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.

Anticancer and Radiosensitization Efficacy of Nanocomposite Withania somnifera Extract in Mice Bearing Tumor Cells.

The objective of the present study was to evaluate the anticancer and radio-sensitizing efficacy of a Withania somnifera extract/Gadolinium III oxide nanocomposite (WSGNC) in mice. WSGNC was injected to solid Ehrlich carcinoma-bearing mice via i.p. (227 mg/kg body weight) 3 times/week during 3 weeks. Irradiation was performed by whole body fractionated exposure to 6Gy, applied in 3 doses of 2 Gy/week over 3 weeks. Biochemical analyses as well as DNA fragmentation were performed. Treatment of solid Ehrlich carcinoma bearing mice with WSGNC combined with γ-radiation led to a significant decrease in the tumor size and weight associated with a significant decrease in mitochondrial enzyme activities, GSH content and SOD activity as well as a significant increase in caspase-3 activity, MDA concentration and DNA fragmentation in cancer tissues. Combined treatment of WSGNC and low dose of γ-radiation showed great amelioration in lipid peroxidation and antioxidant status (GSH content and SOD activity) in liver tissues in animals bearing tumors. It is concluded that WSGNC can be considered as a radio-sensitizer and anticancer modulator, suggesting a possible role in reducing the radiation exposure dose during radiotherapy.