Design and synthesis of amino acid derivatives of substituted benzimidazoles and pyrazoles as Sirt1 inhibitors.

ABSTRACT: Owing to its presence in several biological processes, Sirt1 acts as a potential therapeutic target for many diseases. Here, we report the structure-based designing and synthesis of two distinct series of novel Sirt1 inhibitors, benzimidazole mono-peptides and amino-acid derived 5-pyrazolyl methylidene rhodanine carboxylic acid. The compounds were evaluated for in vitro enzyme-based and cell-based Sirt1 inhibition assay, and cytotoxic-activity in both liver and breast cancer cells. The tryptophan conjugates i.e.13h (IC₅₀ = 0.66 μM, ΔG _bind = -1.1 kcal mol^-1) and 7d (IC₅₀ = 0.77 μM, ΔG _bind = -4.4 kcal mol^-1) demonstrated the maximum efficacy to inhibit Sirt1. The MD simulation unveiled that electr

SUBMITTER: Purushotham N 

PROVIDER: S-EPMC8981170 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature