Design, synthesis, and docking studies of new 1,3,4-thiadiazole-2-thione derivatives with carbonic anhydrase inhibitory activity. 2007

Mohammed K Abdel-Hamid, and Atef A Abdel-Hafez, and Nawal A El-Koussi, and Nadia M Mahfouz, and Alessio Innocenti, and Claudiu T Supuran
Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt. mohkam78@yahoo.com

A new series of 1,3,4-thiadiazole-2-thione derivatives have been prepared and assayed for the inhibition of three physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isozymes, the cytosolic human isozymes I and II, and the transmembrane, tumor-associated hCA IX. Against hCA I the investigated thiones, showed inhibition constants in the range of 2.55-222 microM, against hCA II in the range of 2.0-433 microM, and against hCA IX in the range of 1.25-148 microM. Compound 5c, 4-(4,5-dihydro-5-thioxo-1,3,4-thiadiazol-2-yl)-1-(5-nitro-2-oxoindolin-3-ylidene)semicarbazide showed interesting inhibition of the tumor-associated hCA IX with K(I) value of 1.25 microM, being the first non-sulfonamide type inhibitor of such activity. This result is rather important taking into consideration the known antitumor activity of thiones. In addition, docking of the tested compounds into CA II active site was performed in order to predict the affinity and orientation of these compounds at the isozyme active site. The results showed similar orientation of the target compounds at CA II active site compared with reported sulfonamide type CAIs with the thione group acting as a zinc-binding moiety.

UI MeSH Term Description Entries
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D002257 Carbonic Anhydrase Inhibitors A class of compounds that reduces the secretion of H+ ions by the proximal kidney tubule through inhibition of CARBONIC ANHYDRASES. Carbonate Dehydratase Inhibitor,Carbonate Dehydratase Inhibitors,Carbonic Anhydrase Inhibitor,Carboxyanhydrase Inhibitor,Carboxyanhydrase Inhibitors,Anhydrase Inhibitor, Carbonic,Dehydratase Inhibitor, Carbonate,Inhibitor, Carbonate Dehydratase,Inhibitor, Carbonic Anhydrase,Inhibitor, Carboxyanhydrase,Inhibitors, Carbonate Dehydratase,Inhibitors, Carbonic Anhydrase,Inhibitors, Carboxyanhydrase
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013830 Thiadiazoles Heterocyclic compounds composed of a five-membered heterocyclic ring which contains one sulfur and two nitrogen atoms. Thiadiazole
D013871 Thiones Sulfur-containing compounds also known as thioketones of general formula R2C Thioketone,Thione,Thioketones
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D017434 Protein Structure, Tertiary The level of protein structure in which combinations of secondary protein structures (ALPHA HELICES; BETA SHEETS; loop regions, and AMINO ACID MOTIFS) pack together to form folded shapes. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Tertiary Protein Structure,Protein Structures, Tertiary,Tertiary Protein Structures

Related Publications

Mohammed K Abdel-Hamid, and Atef A Abdel-Hafez, and Nawal A El-Koussi, and Nadia M Mahfouz, and Alessio Innocenti, and Claudiu T Supuran
July 2017, Bioorganic & medicinal chemistry,
Mohammed K Abdel-Hamid, and Atef A Abdel-Hafez, and Nawal A El-Koussi, and Nadia M Mahfouz, and Alessio Innocenti, and Claudiu T Supuran
February 2023, Molecular diversity,
Mohammed K Abdel-Hamid, and Atef A Abdel-Hafez, and Nawal A El-Koussi, and Nadia M Mahfouz, and Alessio Innocenti, and Claudiu T Supuran
December 2008, Journal of enzyme inhibition and medicinal chemistry,
Mohammed K Abdel-Hamid, and Atef A Abdel-Hafez, and Nawal A El-Koussi, and Nadia M Mahfouz, and Alessio Innocenti, and Claudiu T Supuran
May 2009, Bioorganic & medicinal chemistry,
Mohammed K Abdel-Hamid, and Atef A Abdel-Hafez, and Nawal A El-Koussi, and Nadia M Mahfouz, and Alessio Innocenti, and Claudiu T Supuran
January 1995, Bollettino chimico farmaceutico,
Mohammed K Abdel-Hamid, and Atef A Abdel-Hafez, and Nawal A El-Koussi, and Nadia M Mahfouz, and Alessio Innocenti, and Claudiu T Supuran
January 2019, PeerJ,
Mohammed K Abdel-Hamid, and Atef A Abdel-Hafez, and Nawal A El-Koussi, and Nadia M Mahfouz, and Alessio Innocenti, and Claudiu T Supuran
July 2021, Archiv der Pharmazie,
Mohammed K Abdel-Hamid, and Atef A Abdel-Hafez, and Nawal A El-Koussi, and Nadia M Mahfouz, and Alessio Innocenti, and Claudiu T Supuran
January 1998, Metal-based drugs,
Mohammed K Abdel-Hamid, and Atef A Abdel-Hafez, and Nawal A El-Koussi, and Nadia M Mahfouz, and Alessio Innocenti, and Claudiu T Supuran
April 2011, Journal of enzyme inhibition and medicinal chemistry,
Mohammed K Abdel-Hamid, and Atef A Abdel-Hafez, and Nawal A El-Koussi, and Nadia M Mahfouz, and Alessio Innocenti, and Claudiu T Supuran
January 2024, Molecules (Basel, Switzerland),
Copied contents to your clipboard!