ABSTRACT
Three neo-clerodane diterpenoids, including two new tinocordifoliols A (1) and B (2) and one known tinopanoid R (3), were isolated from the ethyl acetate-soluble fraction of the 70% ethanol extract of Tinospora cordifolia stems. The structures were elucidated by various spectroscopic methods, including one dimensional (1D) and 2D-NMR, high resolution-electrospray ionization (HR-ESI)-MS, and electronic circular dichroism (ECD) data. The T. cordifolia extract and all isolated compounds 1-3 possessed arginase I inhibitory activities. Among them, 3 exhibited moderate competitive inhibition of human arginase I (IC50 = 61.9 µM). Furthermore, docking studies revealed that the presence of a ß-substituted furan in 3 may play a key role in the arginase I inhibitory activities.
Subject(s)
Arginase , Diterpenes, Clerodane , Enzyme Inhibitors , Molecular Docking Simulation , Plant Stems , Tinospora , Tinospora/chemistry , Arginase/antagonists & inhibitors , Arginase/metabolism , Diterpenes, Clerodane/pharmacology , Diterpenes, Clerodane/chemistry , Diterpenes, Clerodane/isolation & purification , Humans , Plant Stems/chemistry , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/isolation & purification , Structure-Activity Relationship , Molecular Structure , Molecular Conformation , Dose-Response Relationship, DrugABSTRACT
Arginases are bimanganese enzymes involved in many human illnesses, and thus are targets for disease treatments. The screening of traditional medicinal plants demonstrated that an ethanol extract of Curcuma comosa rhizomes showed significant human arginase I and II inhibitory activity, and further fractionation led to the isolation of three known guaiane sesquiterpenoids, alismoxide (1), 7α,10α-epoxyguaiane-4α,11-diol (2) and guaidiol (3). Tests of their inhibitory activities on human arginases I and II revealed that 1 exhibited selective and potent competitive inhibition for human arginase I (IC50 = 30.2 µM), whereas the other compounds lacked inhibitory activities against human arginases. To the best of our knowledge, this is the first demonstration of human arginase I inhibitory activity by a sesquiterpenoid. Thus, 1 is a primary and specific inhibitory molecule against human arginase I.
Subject(s)
Curcuma , Sesquiterpenes , Humans , Rhizome , Arginase , Sesquiterpenes/pharmacology , Molecular StructureABSTRACT
In the search of cytotoxic dihydrochalcones, this investigation led to the isolation of seven compounds (1-7) from Eriosema glomeratum and the preparation of eight derivatives (8-15). The cytotoxicity of samples was evaluated against lung (A549), breast (MCF-7), and cervical (HeLa) human cancer cells. The CH2Cl2/MeOH extract of the aerial part had strong cytotoxicity against all cells [IC50 11.2 (MCF-7), 8.4 (HeLa) and 13.1 (A549) µg/mL]. A strong activity was also displayed by the n-hexane fraction on MCF-7 (IC50 11.2 µg/mL). The precursor 3 and the derivative 8 were specifically found as strong cytotoxic agents toward MCF-7 (7.6 µM) and HeLa (3.1 µM), respectively and were more effective than the positive control. Derivatives 8 (3.1 µM) and 9 (21.3 µM) against HeLa were most potent than their precursor 3 (23.7 µM). This is the first preparation of 8-14 as well as the cytotoxicity of 3, 4, 8-15, fractions, and extract.
ABSTRACT
SmltD is an ATP-dependent ligase that catalyzes the condensation of UDP-MurNAc-l-Ala and l-Glu to form UDP-MurNAc-l-Ala-l-Glu, in the newly discovered peptidoglycan biosynthesis pathway of a Gram-negative multiple-drug-resistant pathogen, Stenotrophomonas maltophilia. Phytochemical investigation of the 70% ethanol extract from Woodfordia fruticosa flowers collected in Myanmar led to the identification of anti-SmltD active flavonoids, kaempferol 3-O-(6''-galloyl)-ß-d-glucopyranoside (1), astragalin (2), and juglalin (3). Among them, 1 showed the most potent SmltD inhibitory activity. An enzyme steady-state kinetic study revealed that 1 exerted competitive inhibition with respect to ATP. The results of this study provided an attractive foundation for the further development of novel inhibitors of SmltD.
Subject(s)
DNA Ligase ATP/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Flavonoids/pharmacology , Peptidoglycan/biosynthesis , Woodfordia/chemistry , DNA Ligase ATP/metabolism , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Flavonoids/chemistry , Flavonoids/isolation & purification , Molecular Structure , Peptidoglycan/chemistry , Stenotrophomonas maltophilia/enzymology , Structure-Activity RelationshipABSTRACT
The ocotillol (OCT)-type saponins have been known as a tetracyclic triterpenoid, possessing five- or six-membered epoxy ring in the side chain. Interestingly, this type saponin was mostly found in Panax vietnamensis Ha et Grushv., Araliaceae (VG), hence making VG unique from the other Panax spp. Five OCT-type saponins, majonoside R2, vina-ginsenoside R2, majonoside R1, pseudoginsenoside RT4, vina-ginsenoside R11, together with three protopanaxadiol (PPD)-type saponins and four protopanaxatriol (PPT)-type saponins from VG were evaluated for their antimelanogenic activity. All of isolates were found to be active. More importantly, the five OCT-type saponins inhibited melanin production in B16-F10 mouse melanoma cells, without showing any cytotoxicity. Besides ginsenoside Rd and ginsenoside Rg3 in PPD and notoginsenoside R1 in PPT-type saponins, majonoside R2 was the most potent melanogenesis inhibitory activity in OCT-type saponins. In this article, we highlighted antimelanogenic activity of OCT-type saponins and potential structure-activity relationship (SAR) of ginsenosides. Our results suggested that OCT-type saponins could be used as a depigmentation agent.