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

Abstract

The paper describes the design, synthesis, computational and biological validation of a series of novel uracil derivatives as effective HIV capsid protein inhibitors.

Uracil: A Pharmacophore with Diverse Biological Potential

“…Sakakibara et al [72] The synthesised compounds were tested for its anti-HIV-1 activity. [73] The results have shown that compound 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil 140 a exhibited significant activity against HIV-1 with an EC 50 value of 0.01 μM respectively.…”

“…The reaction involved the treatment of 6‐azido‐1‐(4‐nitrobenzyl) uracil 139 a and 6‐azido‐1‐(2‐nitrobenzyl)uracil 139 b derivatives using NaBH 4 in the presence of methanol and THF to yield diamino derivatives of type 140 a – b . The synthesised compounds were tested for its anti‐HIV‐1 activity [73] . The results have shown that compound 6‐amino‐3‐(3,5‐dimethylbenzyl)‐1‐(4‐aminobenzyl)uracil 140 a exhibited significant activity against HIV‐1 with an EC 50 value of 0.01 μM respectively.…”

Mandelic acid catalyzed one-pot pseudo three-component synthesis of various trisubstituted methane derivatives at room temperature

“…6 As an anti-neoplastic agent, uracil itself has been used in combination with tegafur (a chemotherapeutic prodrug of 5-fluorouracil) to treat various cancers, including breast, prostate, and liver cancer. 7 Very recently, Ramesh et al 8 synthesized a series of bis-uracil substituted aryl methylene derivatives. In vitro study of the synthesized compounds in HIV p24 assay revealed that five compounds, shown in Figure 5, possess promising HIV-1 capsid protein inhibitory efficacy.…”