Uracil Derivatives for Halogen-Bonded Cocrystals

Among non-covalent interactions, halogen bonding is emerging as a new powerful tool for supramolecular self-assembly. Here, along with a green and effective method, we report three new halogen-bonded cocrystals containing uracil derivatives and 1,2,4,5-tetrafluoro-3,6-diiodobenzene as X-bond donor coformer. These multicomponent solids were prepared both by solvent-drop grinding and solution methods and further characterized by powder and single-crystal X-ray diffraction, Fourier-transformed infrared spectroscopy, and thermal methods (TGA-DSC). In order to study the relative importance of hydrogen versus halogen bonds in the crystal packing, computational methods were applied.

A convenient synthetic approach to obtain meso-Uracil-BODIPY

An effective and convenient protocol for the synthesis of 1-Substituted-6-formyl-uracil derivatives has been developed. A three-step sequence has allowed obtaining new 6-Formyl uracil with various substituents at N-1, in large quantity using low-cost precursors. Uracil molecules containing an aldehyde group have been used as useful precursors for the preparation of meso-(1’-Substituted-6’-uracil)-BODIPY derivatives. In this way, regioselectively functionalized BODIPYs directly connected to a nucleobase were prepared in yields from 30 to 45%. MALDI-TOF mass spectrometry, NMR, UV-vis absorption, steady-state and time-resolved fluorescence spectroscopies have been used to characterize the structures and the spectroscopic/photophysical properties of the obtained dyes.

Effect of N'-Benzyl Substituted Uracil and the Analogues on HIV-1 Inhibition

The aim of the research is to study the effect of the synthesis of uracil derivatives on the HIV-1 activity. To achieve the goal, the following tasks were determined: to study the specificity of possible compounds for HIV-1 treatment; to synthesize uracil derivatives; to study the effect of the compounds on HIV-1 replication in vitro and select the most optimal concentrations, considering the cytotoxic effect; to determine the most effective anti-HIV-1 compounds for further research. Thus, nine new uracil analogues have been synthesized and proved to be inhibitors of HIV-1. Key structural modifications included replacement of the 6-chloro group of 1-benzyl-6-chloro-3-(3,5-dimethylbenzyl) uracil by other functional groups or N (1)-alkylation of 3-(3,5-dimethylbenzyl)-5-fluorouracil. These compounds showed only micromolar potency against HIV-1 in MT-4, though two of them; 6-azido-1-benzyl-3-(3,5-dimethylbenzyl) uracil and 6-amino-1-benzyl-3-(3,5-dimethylbenzyl) uracil were highly potent (half maximal effective concentration =0.081 and 0.069μM) and selective (selectivity index =679 and 658), respectively. Structure-activity relationships among the newly synthesized uracil analogues suggest the importance of the H-bond formed between 6-amino group of 6-amino-1-benzyl-3-(3,5-dimethylbenzyl) uracil and amide group of HIV-1 reverse transcriptase. Two 6-substituted 1-benzyl-3-(3,5-dimethylbenzyl) uracils, (6-azido-1-benzyl-3-(3,5-dimethylbenzyl) uracil and 6-amino-1-benzyl-3-(3,5-dimethylbenzyl) uracil) were discovered as novel anti-HIV agents. Compound’s activity against HIV-1 was determined based on inhibition of virus-induced cytopathogenicity in MT-4 cells. The compounds were tested for efficacy in infected cells and cytotoxicity. These compounds should be further pursued for their toxicity and pharmacokinetics in vivo as well as antiviral activity against non-nucleoside reverse transcriptase inhibitor-resistant strains. Thus, it will contribute to the development of a new generation of compounds effective against different viruses, considering their quickly mutation and increased resistance.