ABSTRACT
In this study, we synthesized a series of amide and mitochondria-targeted derivatives with 3-O-acetyl-11-keto-ß-boswellic acid (AKBA) as the parent structure and an ethylenediamine moiety as the link chain. Compound 5e, a mitochondrial-targeting potential derivative, showed significantly stronger antitumor activity than that of AKBA, and it could induce vacuolization of A549 cells and stimulate the production of reactive oxygen species (ROS) in a time- and concentration-dependent manner. The antioxidant N-acetylcysteine (NAC) could inhibit the ROS level but could not suppress vacuolization and cell death induced by 5e. Further studies demonstrated that 5e caused abnormal opening of mitochondrial permeability transition pore (MPTP) and a decrease of mitochondrial membrane potential; additionally, it caused cell cycle arrest in G0/G1 but did not induce apoptosis. 5e represented a compound with improved antiproliferative effects for cancer therapy working through new mechanisms.
ABSTRACT
Two pairs of diastereoisomeric isoindoline alkaloids, xylarins A-D (1-4), were isolated from the endolichenic fungus Xylaria sp. Xylarins A and B (1 and 2) possess a previously undescribed 5/6/5-5/6 polycyclic scaffold, featuring a combination of a novel dihydrobenzofurone unit and an isoindoline unit, while xylarins C and D (3 and 4) contain an additional N,N-dimethylaniline at the C-3' position. Their structures were elucidated by comprehensive spectroscopic analyses combined with single-crystal X-ray diffraction and electronic circular dichroism calculations. The plausible biosynthetic pathways and gene clusters for 1-4 were proposed. Compound 1 exhibited significant antithrombotic activity.
Subject(s)
Alkaloids/chemistry , Isoindoles/chemistry , Xylariales/chemistry , Alkaloids/isolation & purification , Biosynthetic Pathways , Circular Dichroism , Crystallography, X-Ray , Isoindoles/isolation & purification , Molecular StructureABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Genus Sapium, belonging to Euphorbiaceae family, has a wide distribution in Asia and in temperate and tropical regions of Africa and America. The various parts of Sapium species have been used in traditional Chinese herbal medicine for the treatment of edema, skin-related diseases, bacterial infections, cancers, diabetes, and other ailments. AIM OF THE STUDY: A comprehensive and updated review on the phytochemistry, pharmacology, and traditional medicinal uses of Sapium has been summarized and discussed to facilitate further exploitation of the therapeutic values of Sapium species. MATERIALS AND METHODS: The relevant information of Sapium species was collected by scientific search engines including Elsevier, Google Scholar, Scifinder, and CNKI (China national knowledge infrastructure), and Master's dissertations and Summon from Shandong University Library. RESULTS: Phytochemical studies revealed that approximately 259 compounds including terpenoids, phenylpropanoids, flavonoids, tannins, steroids, alkaloids, etc. have been isolated and identified from Sapium species, among which terpenoids, phenylpropanoids and tannins are the main constituents. Pharmacological in vitro and in vivo studies revealed that the extracts and pure compounds possessed significant antibacterial, antiinflammatory, antioxidant, antihypertensive effects, cytotoxicity, antidiabetic, molluscicidal effects. Terpenoids, phenylpropanoids, tannins, flavonoids, and alkaloids may be responsible for these activities. CONCLUSIONS: The traditional uses, phytochemistry, and pharmacology described in this article demonstrated that the plants of Sapium genus possess many different types of compounds exhibiting wide range of biological activities, and they have high medicinal value and potential in the treatment of a variety of diseases. Detailed phytochemical studies have been conducted on only twelve species in the literature. More wide-ranging studies are still needed to explore this genus. Most of the existing bioactivity-related studies were implemented on crude extracts. More in-depth studies are necessary to reveal the links between the traditional uses and bioactivity in the future.