Uracil derivatives as HIV-1 capsid protein inhibitors: design, in silico, in vitro and cytotoxicity studies.

ABSTRACT: A series of novel uracil derivatives such as bispyrimidine dione and tetrapyrimidine dione derivatives were designed based on the existing four-point pharmacophore model as effective HIV capsid protein inhibitors. The compounds were initially docked with an HIV capsid protein monomer to rationalize the ideas of design and to find the potential binding modes. The successful design and computational studies led to the synthesis of bispyrimidine dione and tetrapyrimidine dione derivatives from uracil and aromatic aldehydes in the presence of HCl using novel methodology. The in vitro evaluation in HIV p24 assay revealed five potential uracil derivatives with IC₅₀ values ranging from 191.5 μg ml^-1 to 62.5 μg ml^-1. The meta-chloro substituted uracil

SUBMITTER: Ramesh D 

PROVIDER: S-EPMC9190787 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature