RESUMO
Oxime derivatives of dehydrocholic acid and its esters were designed for anti-hepatitis B virus (HBV) drugs according to principles of assembling active chemical fragments. Twelve compounds were synthesized from dehydrocholic acid by esterification and oxime formation, and their anti-hepatitis B virus (HBV) activities were evaluated with HepG 2.2.15 cells. Results showed that 5 compounds exhibited more effective inhibition of HBeAg than positive control, among them 2b-3 and 2b-1 showed significant anti-HBV activities on inhibiting secretion of HBeAg (IC50 (2b-3) = 49.39 ± 12.78 µM, SI (2b-3) = 11.03; IC50 (2b-1) = 96.64 ± 28.99 µM, SI (2b-1) = 10.35) compared to the Entecavir (IC50 = 161.24 µM, SI = 3.72). Molecular docking studies showed that most of these compounds interacted with protein residues of heparan sulfate proteoglycan (HSPG) in host hepatocyte and bile acid receptor.
Assuntos
Antivirais/síntese química , Ácido Desidrocólico/análogos & derivados , Antígenos E da Hepatite B/metabolismo , Oximas/síntese química , Antivirais/química , Antivirais/farmacologia , Esterificação , Guanina/análogos & derivados , Guanina/farmacologia , Células Hep G2 , Proteoglicanas de Heparan Sulfato/química , Proteoglicanas de Heparan Sulfato/metabolismo , Antígenos E da Hepatite B/química , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/metabolismo , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Oximas/química , Oximas/farmacologia , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismoRESUMO
A series of condensation products of cholic and dehydrocholic acids with (L)-aminoacids was prepared and tested in vitro for antimicrobial activity. The derivatives of cholic acid with basic aminoacids showed significant activity, especially marked when (L)-arginine was the condensed aminoacid.
Assuntos
Antibacterianos/síntese química , Ácidos Cólicos/síntese química , Ácido Desidrocólico/análogos & derivados , Aminoácidos/síntese química , Bactérias/efeitos dos fármacos , Fenômenos Químicos , Química , Ácidos Cólicos/farmacologia , Ácido Desidrocólico/síntese química , Ácido Desidrocólico/farmacologiaRESUMO
The synthesis of derivatives of dehydro-and deoxy-colic acids with L-lysine and Lysil-lysine with antibacterial activity, is here described. Results show no antibacterial activity of dehydrocolic acid derivatives, while deoxycol-lys-OH-HCl, and particularly deoxycol-lys-NH2-2HCl, seem to be very effective on Gram-positive bacteria at 5 mug/ml, and on Gram-negatives at 25 mug/ml.