RESUMO
Huang-Qi (Astragali Radix) is an herbal tonic widely used in China and many other countries. It is derived from the roots of Astragalus membranaceus and A. membranaceus var. mongholicus and shows potent cardiovascular protective effects. In this article, we comprehensively reviewed 189 small molecules isolated from the two Astragalus species and discussed the interspecies chemical differences. Moreover, we summarized the pharmacological activities and mechanisms of action of Huang-Qi and its major bioactive compounds for the treatment of cardiovascular diseases. This review covers 171 references published between February 1983 and March 2020.
Assuntos
Astrágalo , Astragalus propinquus , China , Humanos , Raízes de PlantasRESUMO
Tetracyclic triterpenes and steroids are pharmacologically important molecules, and acetylation could improve their bioactivities. In this study, a highly regio- and stereo-specific acetyltransferase, AmAT19, was discovered from Astragalus membranaceus. AmAT19 could selectively catalyze the 6α-OH acetylation of four tetracyclic triterpenes and steroids. The strict selectivity is associated with different orientations of the 6α/ß-OH as indicated by molecular docking. Acetylated products 1a, 3a and 4a remarkably increased the inhibitory activity against the 3-chymotrypsin-like protease (3CLpro) of SARS-CoV-2, compared to 1, 3, and 4. AmAT19 could be a promising catalyst for specific 6α-OH acetylation to expand the molecular diversity of triterpenes and steroids.
Assuntos
Acetiltransferases/metabolismo , Astrágalo/enzimologia , Esteroides/metabolismo , Triterpenos/metabolismo , Acetilação , CatáliseRESUMO
A preliminary research on the marine fungus Fusarium sp. XBB-9 resulted in a pair of novel bisindole alkaloid enantiomers, (+)- and (-)-fusaspoid A (1a/1b) and 12 diverse compounds. One strain many compound (OSMAC) method was used to enhance as many biosynthetic pathways as possible. The structures of the compounds were elucidated by spectroscopic analysis, and the absolute configuration of 1a was determined by X-ray single-crystal diffraction analysis. Compounds 1a and 1b were tested for cytotoxic activity against HCT-15, RKO cell lines, but were inactive. Compounds 1a and 1b were the first example of bisindole alkaloids isolated from fungus Fusarium sp. XBB-9.
Assuntos
Organismos Aquáticos/química , Fusarium/química , Alcaloides Indólicos/química , Alcaloides Indólicos/isolamento & purificação , Antineoplásicos/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cristalografia por Raios X , Humanos , Alcaloides Indólicos/farmacologia , Modelos Moleculares , Espectroscopia de Prótons por Ressonância Magnética , EstereoisomerismoRESUMO
To investigate the influence of reactive oxygen species (ROS) on the secondary metabolites of the marine-derived fungus Dichotomomyces cejpii F31-1, hydrogen peroxide (H2O2) was added to the GPY culture medium. The HPLC chromatogram of the EtOAc extract of the culture broth was distinct from that of the H2O2 free GPY medium. Further study of the metabolites in the GPY medium with H2O2 resulted in the discovery of eight known compounds. Among them, (22E)-5α, 8α-epidioxyergosta-6, 22-dien-3ß-ol (2) and ergosta-4,6,8(14),22-tetraene-3-one (3) were present in the highest concentration, while ergosterol and diketopiperazines are abundant in the H2O2 free medium. Additionally, a new compound, dichocetide D (1) containing a chlorine element and a known ergosterol (10) were isolated from the H2O2 free medium. (22E)-5α, 8α-epidioxyergosta-6, 22-dien-3ß-ol (2) exhibited moderate cytotoxic activity against human prostate cancer cell line LNCaP-C4-2B.
Assuntos
Antineoplásicos/farmacologia , Aspergillus/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Aspergillus/efeitos dos fármacos , Meios de Cultura/química , Dicetopiperazinas/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Ergosterol/isolamento & purificação , Ergosterol/metabolismo , Ergosterol/farmacologia , Humanos , Peróxido de Hidrogênio/farmacologia , Indóis/química , Indóis/metabolismo , Indóis/farmacologia , Masculino , Melanoma/tratamento farmacológico , Camundongos , Estrutura Molecular , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Quinazolinas/química , Quinazolinas/metabolismo , Quinazolinas/farmacologia , Metabolismo SecundárioRESUMO
Eight previously undescribed diterpenoids, euphoroyleans A-H, including two cembranes, three ingenanes, two ent-atisanes, and one ent-kaurane, along with 22 known analogues were isolated from the whole plants of Euphorbia royleana. The structures of euphoroyleans A-H, including the absolute configurations, were elucidated by extensive spectroscopic analyses, chemical transformation, and single crystal X-ray diffractions. All the isolates were screened for their chemoreversal abilities on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) cancer cell line HepG2/DOX, and eight compounds exhibited significant activities. Among them, ingol-3,7,12-triacetate-8-benzoate, the most active MDR modulator with no obvious cytotoxicity, could enhance the efficacy of anticancer drug DOX to ca. 105 folds at 10 µM, being stronger than the positive drug verapamil. Mechanistic study revealed that ingol-3,7,12-triacetate-8-benzoate could inhibit the transport activity of P-gp rather than its expression, and the possible recognition mechanism between compounds and P-gp was predicted by molecular docking.
Assuntos
Diterpenos , Euphorbia , Subfamília B de Transportador de Cassetes de Ligação de ATP , Resistência a Múltiplos Medicamentos , Simulação de Acoplamento Molecular , Estrutura MolecularRESUMO
A germacrane sesquiterpenoid library containing 30 compounds (2-31) was constructed by structural modification of a major component aristolactone (1) from the traditional Chinese medicine Aristolochia yunnanensis. Compound 11 was identified as a promising anticardiac fibrosis agent by systematic screening of this library. 11 could inhibit the expression of fibronectin (FN), α-smooth muscle actin (α-SMA), and collagens in transforming growth factor ß 1 (TGFß1)-stimulated cardiac fibroblasts at a micromolar level and ameliorate myocardial fibrosis and heart function in abdominal aortic constriction (AAC) rats at 5 mg/kg dose. Mechanistic study revealed that 11 inhibited the TGFß/small mother against decapentaplegic (Smad) signaling pathway by targeting TGFß type I receptor (IC50 = 14.9 ± 1.6 nM). The structure-activity relationships (SARs) study indicated that the unsaturated γ-lactone ring and oxidation of C-1 were important to the activity. These findings may provide a new type of structural motif for future anticardiac fibrosis drug development.