A decade of tail-approach based design of selective as well as potent tumor associated carbonic anhydrase inhibitors

• Published in: Bioorganic chemistry 2022-09, Vol.126, p.105920-105920, Article 105920
• Main Authors: Kumar, Amit, Siwach, Kiran, Supuran, Claudiu T., Sharma, Pawan K.
• Format: Article
• Language: English
• Subjects: Cancer; Carbonic anhydrase inhibitors; hCA IX; hCA XII; Potent inhibitors; Selective inhibitors; SLC-0111; Tail-approach
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2022.105920

[Display omitted] •Summative view of tail-approach based selective as well as potent hCA IX and XII inhibitors reported in the last decade.•Listing of the most promising molecules in terms of selectivity and potency from the available 181 research papers.•One stop solution to tailor the tail-approach based rational design of novel libraries of carbonic anhydrase inhibitors. Human carbonic anhydrase (hCA) isoforms hCA IX and hCA XII are well established anticancer drug targets and their selective inhibition is highly desired for the proper treatment of cancer. Lack of isoform-selectivity in current clinically used CA inhibitors (CAIs) is a major concern as it leads to undesired side effects, associated with off-target inhibition. Thus, there is need to explore alternative approaches for the design of isoform-selective inhibitors and the leading promising approach for the design of isoform-selective CAIs is “the tail-approach”. Virtually, most drug design studies in the last decade were done by considering the tail-approach reported in 1999. The past decade of 2010–2020 witnessed progressive maturation of this approach as a large number of CAIs have been designed and synthesised based on it, many of which turned out to be effective as well as selective hCA IX and hCA XII inhibitors. This review covers the past decade (2010–2020) research, considering selective as well as potent inhibitors of tumor associated isoforms, hCA IX and hCA XII, which include newer generation inhibitors containing sulfonamides or their bioisosteres, non-classical inhibitors (including carboxylic acid/ester, coumarin and sulfocoumarin classes) and various other novel classes of inhibitors belonging to newly identified chemotypes/scaffolds.