Click chemistry approaches for developing carbonic anhydrase inhibitors and their applications

Abstract

Click chemistry reactions constitute an important and relatively new approach in the medicinal chemistry toolbox and offer substantial advantages to medicinal chemists in terms of overcoming the limitations of facile chemical synthesis, increased throughput, yields and improved quality of compound libraries. Over the last two decades, click chemistry has been widely used in different aspects of carbonic anhydrase (CA, EC 4.2.1.1) modulators drug design. This review provides an overview of the general principles and applications of click chemistry in CA-related research, including the design of selective CA inhibitors (CAIs), their applications against several diseases such as innovative anticancer and anti-infective agents, fluorescent and radiopharmaceutical probes as new theranostic agents, as well as their application in protein labelling.

6-Substituted Triazolyl Benzoxaboroles as Selective Carbonic Anhydrase Inhibitors: In Silico Design, Synthesis, and X-ray Crystallography

“…Indeed, the 1,2,3-triazole ring is an amide bioisostere endowed with a moderate dipole character, hydrogen bonding capability, stability in the in vivo environment, and an aromatic character that may allow π-stacking interactions with the enzyme counterparts. 30 We report herein the first 1,2,3-triazolylsubstituted benzoxaboroles as hCA inhibitors. In detail, a molecular modeling method was used to predict the most favorable positions of the aromatic scaffold in terms of ligand− target interactions to append the triazole spacer.…”

“…The copper-catalyzed azide–alkyne cycloaddition (CuAAC) has gained a prominent role in medicinal chemistry, being a versatile synthetic tool to generate 1,4-disubstituted-1,2,3-triazoles, as biologically uncleavable linkers between molecular fragments or as moieties to actively contribute to the ligand–target interactions. Indeed, the 1,2,3-triazole ring is an amide bioisostere endowed with a moderate dipole character, hydrogen bonding capability, stability in the in vivo environment, and an aromatic character that may allow π-stacking interactions with the enzyme counterparts . We report herein the first 1,2,3-triazolyl-substituted benzoxaboroles as hCA inhibitors.…”

Click-derived multifunctional metal complexes for diverse applications

“…It involves the achievement of new molecular properties based on necessity, which can be brought about by merging two molecular entities. [17][18][19] Many chemical methods exist but there are great levels of difficulty that require certain expertise. Since 2001, with codification by Professor K. Barry Sharpless, Click chemistry is considered one of the most powerful toolboxes for synthetic chemists.…”

Lead Optimization of BIBR1591 To Improve Its Telomerase Inhibitory Activity: Design and Synthesis of Novel Four Chemical Series with In Silico, In Vitro, and In Vivo Preclinical Assessments

“…Interestingly, telomerase enzyme expression and activity were found to be absent in somatic cells while highly expressed in 85–90% of tumor cell lines, indicating its involvement in cancer development. Thus, the importance of discovering novel telomerase inhibitors as potentially selective anticancer agents is highlighted. − …”