scholarly journals Synthesis and Inhibition Activity Study of Triazinyl-Substituted Amino(alkyl)-benzenesulfonamide Conjugates with Polar and Hydrophobic Amino Acids as Inhibitors of Human Carbonic Anhydrases I, II, IV, IX, and XII

2021 ◽  
Vol 22 (20) ◽  
pp. 11283
Author(s):  
Mária Bodnár Mikulová ◽  
Dáša Kružlicová ◽  
Daniel Pecher ◽  
Andrea Petreni ◽  
Claudiu T. Supuran ◽  
...  
Keyword(s):  
Amino Acids ◽  
Side Chain ◽  
Carbonic Anhydrases ◽  
Inhibition Activity ◽  
Short Reaction Time ◽  
High Affinity ◽  
Hydrophobic Amino Acids ◽  
In Vitro Inhibition ◽  
Inhibition Studies

Primary sulfonamide derivatives with various heterocycles represent the most widespread group of potential human carbonic anhydrase (hCA) inhibitors with high affinity and selectivity towards specific isozymes from the hCA family. In this work, new 4-aminomethyl- and aminoethyl-benzenesulfonamide derivatives with 1,3,5-triazine disubstituted with a pair of identical amino acids, possessing a polar (Ser, Thr, Asn, Gln) and non-polar (Ala, Tyr, Trp) side chain, have been synthesized. The optimized synthetic, purification, and isolation procedures provided several pronounced benefits such as a short reaction time (in sodium bicarbonate aqueous medium), satisfactory yields for the majority of new products (20.6–91.8%, average 60.4%), an effective, well defined semi-preparative RP-C18 liquid chromatography (LC) isolation of desired products with a high purity (>97%), as well as preservation of green chemistry principles. These newly synthesized conjugates, plus their 4-aminobenzenesulfonamide analogues prepared previously, have been investigated in in vitro inhibition studies towards hCA I, II, IV and tumor-associated isozymes IX and XII. The experimental results revealed the strongest inhibition of hCA XII with low nanomolar inhibitory constants (Kis) for the derivatives with amino acids possessing non-polar side chains (7.5–9.6 nM). Various derivatives were also promising for some other isozymes.

scholarly journals Mycobacterium tuberculosis β-Carbonic Anhydrases: Novel Targets for Developing Antituberculosis Drugs

2019 ◽  
Vol 20 (20) ◽  
pp. 5153 ◽  
Author(s):  
Aspatwar ◽  
Kairys ◽  
Rala ◽  
Parikka ◽  
Bozdag ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
In Vivo Studies ◽  
Close Relative ◽  
Carbonic Anhydrases ◽  
In Vitro Inhibition ◽  
Inhibition Studies

The genome of Mycobacterium tuberculosis (Mtb) encodes three β-carbonic anhydrases (CAs, EC 4.2.1.1) that are crucial for the life cycle of the bacterium. The Mtb β-CAs have been cloned and characterized, and the catalytic activities of the enzymes have been studied. The crystal structures of two of the enzymes have been resolved. In vitro inhibition studies have been conducted using different classes of carbonic anhydrase inhibitors (CAIs). In vivo inhibition studies of pathogenic bacteria containing β-CAs showed that β-CA inhibitors effectively inhibited the growth of pathogenic bacteria. The in vitro and in vivo studies clearly demonstrated that β-CAs of not only mycobacterial species, but also other pathogenic bacteria, can be targeted for developing novel antimycobacterial agents for treating tuberculosis and other microbial infections that are resistant to existing drugs. In this review, we present the molecular and structural data on three β-CAs of Mtb that will give us better insights into the roles of these enzymes in pathogenic bacterial species. We also present data from both in vitro inhibition studies using different classes of chemical compounds and in vivo inhibition studies focusing on M. marinum, a model organism and close relative of Mtb.

13C nuclear magnetic resonance study of cyclodipeptides containing 13C enriched hydrophobic amino acids

1980 ◽  
Vol 45 (2) ◽  
pp. 482-490 ◽  
Author(s):  
Jaroslav Vičar ◽  
François Piriou ◽  
Pierre Fromageot ◽  
Karel Bláha ◽  
Serge Fermandjian
Keyword(s):  
Amino Acids ◽  
Nuclear Magnetic Resonance ◽  
Nuclear Magnetic Resonance Study ◽  
Coupling Constants ◽  
Side Chain ◽  
Amino Acid Residues ◽  
Magnetic Resonance Study ◽  
Side Chain Conformation ◽  
13C Nuclear Magnetic Resonance ◽  
Hydrophobic Amino Acids

The diastereoisomeric pairs of cyclodipeptides cis- and trans-cyclo(Ala-Ala), cyclo(Ala-Phe), cyclo(Val-Val) and cyclo(Leu-Leu) containing 85% 13C enriched amino-acid residues were synthesized and their 13C-13C coupling constants were measured. The combination of 13C-13C and 1H-1H coupling constants enabled to estimate unequivocally the side chain conformation of the valine and leucine residues.

scholarly journals Binding of peptides that are specified by complementary RNAs

1986 ◽  
Vol 234 (3) ◽  
pp. 679-683 ◽  
Author(s):  
J E Blalock ◽  
K L Bost
Keyword(s):  
Amino Acids ◽  
Genetic Code ◽  
High Affinity ◽  
Interesting Pattern ◽  
Hydrophobic Amino Acids ◽  
Complementary Rnas

An interesting pattern in the genetic code was reported previously [Blalock & Smith (1984) Biochem. Biophys. Res. Commun. 121, 203-207]. In the 5′-to-3′ direction, codons for hydrophilic and hydrophobic amino acids are generally complemented by codons for hydrophobic and hydrophilic amino acids respectively. The average tendency of codons for ‘unchanged’ (slightly hydrophilic) amino acids was to be complemented by codons for ‘unchanged’ amino acids. We now show that the same pattern results when the complementary codon is read in the 3′-to-5′ direction. This pattern is further shown to result in the interaction of peptides specified by complementary RNAs regardless of whether the amino acids are assigned in the 5′-to-3′ or the 3′-to-5′ direction. Here we demonstrate that peptides specified by complementary RNAs bind to each other with specificity and high affinity.

In vitro inhibition of cytosolic carbonic anhydrases I and II by some new dihydroxycoumarin compounds

2008 ◽  
Vol 23 (1) ◽  
pp. 32-36 ◽  
Author(s):  
Ismet Basaran ◽  
Selma Sinan ◽  
Umit Cakir ◽  
Mustafa Bulut ◽  
Oktay Arslan ◽  
...  
Keyword(s):  
Carbonic Anhydrases ◽  
In Vitro Inhibition

On the in vitro inhibition of catalase by amino acids

1957 ◽  
Vol 23 ◽  
pp. 362-366 ◽  
Author(s):  
G. Ceriotti ◽  
L. Spandrio ◽  
E. Berti
Keyword(s):  
Amino Acids ◽  
In Vitro Inhibition
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