Therapeutic potential of boswellic acids: an update patent review (2016-2023).

INTRODUCTION: Boswellic acids (BAs) are a group of pentacyclic triterpenoids of the ursane and oleanane type. They have shown very interesting biological properties that have led to the development of a number of synthesis protocols. Both natural BAs and their synthetic derivatives may be useful in the treatment of a variety of cancers, viral infections and inflammatory diseases. AREAS COVERED: This review covers patents relating to the therapeutic activities of natural BAs and their synthetic derivatives. The latest patented studies of boswellic acids (are summarized by using the keywords 'boswellic acid,' in SciFinder, PubMed, and Google Patents and databases in the year from 2016 to 2023. EXPERT OPINION: Boswellic acids have shown potent antiviral, anticancer and anti-inflammatory potential. Few BAs analogues have been prepared by modification at the C24-CO2H functional groups. In particular, the C-24 amide and amino analogues have shown enhanced anticancer effects compared to the parent AKBA. In addition, BAs have the ability to form conjugates with other antiviral, anti-inflammatory and anticancer drugs that synergistically enhance their biological efficacy. In addition, this conjugation strategy will increase the solubility and bioavailability of BAs, which is one of the most important issues in the development of BAs.

Access to New Cytotoxic Triterpene and Steroidal Acid-TEMPO Conjugates by Ugi Multicomponent-Reactions.

Multicomponent reactions, especially the Ugi-four component reaction (U-4CR), provide powerful protocols to efficiently access compounds having potent biological and pharmacological effects. Thus, a diverse library of betulinic acid (BA), fusidic acid (FA), cholic acid (CA) conjugates with TEMPO (nitroxide) have been prepared using this approach, which also makes them applicable in electron paramagnetic resonance (EPR) spectroscopy. Moreover, convertible amide modified spin-labelled fusidic acid derivatives were selected for post-Ugi modification utilizing a wide range of reaction conditions which kept the paramagnetic center intact. The nitroxide labelled betulinic acid analogue 6 possesses cytotoxic effects towards two investigated cell lines: prostate cancer PC3 (IC50 7.4 ± 0.7 µM) and colon cancer HT29 (IC50 9.0 ± 0.4 µM). Notably, spin-labelled fusidic acid derivative 8 acts strongly against these two cancer cell lines (PC3: IC50 6.0 ± 1.1 µM; HT29: IC50 7.4 ± 0.6 µM). Additionally, another fusidic acid analogue 9 was also found to be active towards HT29 with IC50 7.0 ± 0.3 µM (CV). Studies on the mode of action revealed that compound 8 increased the level of caspase-3 significantly which clearly indicates induction of apoptosis by activation of the caspase pathway. Furthermore, the exclusive mitochondria targeting of compound 18 was successfully achieved, since mitochondria are the major source of ROS generation.

Rewarding compounds identified from the medicinal plant Rhodiola rosea.

Preparations of Rhodiola rosea root are widely used in traditional medicine. They can increase life span in worms and flies, and have various effects related to nervous system function in different animal species and humans. However, which of the compounds in R. rosea is mediating any one of these effects has remained unknown in most cases. Here, an analysis of the volatile and non-volatile low-molecular-weight constituents of R. rosea root samples was accompanied by an investigation of their behavioral impact on Drosophila melanogaster larvae. Rhodiola rosea root samples have an attractive smell and taste to the larvae, and exert a rewarding effect. This rewarding effect was also observed for R. rosea root extracts, and did not require activity of dopamine neurons that mediate known rewards such as sugar. Based on the chemical profiles of R. rosea root extracts and resultant fractions, a bioactivity-correlation analysis (AcorA) was performed to identify candidate rewarding compounds. This suggested positive correlations for - among related compounds - ferulic acid eicosyl ester (FAE-20) and ß-sitosterol glucoside. A validation using these as pure compounds confirmed that the correlations were causal. Their rewarding effects can be observed even at low micromolar concentrations and thus at remarkably lower doses than for any known taste reward in the larva. We discuss whether similar rewarding effects, should they be observed in humans, would indicate a habit-forming or addictive potential.

Metabolites profiling of Ziziphus leaf taxa via UHPLC/PDA/ESI-MS in relation to their biological activities.

Ziziphus plants are well recognized for their nutritive and medicinal value worldwide, albeit their chemical profile has yet to be fully reported. The secondary metabolites profile of three traditionally used Ziziphus leaf accessions was investigated via ultra-high performance liquid chromatography coupled to photodiode array and electrospray ionization mass detectors (UHPLC/PDA/ESI-MS). A total of 102 metabolites were characterized revealing the first holistic approach onto Ziziphus leaf metabolome and to include the first report of several novel flavonoids and cyclopeptide alkaloids. Fragmentation pattern for cyclopeptide alkaloids was proposed via ESI-MS. Principal component analysis (PCA) revealed close metabolite resemblance among Z. spina-christi and Z. mauritiana leaf specimens found enriched in saponins and distinct from that of Z. jujuba in which quercetin-3-O-(2-pentosyl)-rhamnoside was most abundant. Further, in-vitro antioxidant, anti-inflammatory and antidiabetic assays revealed for Z. spina-christi and Z. mauritiana strong effects compared to Z. jujuba and in correlation with their metabolites repertoire.

