Carbonic anhydrase inhibitors. Biphenylsulfonamides with inhibitory action towards the transmembrane, tumor-associated isozymes IX possess cytotoxic activity against human colon, lung and breast cancer cell lines.
Reaction of 4,4-biphenyl-disulfonyl chloride with aromatic/heterocyclic sulfonamides also incorporating a free amino group, such as 4-aminobenzenesulfonamide, 4-aminoethyl-benzenesulfonamide, 6-chloro-4-aminobenzene-1,3-disulfonamide or 5-amino-1,3,4-thiadiazole-2-sulfonamide afforded bis-sulfonamides which have been tested as inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4..2.1.1). The compounds were rather modest inhibitors of isozymes CA I and XII, but were more efficient as inhibitors of the cytosolic CA II and transmembrane, tumor-associated CA IX (inhibition constants in the range of 21-129 nM gainst hCA II, and 23-79 nM against hCA IX, respectively). The new bis-sulfonamides also showed inhibition of growth of several tumor cell lines (ex vivo), with GI(50) values in the range of 0.74-10.0 microg/mL against the human colon cancer cell line HCT116, the human lung cancer cell line H460 and the human breast cancer cell line MCF-7.
Morsy
Salwa M I
SM
Applied Surfactant Laboratory, Egyptian Petroleum Research Institute, Nasr City, Cairo, Egypt.
Badawi
Abdelfattah M
AM
Cecchi
Alessandro
A
Scozzafava
Andrea
A
Supuran
Claudiu T
CT
D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity*; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000633:toxicity*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism; D013449:Sulfonamides / Q000633:toxicity*
D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D002256:Carbonic Anhydrases