in silico Modeling of Curcumin Based Sulfonamides Inhibitors of the Human trans-Membrane Carbonic Anhydrase Isozyme, hCA IX by CoMSIA

Carbonic anhydrases, hCAs IX and XII are applied as the markers of progression of the disease in many oxygen deficient tumours and their specially manoeuvred inhibition is directly related to containing the growth of both primary tumours and tumour growth of secondary nature. Ligand-based quantitative structure-activity relationship (QSAR) studies were carried out on curcumin related, sulphonamide derivatives as inhibitors of human trans-membrane carbonic anhydrase isozyme, hCA IX by comparative molecular field similarity analysis (CoMSIA) implemented through the SYBYL package. The capacity of the model to predict coveted compound was evaluated using test set of three compounds. The best model created was found to be of choice as it showed a r2 value of 0.811 and a cross validated coefficient q2 value of 0.617 in tripos CoMSIA hydrophobic region. Results of the present study indicated that hydrophobic region factors play an important role in carbonic anhydrase hCA IX inhibition for compounds.

Sulfa Drugs as Inhibitors of Carbonic Anhydrase: New Targets for the Old Drugs

Sulfa drugs are well-known antibacterial agents containing N-substituted sulfonamide group on para position of aniline ring (NH2RSO2NHR′). In this study 2,4-dichloro-1,3,5-triazine derivatives of sulfa drugs, sulfamerazine (1b), sulfaquinoxaline (2b), sulfadiazine (3b), sulfadimidine (4b), and sulfachloropyrazine (5b) (1a–5a) were synthesized and characterized. Their carbonic anhydrase inhibition activity was evaluated against bovine cytosolic carbonic anhydrase isozyme II (bCA II). For the sake of comparison the CA inhibition activity of the parent sulfa drugs (1b–5b) was also evaluated. A significant increase in CA inhibition activity of sulfa drugs was observed upon substitution with 2,4-dichloro-1,3,5-triazine moiety. Molecular docking studies were carried out to highlight binding site interactions. ADME properties were calculated to evaluate drug likeness of the compounds.