Nor-guanacastepene pigments from the Chilean mushroom Cortinarius pyromyxa.

For the first time, the pigment composition of basidiocarps from the Chilean mushroom Cortinarius pyromyxa was studied under various aspects like phylogeny, chemistry and antibiotic activity. A molecular biological study supports the monotypic position of C. pyromyxa in subgenus Myxacium, genus Cortinarius. Four undescribed diterpenoids, named pyromyxones A-D, were isolated from fruiting bodies of C. pyromyxa. Their chemical structures were elucidated based on comprehensive one- and two-dimensional NMR spectroscopic analysis, ESI-HRMS measurements, as well as X-ray crystallography. In addition, the absolute configurations of pyromyxones A-D were established with the aid of JH,H, NOESY spectra and quantum chemical CD calculation. The pyromyxones A-D possess the undescribed nor-guanacastane skeleton. Tested pyromyxones A, B, and D exhibit only weak activity against gram-positive Bacillus subtilis and gram-negative Aliivibrio fischeri as well as the phytopathogenic fungi Botrytis cinerea, Septoria tritici and Phytophthora infestans.

The unusual fragmentation of long-chain feruloyl esters under negative ion electrospray conditions.

Long-chain ferulic acid esters, such as eicosyl ferulate (1), show a complex and analytically valuable fragmentation behavior under negative ion electrospay collision-induced dissociation ((-)-ESI-CID) mass spectrometry, as studied by use of a high-resolution (Orbitrap) mass spectrometer. In a strong contrast to the very simple fragmentation of the [M + H]+ ion, which is discussed briefly, the deprotonated molecule, [M - H]- , exhibits a rich secondary fragmentation chemistry. It first loses a methyl radical (MS2 ) and the ortho-quinoid [M - H - Me]-• radical anion thus formed then dissociates by loss of an extended series of neutral radicals, Cn H2n + 1 • (n = 0-16) from the long alkyl chain, in competition with the expulsion of CO and CO2 (MS3 ). The further fragmentation (MS4 ) of the [M - H - Me - C3 H7 ]- ion, discussed as an example, and the highly specific losses of alkyl radicals from the [M - H - Me - CO]-• and [M - H - Me - CO2 ]-• ions provide some mechanistic and structural insights.

Phytochemical Profiles and Antimicrobial Activities of Allium cepa Red cv. and A. sativum Subjected to Different Drying Methods: A Comparative MS-Based Metabolomics.

Plants of the Allium genus produce sulphur compounds that give them a characteristic (alliaceous) flavour and mediate for their medicinal use. In this study, the chemical composition and antimicrobial properties of Allium cepa red cv. and A. sativum in the context of three different drying processes were assessed using metabolomics. Bulbs were dried using either microwave, air drying, or freeze drying and further subjected to chemical analysis of their composition of volatile and non-volatile metabolites. Volatiles were collected using solid phase micro-extraction (SPME) coupled to gas chromatography-mass spectrometry (GC/MS) with 42 identified volatiles including 30 sulphur compounds, four nitriles, three aromatics, and three esters. Profiling of the polar non-volatile metabolites via ultra-performance liquid chromatography coupled to high resolution MS (UPLC/MS) annotated 51 metabolites including dipeptides, flavonoids, phenolic acids, and fatty acids. Major peaks in GC/MS or UPLC/MS contributing to the discrimination between A. sativum and A. cepa red cv. were assigned to sulphur compounds and flavonoids. Whereas sulphur conjugates amounted to the major forms in A. sativum, flavonoids predominated in the chemical composition of A. cepa red cv. With regard to drying impact on Allium metabolites, notable and clear separations among specimens were revealed using principal component analysis (PCA). The PCA scores plot of the UPLC/MS dataset showed closer metabolite composition of microwave dried specimens to freeze dried ones, and distant from air dried bulbs, observed in both A. cepa and A. sativum. Compared to GC/MS, the UPLC/MS derived PCA model was more consistent and better in assessing the impact of drying on Allium metabolism. A phthalate derivative was found exclusively in a commercial garlic preparation via GC/MS, of yet unknown origin. The freeze dried samples of both Allium species exhibited stronger antimicrobial activities compared to dried specimens with A. sativum being in general more active than A. cepa red cv.

Spin-labelled diketopiperazines and peptide-peptoid chimera by Ugi-multi-component-reactions.

For the first time, spin-labelled coumpounds have been obtained by isonitrile-based multi component reactions (IMCRs). The typical IMCR Ugi-protocols offer a simple experimental setup allowing structural variety by which labelled diketopiperazines (DKPs) and peptide-peptoid chimera have been synthesized. The reaction keeps the paramagnetic spin label intact and offers a simple and versatile route to a large variety of new and chemically diverse spin labels.