Development of potential cathepsin B inhibitors: Synthesis of new bithiazole derivatives, in vitro studies supported with theoretical docking studies.

Cysteine cathepsins play a crucial role in cancer, inflammation, and the regulation of degenerative processes such as apoptosis, making them significant targets in drug development. In this study, we designed, synthesized, and characterized sixteen novel bi-thiazole derivatives, confirmed by 1H NMR, 13C NMR, HRMS, and X-ray analysis, which demonstrated significant therapeutic potential as inhibitors of cathepsin B. The synthesized thiazoles showed % inhibition in the range of 59.11-77.32, out of which bis-methoxyphenyl derivative 8k showed the highest inhibition of 77.32 % with IC50 and ki values of 1.04 nM and 0.52 nM, respectively. Methoxy-containing derivatives 8c, 8g, 8i, 8j, 8l, and 8o showed improved inhibition over methyl and chloro. In silico studies of the new bis-thiazole compounds at cathepsin B active sites supported the in vitro findings, indicating that the synthesized bis-thiazole esters are promising therapeutic candidates for conditions involving elevated cathepsin B levels.

Recent advances in the synthesis of cholesterol-based triazoles and their biological applications.

Double-headed warheads focusing on the pharmacological aspects as well as membrane permeability can contribute a lot to medicinal chemistry. Over the past few decades, a lot of research has been conducted on steroid-heterocycle conjugates as possible therapeutic agents against a variety of disorders. In the second half of the 20th century, successful research was conducted on cholesterol-based heterocyclic moieties. Keeping in view the biological significance of various triazoles, research on fusion with cholesterol has emerged. This review has been designed to explore the chemistry of cholesterol-based triazoles for the duration from 2010 to 2023 and their significance in medicinal chemistry.