RESUMO
Natural product analogs are significant sources for therapeutic agents. To capitalize efficiently on the effective features of naturally occurring substances, a natural product-based library production platform has been devised at Aurigene for drug lead discovery. This approach combines the attractive biological and physicochemical properties of natural product scaffolds, provided by eons of natural selection, with the chemical diversity available from parallel synthetic methods. Virtual property analysis, using computational methods described here, guides the selection of a set of natural product scaffolds that are both structurally diverse and likely to have favorable pharmacokinetic properties. The experimental characterization of several in vitro ADME properties of twenty of these scaffolds, and of a small set of designed congeners based upon one scaffold, is also described. These data confirm that most of the scaffolds and the designed library members have properties favorable to their utilization for creating libraries of lead-like molecules.
Assuntos
Alcaloides/química , Fatores Biológicos/química , Desenho de Fármacos , Preparações Farmacêuticas/síntese química , Extratos Vegetais/química , Inibidores das Enzimas do Citocromo P-450 , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Indicadores e Reagentes , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Modelos Moleculares , SolubilidadeRESUMO
Bacoside A, the putative bioactive component of the Indian medicinal plant Bacopa monnieri, was found to be a mixture of saponins with bacoside A3 (1), bacopaside II (2), jujubogenin isomer of bacopasaponin C (3) and bacopasaponin C (4) as major constituents. An HPLC method together with an optimised extraction procedure was developed for the estimation of 1-4 in B. monnieri to enable standardisation of the latter. Concentration ranges of the analytes in samples of B. monnieri collected from different regions of India were 0.14-0.85% (w/w) (1), 0.12-0.69% (2), 0.05-0.72% (3) and 0.05-0.44% (4). The importance of using bacoside A, with known concentrations of 1-4, as a reference standard for the routine analysis of B. monnieri is highlighted. Two common flavonoids, luteolin and apigenin, were present in all samples of B. monnieri.
Assuntos
Bacopa/química , Saponinas/química , Triterpenos/química , Cromatografia Líquida de Alta Pressão , Estrutura Molecular , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificaçãoRESUMO
Ethanolic extracts of six Indian medicinal plants, piperine, guggulsterone E and guggulsterone Z were tested for cytotoxicity using brine shrimp lethality test. Piper longum showed most potent cytotoxic activity. Piperine, guggulsterone E and guggulsterone Z showed potent activity with LC(50) 2.4, 8.9 and 4.9, respectively.