Pyridinium derivatives of 3-aminobenzenesulfonamide are nanomolar-potent inhibitors of tumor-expressed carbonic anhydrase isozymes CA IX and CA XII

International audienceBuilding on the conclusions of previous inhibition studies with pyridinium-benzenesulfonamides from our team and on the X-ray crystal structure of the lead compound identified, a series of 24 pyridinium derivatives of 3-aminobenzenesulfonamide was synthesized and investigated for carbonic anhydrase inhibition. The new pyridinium-sulfonamides were evaluated as inhibitors of four human carbonic anhydrase (CA, EC 4.2.1.1) isoforms, namely CA I, CA II (cytosolic), CA IX and XII (transmembrane, tumor-associated forms). Excellent inhibitory activity in the nanomolar range was observed against CA IX with most of these sulfonamides, and against CA XII (nanomolar/sub-nanomolar) with some of the new compounds. These sulfonamides were generally potent inhibitors of CA II and CA I too. Docking studies revealed a preference of these compounds to bind the P1 hydrophobic site of CAs, supporting the observed inhibition profile. The salt-like nature of these positively charged sulfonamides can further focus the inhibitory ability on membrane-bound CA IX and CA XII and could efficiently decrease the viability of three human carcinomas under hypoxic conditions where these isozymes are over-expressed, thus recommending the new compounds as potential diagnostic tools or therapeutic agents

Pyridinium derivatives of 3-aminobenzenesulfonamide are nanomolar-potent inhibitors of tumor-expressed carbonic anhydrase isozymes CA IX and CA XII

Building on the conclusions of previous inhibition studies with pyridinium-benzenesulfonamides from our team and on the X-ray crystal structure of the lead compound identified, a series of 24 pyridinium derivatives of 3-aminobenzenesulfonamide was synthesized and investigated for carbonic anhydrase inhibition. The new pyridinium-sulfonamides were evaluated as inhibitors of four human carbonic anhydrase (CA, EC 4.2.1.1) isoforms, namely CA I, CA II (cytosolic), CA IX and XII (transmembrane, tumor-associated forms). Excellent inhibitory activity in the nanomolar range was observed against CA IX with most of these sulfonamides, and against CA XII (nanomolar/sub-nanomolar) with some of the new compounds. These sulfonamides were generally potent inhibitors of CA II and CA I too. Docking studies revealed a preference of these compounds to bind the P1 hydrophobic site of CAs, supporting the observed inhibition profile. The salt-like nature of these positively charged sulfonamides can further focus the inhibitory ability on membrane-bound CA IX and CA XII and could efficiently decrease the viability of three human carcinomas under hypoxic conditions where these isozymes are overexpressed, thus recommending the new compounds as potential diagnostic tools or therapeutic agents

Synthesis, characterization, and applications of hemicellulose based eco-friendly polymer composites

This book presents emerging economical and environmentally friendly polymer composites that are free of the side effects observed in traditional composites. It focuses on eco-friendly composite materials using granulated cork, a by-product of the cork industry; cellulose pulp from the recycling of paper residues; hemp fibers; and a range of other environmentally friendly materials procured from various sources. The book presents the manufacturing methods, properties and characterization techniques of these eco-friendly composites. The respective chapters address classical and recent aspects of eco-friendly polymer composites and their chemistry, along with practical applications in the biomedical, pharmaceutical, automotive and other sectors. Topics addressed include the fundamentals, processing, properties, practicality, drawbacks and advantages of eco-friendly polymer composites. Featuring contributions by experts in the field with a variety of backgrounds and specialties, the book will appeal to researchers and students in the fields of materials science and environmental science. Moreover, it fills the gap between research work in the laboratory and practical applications in related industries. © Springer Nature Switzerland AG 2019