Inhibition of carbonic anhydrase isoforms I, II, IX and XII with Schiff's bases incorporating iminoureido moieties.
A series of new Schiff's bases was obtained from the sulfanilamide semicarbazone (4-aminosulfonylphenyl semicarbazide) and aromatic/heterocyclic aldehydes. The new compounds were designed to incorporate moieties known to induce effective inhibitory activity against carbonic anhydrase (CA, EC 4.2.1.1) isoforms involved in crucial physiologic or pathologic processes such as the cytosolic CA I and II or the transmembrane, tumor-associated CA IX and XII: the compounds were medium potency - weak CA I inhibitors, highly effective, low nanomolar CA II inhibitors, but few of them inhibited effectively CA IX and XII. This may probably due to the long spacer between the sulfamoylphenyl and imine fragments of the molecules, which probably induces a highly flexible conformation of the inhibitor bound to the active site of the enzyme, with destabilizing effects for the adduct. The detailed structure activity relationship for this class of inhibitors is discussed.
a Department of Pharmaceutical Chemistry , Bharati Vidyapeeth's College of Pharmacy , Navi Mumbai , India .
Namrata
N
Singasane
b Department of Pharmaceutical Chemistry , SPP School of Pharmacy and Technology Management, SVKM's NMIMS , Mumbai , India .
Prashant S
PS
Kharkar
c Laboratorio di Chimica Bioinorganica , Università degli Studi di Firenze , Sesto Fiorentino (Firenze) , Italy , and.|d Neurofarba Department , Sezione di Scienze Farmaceutiche , Sesto Fiorentino (Firenze) , Italy.
Mariangela
M
Ceruso
c Laboratorio di Chimica Bioinorganica , Università degli Studi di Firenze , Sesto Fiorentino (Firenze) , Italy , and.|d Neurofarba Department , Sezione di Scienze Farmaceutiche , Sesto Fiorentino (Firenze) , Italy.
Claudiu T
CT
Supuran
a Department of Pharmaceutical Chemistry , Bharati Vidyapeeth's College of Pharmacy , Navi Mumbai , India .
Mrunmayee P
MP
Toraskar
D000951:Antigens, Neoplasm / Q000378:metabolism; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007097:Imines / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D012545:Schiff Bases / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000951:Antigens, Neoplasm; D002257:Carbonic Anhydrase Inhibitors; D007097:Imines; D012545:Schiff Bases; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; C483903:CA13 protein, human; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
Carbonic anhydrase; Schiff’s base; cytosolic/tumor-associated enzymes; isoform-selective inhibitor; sulfonamide