10.1080/15257770903169999
The study investigates the synthesis and antiviral properties of a new family of nucleoside analogues derived from pyrazinone, aiming to explore their potential as anti-HIV agents. The researchers synthesized compounds 5a, 5b, and 5c, which are analogues of the nucleoside 2′,3′-didehydro-2′,3′-dideoxythymidine (d4T). The synthesis process involved several steps, including selective deprotection of hydroxyl groups, formation of bisxanthate intermediates, and radical reactions to introduce double bonds. The compounds were characterized using techniques like 1H NMR and infrared spectroscopy. The study found that these compounds did not exhibit antiviral activity against HIV-1 or cytotoxic effects in tested cell lines. The chemicals involved include pyrazinone nucleosides, methanolic ammonia for deprotection, carbon disulfide, sodium hydride, and methyl iodide for bisxanthate formation, and tributylphosphine-borane for the radical reaction. The roles of these chemicals are crucial in the structural modification of the nucleoside analogues to enhance their lipophilicity and potential membrane permeability, although the final compounds did not show the desired antiviral activity.
10.1016/j.bmc.2009.11.013
The research describes the development of a novel anti-HIV polymeric prodrug: chitosan-O-isopropyl-50-O-d4T monophosphate conjugate. The study aims to improve the antiviral efficacy of nucleoside reverse transcriptase inhibitors (NRTIs) and reduce their side effects by constructing a nanosized NRTI monophosphate-polymer conjugate using d4T as a model NRTI. Key chemicals involved in the research include chitosan, a biodegradable and biocompatible polysaccharide used as the polymeric vehicle, and d4T (stavudine), an NRTI used in the treatment of HIV infection. The synthesis of the chitosan-d4T conjugate was achieved through the Atherton–Todd reaction under mild conditions, resulting in a water-soluble prodrug with a degree of substitution (DS) of 17.0%. Other chemicals used in the synthesis process include O-isopropyl-5-H-phosphonate of d4T, synthesized using phosphorus trichloride as a phosphorylation reagent, and various reagents such as triethylamine, tetrachloromethane, and sodium tripolyphosphate (TPP) for the preparation of nanoparticles. The study evaluated the anti-HIV activity and cytotoxicity of the conjugate in MT4 cells, prepared nanoparticles for enhanced delivery to viral reservoirs, and conducted in vitro drug release studies to assess the controlled release of d4T monophosphate derivatives.
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