. Rose ◽  
Bo Lei ◽  
Angela C. Shaw ◽  
Suzanne R. Abrams ◽  
M. K. Walker-Simmons ◽  
...  
Keyword(s):  
Biological Activity ◽  
Abscisic Acid ◽  
Enantioselective Synthesis ◽  
Phenol Oxidation ◽  
Germination Inhibition ◽  
Embryo Germination ◽  
Chiral Synthesis ◽  
Wheat Embryo ◽  
Methyl Group ◽  
Key Words Abscisic Acid

An enantioselective synthesis of (+)-8′-demethyl ABA (2) is described. The chiral intermediate 7 was prepared by yeast reduction of a substituted monoprotected cyclohexa-2,5-dien-1,4-dione (9) synthesized through a phenol oxidation. The scope and limitations of the phenol oxidation is described. 8′-Demethyl ABA shows ABA-like activity in wheat embryo germination inhibition, showing that the 8′-methyl group is not essential for biological activity. Key words: abscisic acid, phenol oxidation, yeast reduction.

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