ABSTRACT
A new brominated pyrrolactam stylissaol A (1) together with four known analogues, 2-bromoaldisine, aldisine, spongiacidin D, and Z-hymenialdisine, were isolated from the EtOAc extract of marine sponge Stylissa massa collected in Myanmar. The absolute configuration at C-10 of 1 was determined as R by the electronic circular dichroism (ECD) data. Among the isolated compounds, 2-bromoaldisine showed anti-Viral Protein R (Vpr) activity against TREx-HeLa-Vpr cells with an effective dose of 10 µM and its potency was comparable to that of positive control damnacanthal.
Subject(s)
Alkaloids/chemistry , Antiviral Agents/chemistry , Porifera/chemistry , Alkaloids/isolation & purification , Alkaloids/metabolism , Animals , Antiviral Agents/isolation & purification , Antiviral Agents/metabolism , Circular Dichroism , HeLa Cells , Humans , Molecular Conformation , Myanmar , Porifera/metabolism , vpr Gene Products, Human Immunodeficiency Virus/antagonists & inhibitors , vpr Gene Products, Human Immunodeficiency Virus/genetics , vpr Gene Products, Human Immunodeficiency Virus/metabolismABSTRACT
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
Jatropha multifida is a medicinal plant that belongs to the Euphorbiaceae family. Our investigation revealed that the chloroform extract of J. multifida stems showed anti-melanin deposition activity against α-melanocyte stimulating hormone (α-MSH)- and 3-isobutyl-1-methylxanthine (IBMX)-induced melanogenesis in the mouse melanoma cell line (B16-F10). Further fractionation and purification of the major constituents led to the isolation of two coumarins (1 and 2) and seven known lignoids (3-9). All isolated compounds exhibited anti-melanin deposition activities against the mouse melanoma cell line (B16-F10) with IC50 values ranging from 37.5 to 560.1 µM, without any cytotoxicity even at high concentrations, except for 8. Further mechanistic studies suggested that 9 downregulated tyrosinase mRNA expression, while the anti-melanin deposition activities of 4 and 8 appeared to be unrelated to tyrosinase inhibition and the downregulated expression of the key melanogenesis-associated mRNAs. These results suggested that J. multifida could possess potent skin whitening ingredients.
Subject(s)
Jatropha/chemistry , Melanins/metabolism , Melanoma, Experimental/drug therapy , Plant Extracts/pharmacology , alpha-MSH/pharmacology , Animals , Cell Line, Tumor , Down-Regulation/drug effects , Mice , Monophenol Monooxygenase/metabolismABSTRACT
Four new bis-iridoid glycosides, saungmaygaosides A-D (1-4), and six known iridoid glycosides (5-10) were isolated from the n-butanol extract of the stems of Picrorhiza kurroa collected in Myanmar. Their structures were elucidated by extensive spectroscopic techniques. All of the isolates were assayed for anti-Vpr activity, using TREx-HeLa-Vpr cells. Among the isolates, saungmaygaoside D (4), sylvestroside IV dimethyl acetal (7), and sweroside (8) were the most potent inhibitors with effective doses of 5 and 10⯵M, respectively, without showing any notable cytotoxicities.