Dimeric pyrrole-imidazole alkaloids: sources, structures, bioactivities and biosynthesis.

Pyrrole-imidazole alkaloids (PIAs) constitute a highly diverse and densely functionalized subclass of marine natural products. Among them, the uncommon dimeric PIAs with ornate molecular architectures, attractive biological properties and interesting biosynthetic origin have spurred a considerable interest of chemists and biologists. The present review comprehensively summarized 84 dimeric PIAs discovered during the period from 1981 to September 2022, covering their source organisms, chemical structures, biological activities as well as biosynthesis. For a better understanding, these structurally intricate PIA dimers are firstly classified and presented according to their carbon skeleton features as well as biosynthesis pathways. Furthermore, relevant summaries focusing on the source organisms and the associated bioactivities of these compounds belonging to different chemical classes are also provided, which will help elucidate the fascinating chemistry and biology of these unusual PIA dimers.

Secondary metabolites from marine sponges of the genus Agelas: a comprehensive update insight on structural diversity and bioactivity.

As one of the most common marine sponges in tropical and subtropical oceans, the sponges of the genus Agelas, have emerged as unique and yet under-investigated pools for discovery of natural products with fabulous molecular diversity and myriad interesting biological activities. The present review highlights the chemical structure and biological activity of 355 compounds that have been isolated and characterized from the members of Agelas sponges, over the period of about five decades (from 1971 to November 2021). For a better understanding, these numerous compounds are firstly classified and presented according to their carbon skeleton as well as their biosynthetic origins. Relevant summaries focusing on the source organism and the associated bioactivity of these compounds belonging to different chemical classes are also provided. This review highlights sponges of the genus Agelas as exciting source for discovery of intriguing natural compounds.

Extraction of Proanthocyanidins from Chinese Wild Rice (Zizania latifolia) and Analyses of Structural Composition and Potential Bioactivities of Different Fractions.

Due to the importance of proanthocyanidin bioactivity and its relationship with chemical structure, ultrasound-assisted extraction and purification schemes were proposed to evaluate the proanthocyanidin content and analyze the structural composition and potential bioactivities of different proanthocyanidin fractions from Chinese wild rice (Zizania latifolia). Following an optimized extraction procedure, the crude wild rice proanthocyanidins (WRPs) were purified using n-butanol extraction, chromatography on macroporous resins, and further fractionation on Sephadex LH-20 to yield six specific fractions (WRPs-1-WRPs-6) containing proanthocyanidin levels exceeding 524.19 ± 3.56 mg/g extract. Structurally, (+)-catechin, (-)-epicatechin, and (-)-epigallocatechin were present as both terminal and extension units, and (-)-epicatechin was the major extension unit, in each fraction. This is the first preparation of WRP fractions with a different mean degree of polymerization (mDP), ranging from 2.66 ± 0.04 to 10.30 ± 0.46. A comparison of the bioactivities of these fractions revealed that fractions WRPs-1-WRPs-5 had significant DPPH radical scavenging activities, whereas fraction WRPs-6 with a high mDP showed better α-glucosidase and pancreatic lipase inhibitory effects. These findings should help define possible applications of WRPs to functional foods or nutraceuticals.

Metabolites from the Paracel Islands Soft Coral Sinularia cf. molesta.

Five new oxygenated sesquiterpenes, molestins A⁻D (1, 3⁻5) and epi-gibberodione (2), three new cyclopentenone derivatives, ent-sinulolides C, D, and F ((+)-9⁻(+)-11), one new butenolide derivative, ent-sinulolide H ((+)-13), and one new cembranolide, molestin E (14), together with 14 known related metabolites (6⁻8, (⁻)-9⁻(⁻)-11, (±)-12, (⁻)-13, 15⁻19) were isolated from the Paracel Islands soft coral Sinularia cf. molesta. The structures and absolute configurations were elucidated based on comprehensive spectroscopic analyses, quantum chemical calculations, and comparison with the literature data. Compound 5 is the first example of a norsesquiterpene with a de-isopropyl guaiane skeleton isolated from the genus Sinularia. Molestin E (14) exhibited cytotoxicities against HeLa and HCT-116 cell lines with IC50 values of 5.26 and 8.37 µM, respectively. Compounds 4, 5, and 8 showed significant inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 218, 344, and 1.24 µM, respectively.

