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 |
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Authors: | Salwa M I Morsy Abdelfattah M Badawi Alessandro Cecchi Andrea Scozzafava |
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Institution: | 1. Applied Surfactant Laboratory, Egyptian Petroleum Research Institute, Nasr City, Cairo, Egypt;2. Laboratorio di Chimica Bioinorganica, Università degli Studi di Firenze, Polo Scientifico, Rm. 188, Via della Lastruccia 350019, Sesto Fiorentino (Florence), Italy |
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Abstract: | 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 GI50 values in the range of 0.74–10.0 μg/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. |
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Keywords: | Carbonic anhydrase CA-IX inhibitors cytotoxic cancer cell lines HCT 116 H460 MCF-7 |
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