RESUMO
The antiretroviral and anti-oxidant profile of a series of new C-2 and C-7 substituted benzo[b]furans was explored by employing well established antiviral and antioxidant protocols. The most potent antioxidant compound tested was analog 7, which bears an OH at C-7 and a benzoyl group at C-2. In the influenza A type H3N2 virus screens analog 8a was almost five-fold more active than its counterparts and equipotent to rimantadine and amantadine. In the influenza B screening all of the new compounds tested were at least ten-fold more active than the control drug amantadine. The anti-HIV screening, using acutely infected MT-4 cells, showed that compound 8f (n = 4), was fifteen-fold more active than its monomer congeners, 8a and 8c, d and almost five-fold more potent than monomer 8b and dimer 8f (n = 3).
Assuntos
Antioxidantes/síntese química , Antioxidantes/farmacologia , Antivirais/síntese química , Antivirais/farmacologia , Benzofuranos/síntese química , Benzofuranos/farmacologia , Retroviridae/efeitos dos fármacos , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Efeito Citopatogênico Viral/efeitos dos fármacos , Feminino , HIV-1/efeitos dos fármacos , HIV-2/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/química , Peroxidação de Lipídeos/efeitos dos fármacos , Orthomyxoviridae/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344 , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Células Tumorais CultivadasRESUMO
A series of new ether lipid-3'-azido-3'-deoxythymidine (AZT) conjugates (11a-g) were synthesized and evaluated for anti-HIV activity. The effect of chirality on the antiviral activity was examined through the synthesis of AZT conjugates bearing alkoxypropanols in the lipid portion of the molecule (11a-d). In addition, the long alkyl chain of alkoxyethyl ether lipid-AZT analogs was replaced with aromatic groups (11e-g), and the effect of this structural modification on activity is reported. The results of the biological tests indicate that analogs with a methyl group alpha to the phosphate moiety (11c,d) exhibit a marked degree of stereoselectivity with regard to their anti-HIV activity. Also, replacement of the long alkyl chain with aromatic groups in the oxyalkyl ether phospholipid-AZT conjugates leads to substantially more potent compounds (11e-g) with an anti-HIV activity comparable to that of AZT.