RESUMO
Irlbacholine and a series of related analogues were synthesized and their antifungal activities against Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus were assessed. The natural bisphosphocholine, irlbacholine, was the most potent compound, its 22-carbon chain length appearing to be optimal.
Assuntos
Antifúngicos/isolamento & purificação , Fosforilcolina/análogos & derivados , Plantas Medicinais/química , Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , América Central , Cryptococcus neoformans/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Fosforilcolina/isolamento & purificação , Fosforilcolina/farmacologia , América do SulRESUMO
Cryptolepine (1) is a rare example of a natural product whose synthesis was reported prior to its isolation from nature. In the previous paper we reported the discovery of cryptolepine's antihyperglycemic properties. As part of a medicinal chemistry program designed to optimize natural product lead structures originating from our ethnobotanical and ethnomedical field research, a series of substituted and heterosubstituted cryptolepine analogues was synthesized. Antihyperglycemic activity was measured in vitro and in an NIDDM mouse model to generate the first structure-bioactivity study about the cryptolepine nucleus.
Assuntos
Alcaloides/farmacologia , Hipoglicemiantes/farmacologia , Indóis , Plantas Medicinais/química , Quinolinas , Células 3T3 , Tecido Adiposo/citologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Alcaloides/síntese química , Alcaloides/química , Animais , Transporte Biológico/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Glucose/metabolismo , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Alcaloides Indólicos , Camundongos , Camundongos Obesos , Relação Estrutura-AtividadeRESUMO
Using an ethnobotanical approach in combination with in vivo-guided fractionation as a means for lead discovery, cryptolepine was isolated as an antihyperglycemic component of Cryptolepis sanguinolenta. Two syntheses of cryptolepine, including an unambiguous synthesis, are reported. The hydroiodide, hydrochloride, and hydrotrifluoromethanesulfonate (hydrotriflate) salts of cryptolepine were synthesized, and a comparison of their spectral properties and their in vitro activities in a 3T3-L1 glucose transport assay is made. Cryptolepine and its salt forms lower blood glucose in rodent models of type II diabetes. While a number of bioactivities have been reported for cryptolepine, this is the first report that cryptolepine possesses antihyperglycemic properties.