RESUMO
Investigations on the twigs and leaves of Antirhea chinensis have led to the discovery of two undescribed pentacyclic triterpenoids (1 and 2) and nine known analogs. Compounds 1 and 2, each assigned as the ursane and 24-noroleanane-type triterpenoids, featuring similar oxidation pattern of 3ß,6ß,19α-trihydroxy-28-carboxyl. Their structures were elucidated via comprehensive analyses of spectroscopic data. Compound 1 displayed potent anti-HIV activity (EC50 =1.24â µM) and high selectivity index (SI >32.3).
Assuntos
Rubiaceae , Triterpenos , Triterpenos/química , Folhas de Planta/química , Extratos Vegetais/química , Estrutura MolecularRESUMO
Dengue virus (DENV) causes a variety of difficult-to-treat diseases that threaten almost half of the world's population. Currently, no effective vaccine or antiviral therapy is available. We have examined a series of synthetic resveratrol analogs to identify potential anti-DENV agents. Here, we demonstrate that two resveratrol analogs, PNR-4-44 and PNR-5-02, possess potent anti-DENV activity with EC50 values in the low nanomolar range. These two resveratrol analogs were shown to mainly target viral RNA translation and viral replication, but PNR-5-02 is also likely to target cellular factors inside host cells. Although the precise molecular mechanism(s) mediating anti-DENV activities have not been elucidated, further structure-guided design might lead to the development of newer improved resveratrol derivatives that might have therapeutic value. J. Med. Virol. 89:397-407, 2017. © 2016 Wiley Periodicals, Inc.
Assuntos
Antivirais/farmacologia , Vírus da Dengue/efeitos dos fármacos , Estilbenos/farmacologia , Vírus da Dengue/fisiologia , Avaliação Pré-Clínica de Medicamentos , Reposicionamento de Medicamentos , Humanos , Testes de Sensibilidade Microbiana , Biossíntese de Proteínas/efeitos dos fármacos , Resveratrol , Replicação Viral/efeitos dos fármacosRESUMO
Two new alkaloids, flueggether A (1) and virosinine A (2), were isolated from a Chinese medicinal plant, Flueggea virosa. Their structures were assigned via spectroscopic methods with the absolute configurations of 1 and 2 being established by X-ray diffraction analysis and calculated electronic circular dichroism data, respectively. Compound 1 represents the first example with an ether bridge of Securinega alkaloid oligomers, and 2 bears a new heterocyclic backbone. Both alkaloids showed mild in vitro anti-HIV activity.
Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Euphorbiaceae/química , Alcaloides/química , Fármacos Anti-HIV/química , Cristalografia por Raios X , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Plantas Medicinais/químicaRESUMO
BACKGROUND: Due to resistance to all classes of anti-HIV drugs and drug toxicity, there is a need for the discovery and development of new anti-HIV drugs. METHODS: HIV-1 inhibitors were identified and biologically characterized for mechanism of action. RESULTS: We identified a dibenzocyclooctadiene lignan, termed HDS2 that possessed anti-HIV activity against a wide variety of viral strains with EC50 values in the 1-3 µM range. HDS2 was shown to act as an NNRTI by qPCR and in vitro enzyme assays. CONCLUSIONS: This compound provides a new scaffold for further optimization of activity through structure-guided design.
Assuntos
Ciclo-Octanos/farmacologia , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/efeitos dos fármacos , HIV-1/enzimologia , Lignanas/farmacologia , Inibidores da Transcriptase Reversa/farmacologia , Linhagem Celular , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , HIV-2/efeitos dos fármacos , HIV-2/enzimologia , Humanos , Especificidade da Espécie , Relação Estrutura-AtividadeRESUMO
Eighteen new diterpenoids, named eurifoloids A-R (1-18), including ingenane (1 and 2), abietane (3-7), isopimarane (8-12), and ent-atisane (13-18) types, along with four known analogues were isolated from Euphorbia neriifolia. Eurifoloid M (13) represents a rare class of ent-atisane-type norditerpenoid. Eurifoloids E (5) and F (6) exhibited significant anti-HIV activities, with EC50 values of 3.58 ± 0.31 (SI = 8.6) and 7.40 ± 0.94 µM (SI = 10.3), respectively.