Utilization of transition metal fluoride-based solid support catalysts for the synthesis of sulfonamides: carbonic anhydrase inhibitory activity and in silico study.

The applications of solid support catalysts in catalyzing organic reactions are well-evident. In the present study, we explored a transition metal fluoride (FeF3) adsorbed on molecular sieves (4 Å) as a solid support catalyst for the preparation of sulfonamides 3a-3o. The solid support catalyst was characterized via X-ray diffraction and AFM analysis. The catalyst was further explored for the synthesis of indoles 6a-h, 1H-tetrazoles and 1,4-dihydropyridines. The sulfonamides prepared herein were investigated for their potential to inhibit carbonic anhydrase (hCA II, hCA IX and hCA XII). All compounds were found to be active inhibitors with IC50 values in the low micromolar range. Some compounds were even found to be highly selective inhibitors. Compound 3i only inhibited hCA II (IC50 = 2.76 ± 1.1 µM) and had <27% inhibition against hCA IX and hCA XII. Similarly, 3e (IC50 = 0.63 ± 0.14 µM) only inhibited hCA XII and showed <31% inhibition against hCA II and hCA IX. Molecular docking studies were carried out to rationalize the ligand-binding site interactions. Given the lack of selective CA inhibitors, compounds 3e and 3i can provide significant leads for the further development of highly selective CA inhibitors.

Natural products embedded crown ethers as potent insulin secretory agents.

Natural products embedded crown ethers were prepared by utilizing bioactive natural products including chrysin, tetrahydroisoquinoline (THIQ), and biochanin-A. The prepared crown ether scaffolds were evaluated and compared with their natural product precursors for insulin secretory activity on isolated mice islets and for their fluorescent properties. All the crown adducts were found more active as compared to their natural product precursors. Bischrysin 32-crown-10 (6d), THIQ 15-Crown-5 (6a) and chrysin 16-crown-5 (6c) showed mild, moderate and strong insulin secretory activity, respectively when compared with the standard drug tolbutamide (TB). Particularly crown derivative 6c showed strong activity (31.10 ng/islet/h) that is almost two (02) fold higher than that of standard drug TB (16.82 ng/islet/h). To the best of our knowledge crown ethers based antidiabetic study is being reported for the first time in literature through this work. Furthermore, fluorescence study showed the significant increase in absorption and emission maximum (hypsochromic effect) in crown structures when compared with their natural product precursors. Present optimistic results obtained from this study may be a guided template for developing new effective insulin secretory agents.