Partial Purification, Identification, and Quantitation of Antioxidants from Wild Rice (Zizania latifolia).

To provide further insights into the potential health-promoting antioxidants from wild rice (Zizania latifolia), which is an abundant but underutilized whole grain resource in East Asia, a partial purification based on D101 macroporous resin was carried out for the purification and enrichment of the antioxidants from the bioactive ethanol extracts of wild rice. On that basis, 34 phenolic compounds in the antioxidant fractions were identified by a high-performance liquid chromatography-linear ion trap quadrupole-Orbitrap-mass spectrometry (HPLC-LTQ-Orbitrap-MSn). The results suggested that phenolic acids could be enriched in the 10% ethanol-eluted fraction whereas flavonoids (including procyanidins and flavonoid glycosides) could be enriched in 20⁻30% ethanol-eluted fractions. A quantitative analysis determined by the multiple reaction monitoring mode of the ultra-performance liquid chromatography-triple quadrupole-tandem mass spectrometry (UPLC-QqQ-MS/MS) revealed a high content of procyanidins in wild rice. Compared with phenolic acids, flavonoids may contribute more to the potent antioxidant activity of wild rice. This is the first study on the antioxidants from wild rice Z. latifolia. These findings provide novel information on the functional components of wild rice, and will be of value to further research and development on Z. latifolia.

Cytotoxic and Antiviral Triterpenoids from the Mangrove Plant Sonneratia paracaseolaris.

A chemical investigation was conducted on the aerial parts of the mangrove plant Sonneratia paracaseolaris, yielding five new triterpenoid paracaseolins A-E (1-4, and 11) together with twelve known analogues (5-10, 12-17). Their structures were established by extensive spectroscopic methods and comparisons their spectroscopic data with those of the known related compounds. The cytotoxicities against P388, HeLa, A549, and K562 tumor cell lines and anti-H1N1 (Influenza A virus) activities for the isolates were evaluated. Compound 4 showed potent cytotoxicity against the A549 cell line with an IC50 value of 1.89 µM, and compound 1 exhibited significant anti-H1N1 virus activity with an IC50 value of 28.4 µg/mL. A preliminary structure activity relationship was discussed.

Pyrrole Derivatives and Diterpene Alkaloids from the South China Sea Sponge Agelas nakamurai.

Two pairs of new non-brominated racematic pyrrole derivatives, (±)-nakamurine D (1) and (±)-nakamurine E (2), two new diterpene alkaloids, isoagelasine C (16) and isoagelasidine B (21), together with 13 known pyrrole derivatives ((±)-3 - 15), five known diterpene alkaloids (17 - 20, 22) were isolated from the South China Sea sponge Agelas nakamurai. The racemic mixtures, compounds 1 - 4, were resolved into four pairs of enantiomers, (+)-1 and (-)-1, (+)-2 and (-)-2, (+)-3 and (-)-3, and (+)-4 and (-)-4, by chiral HPLC. The structures and absolute configurations were elucidated on the basis of comprehensive spectroscopic analyses, quantum chemical calculations, quantitative measurements of molar rotations, application of van't Hoff's principle of optical superposition, and comparison with the literature data. The NMR and MS data of compound 3 are reported for the first time, as the structure was listed in SciFinder Scholar with no associated reference. These non-brominated pyrrole derivatives were found in this species for the first time. Compound 18 showed valuable cytotoxicities against HL-60, K562, and HCT-116 cell lines with IC50 values of 12.4, 16.0, and 19.8 µm, respectively. Compounds 16 - 19, 21, and 22 showed potent antifungal activities against Candida albicans with MIC values ranging from 0.59 to 4.69 µg/ml. Compounds 16 - 19 exhibited moderate antibacterial activities against Proteusbacillus vulgaris (MIC values ranging from 9.38 to 18.75 µg/ml).