RESUMEN
To design and synthesis a series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates with more potent anti-HBV activity, adefovir dipivoxil was used as lead compound, according to the results of enhanced oral bioavailability and antiviral activities of nucleoside L-amino acid ester prodrugs. Eleven novel L-amino acid ester prodrugs of acyclic nucleoside phosphonates were designed and synthesized, their anti-HBV activities were evaluated in HepG2 2.2.15 cells. Eight compounds exhibited antiviral activity, and compound 11 showed the most potent anti-HBV activity and highest selective index in vitro (EC50 0.0952 micromol x L(-1), SI 69523). Moreover, by analyzing the primary structure and activity relationship of these compounds, it could be suggested that L-amino acid ester strategy has significant potential in the acyclic nucleoside phosphonates prodrug design.
Asunto(s)
Humanos , Aminoácidos , Química , Antivirales , Farmacología , Línea Celular Tumoral , Virus de la Hepatitis B , Neoplasias Hepáticas , Patología , Virología , Nucleósidos , Farmacología , Organofosfonatos , Farmacología , Profármacos , FarmacologíaRESUMEN
Ten novel compounds were designed and synthesized on the basis of compound 1, their insulin-sensitizing activities were evaluated in 3T3-L1 cells. Results showed that compound 10 exhibited strong differentiation-stimulating activity on 3T3-L1 cells model, which indicated that compound 10 may possess well insulin-sensitizing activity.
Asunto(s)
Animales , Ratones , Células 3T3-L1 , Benzopiranos , Farmacología , Diseño de Fármacos , Hipoglucemiantes , Farmacología , Insulina , FarmacologíaRESUMEN
Thirteen benzopyran derivatives were synthesized and their activity stimulating the differentiation of preadipocytes into adipocytes were evaluated with 3T3-L1 cells. Compound 8 was also tested for its hypoglycemic activity on db diabetes mice model. Results indicated that compounds 3, 8 and 11 exhibited strong differentiation-stimulating activity on 3T3-L1 cells model, and compound 8 can reduce the blood-sugar level of db diabetes mice dramatically.
Asunto(s)
Animales , Ratones , Células 3T3-L1 , Adipocitos , Benzopiranos , Química , Farmacología , Glucemia , Metabolismo , Diferenciación Celular , Diabetes Mellitus Experimental , Sangre , Hipoglucemiantes , Química , FarmacologíaRESUMEN
<p><b>AIM</b>To design and synthesize compounds with insulin-sensitizing activity.</p><p><b>METHODS</b>Using association principle of drug design, ten title compounds were designed and synthesized on the basis of known compounds with insulin-sensitizing activity, and their insulin-sensitizing activity were evaluated on 3T3-L1 pre-adipocyte cells.</p><p><b>RESULTS</b>One of the synthesized compounds showed strong insulin-sensitizing activity in vitro.</p><p><b>CONCLUSION</b>This compound may possess good sugar-lowering activity, and will be chosen for further hypoglycemic evaluation in vivo.</p>