Structure-Aided Computational Design of Triazole-Based Targeted Covalent Inhibitors of Cruzipain.

ABSTRACT: Cruzipain (CZP), the major cysteine protease present in T. cruzi, the ethiological agent of Chagas disease, has attracted particular attention as a therapeutic target for the development of targeted covalent inhibitors (TCI). The vast chemical space associated with the enormous molecular diversity feasible to explore by means of modern synthetic approaches allows the design of CZP inhibitors capable of exhibiting not only an efficient enzyme inhibition but also an adequate translation to anti-T. cruzi activity. In this work, a computer-aided design strategy was developed to combinatorially construct and screen large libraries of 1,4-disubstituted 1,2,3-triazole analogues, further identifying a selected set of candidates for advancement towards synthetic and biological activit

SUBMITTER: Cerutti JP 

PROVIDER: S-EPMC11396839 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature