Avaliação in silico de inserções com boro em moléculas com atividade farmacológica

AUTOR(ES)

Adão Lincon Bezerra Montel

DATA DE PUBLICAÇÃO

2006

RESUMO

The growth of leukemia incidence, cardiac problems and global AIDS epidemic, with appearing of resistant forms of HIV, stimulated the search of new medications. In this work, we investigated new active pharmacologic compounds based on boron including the anti-HIV drugs. The interest in boron compounds with pharmacologic activity has increased in recent years with the first drug approved by FDA. This drug is based on boron and used in neoplasm treatment. In fact, the strong inhibitory activity on enzymes of this compounds makes them promising in pharmacological research. In our project we investigated two analogues of an antiretroviral named nevirapine that inhibits an essential enzyme in HIV replication. The new analogues are boron compounds based on DNA, RNA, valproic acid and salicylic acid. In our calculations we used quantum mechanical approach to evaluate interactions of these molecules with the conserved amino acids of replications enzyme of HIV as well as some electronic molecular properties. The results show an increased interaction between nevirapine modified molecule and amino acid one. The results suggest also that one of the compounds can form an irreversible complex with HIVs enzyme. In the studies with DNA and RNA molecules, we observed a covalent complex formation between the Watson-Crick pairs accompanied by changes in LUMO orbital distribution. In the Valproic and salicylic acid molecules we observed changes in the molecular orbital distribution as well as in the potential map (especially in valproic acid). The substitution of carboxylic acid by boronic acid indicates an increasing pharmacological activity. In all analyzed cases, we have seen important modifications induced by boron introduction that evince a pharmacological potential for these molecules.

ASSUNTO(S)

quimica ácido bórico boro aids (doença) farmacologia nevirapina

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