New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators

A series of histamine (HST)-related compounds were synthesized and tested for their activating properties on five physiologically relevant human Carbonic Anhydrase (hCA) isoforms (I, II, Va, VII and XIII). The imidazole ring of HST was replaced with different 5-membered heterocycles and the length of the aliphatic chain was varied. For the most interesting compounds some modifications on the terminal amino group were also performed. The most sensitive isoform to activation was hCA I (KA values in the low micromolar range), but surprisingly none of the new compounds displayed activity on hCA II. Some derivatives (1, 3a and 22) displayed an interesting selectivity for activating hCA I over hCA II, Va, VII and XIII.

Download Full-text

Thermodynamics of binding of the carbon dioxide-competitive inhibitor imidazole and related compounds to human carbonic anhydrase I: an isothermal titration calorimetry approach to studying weak binding by displacement with strong inhibitors

Biochemistry ◽

10.1021/bi00063a017 ◽

1993 ◽

Vol 32 (12) ◽

pp. 3058-3066 ◽

Cited By ~ 20

Author(s):

Raja G. Khalifah ◽

Fengli Zhang ◽

James S. Parr ◽

Elizabeth S. Rowe

Keyword(s):

Carbon Dioxide ◽

Carbonic Anhydrase ◽

Isothermal Titration Calorimetry ◽

Competitive Inhibitor ◽

Titration Calorimetry ◽

Carbonic Anhydrase I ◽

Weak Binding ◽

Human Carbonic Anhydrase ◽

Related Compounds

Download Full-text

Synthesis and Human Carbonic Anhydrase I, II, IX, and XII Inhibition Studies of Sulphonamides Incorporating Mono-, Bi- and Tricyclic Imide Moieties

Pharmaceuticals ◽

10.3390/ph14070693 ◽

2021 ◽

Vol 14 (7) ◽

pp. 693

Author(s):

Kalyan K. Sethi ◽

KM Abha Mishra ◽

Saurabh M. Verma ◽

Daniela Vullo ◽

Fabrizio Carta ◽

...

Keyword(s):

Molecular Docking ◽

Carbonic Anhydrase ◽

Docking Studies ◽

Carbonic Anhydrases ◽

Molecular Docking Studies ◽

Structure Activity Relationships ◽

Structure Activity ◽

Carbonic Anhydrase I ◽

Human Carbonic Anhydrase ◽

Inhibition Studies

New derivatives were synthesised by reaction of amino-containing aromatic sulphonamides with mono-, bi-, and tricyclic anhydrides. These sulphonamides were investigated as human carbonic anhydrases (hCAs, EC 4.2.1.1) I, II, IX, and XII inhibitors. hCA I was inhibited with inhibition constants (Kis) ranging from 49 to >10,000 nM. The physiologically dominant hCA II was significantly inhibited by most of the sulphonamide with the Kis ranging between 2.4 and 4515 nM. hCA IX and hCA XII were inhibited by these sulphonamides in the range of 9.7 to 7766 nM and 14 to 316 nM, respectively. The structure–activity relationships (SAR) are rationalised with the help of molecular docking studies.

Download Full-text

Crystal analysis of aromatic sulfonamide binding to native and (Zn)2 adduct of human carbonic anhydrase I Michigan 1

Inorganica Chimica Acta ◽

10.1016/s0020-1693(02)00959-3 ◽

2002 ◽

Vol 339 ◽

pp. 135-144 ◽

Cited By ~ 6

Author(s):

Marta Ferraroni ◽

Fabrizio Briganti ◽

W.Richard Chegwidden ◽

Claudiu T. Supuran ◽

Andrea Scozzafava

Keyword(s):

Carbonic Anhydrase ◽

Carbonic Anhydrase I ◽

Human Carbonic Anhydrase ◽

Aromatic Sulfonamide

Download Full-text

A simple enzyme-linked immunoassay of human carbonic anhydrase I for the study of developing erythroid cells

Clinica Chimica Acta ◽

10.1016/0009-8981(90)90018-n ◽

1990 ◽

Vol 191 (3) ◽

pp. 169-174 ◽

Cited By ~ 1

Author(s):

Takahito Kondo ◽

Kazuhiro Murakami ◽

Hiroshi Isobe ◽

Naoyuki Taniguchi ◽

Yoshikazu Kawakami

Keyword(s):

Carbonic Anhydrase ◽

Erythroid Cells ◽

Carbonic Anhydrase I ◽

Human Carbonic Anhydrase

Download Full-text

Photogeneration of Superoxide Anion upon Illumination of Purines and Pyrimidines in the Presence of Riboflavin: Structure-activity Relationships

Journal of Food Protection ◽

10.4315/0362-028x-43.1.19 ◽

1980 ◽

Vol 43 (1) ◽

pp. 19-20 ◽

Cited By ~ 3

Author(s):

MALGORZATA KORYCKA-DAHL ◽

THOMAS RICHARDSON

Keyword(s):

Superoxide Dismutase ◽

Superoxide Anion ◽

Orotic Acid ◽

Imidazole Ring ◽

Fluorescent Light ◽

Carboxyl Group ◽

Amino Group ◽

Structure Activity ◽

Related Compounds ◽

Purines And Pyrimidines

Photogenerated superoxide anion might be involved in the oxidative deterioration of foods. For this reason, purines, pyrimidines and related compounds were illuminated with fluorescent light in the presence of riboflavin to examine their capacity to photogenerate superoxide anion (measured from suppression of its reduction of nitro blue tetrazolium by superoxide dismutase). Superoxide anion was photogenerated in the presence of guanine, xanthine, 6-thioguanine, thymine, uracil, 6-methyl uracil, orotic acid and 5- as well as 6-amino uracil but not in the presence of 24 other related compounds examined. Replacing the oxygen at the 6-position of guanine with sulfur or attachment of an amino group to the 5- or 6-carbon of uracil greatly increased superoxide anion generation as compared to guanine and uracil, respectively. The attachment of a carboxyl group at the 6-position of uracil augmented superoxide anion photogeneration to a much smaller extent and thymine and 6-methyl uracil did not yield any more superoxide anion than did uracil. In general, only those compounds which had an oxo group at the 6-position of purines or the 4-position of pyrimidines, and either an oxo or an amino group in the 2-position of either ring served as substrates for photogeneration of superoxide anion. Additionally, presence of purines and pyrimidines in an enol and/or amino form and an unsubstituted imidazole ring for purines were required for photogeneration of superoxide anion.

Download Full-text