RESUMEN
A series of omega-undecanoic amides of lup-20(29)-en-28-oic acid derivatives were synthesized and evaluated for activity in CEM 4 and MT-4 cell cultures against human immunodeficiency virus type 1 (HIV-1) strain IIIB/LAI. The potent HIV inhibitors which emerged, compounds 5a, 16a, and 17b, were all derivatives of betulinic acid (3beta-hydroxylup-20(29)-en-28-oic acid). No activity was found against HIV-2 strain ROD. Compound 5a showed no inhibition of HIV-1 reverse transcriptase activity with poly(C).oligo(dG) as template/primer, nor did it inhibit HIV-1 protease. Additional mechanistic studies revealed that this class of compounds interfere with HIV-1 entry in the cells at a postbinding step.
Asunto(s)
Antivirales/síntesis química , VIH-1/efectos de los fármacos , Triterpenos/síntesis química , Triterpenos/farmacología , Antivirales/farmacología , Inhibidores Enzimáticos/farmacología , VIH-2/efectos de los fármacos , Humanos , Modelos Moleculares , Estructura Molecular , Triterpenos Pentacíclicos , Inhibidores de la Transcriptasa Inversa/farmacología , Relación Estructura-Actividad , Triterpenos/química , Células Tumorales Cultivadas , Ácido BetulínicoRESUMEN
14-diethoxyacetoxy daunorubicin (R.P. 33 921) was chosen among a series of new daunorubicin analogues. Its preparation from daunorubicin and its biological activities are described. It displays an antitumoral activity in mice with a better chemotherapeutic index than daunorubicin and doxorubicin.