The isolation and structure elucidation of six new bacterial metabolites [spoxazomicin D (2), oxachelins B and C (4, 5), and carboxamides 6–8] and 11 previously reported bacterial metabolites (1, 3, 9–12a, and 14–18) from Streptomyces sp. RM-14-6 is reported. Structures were elucidated on the basis of comprehensive 1D and 2D NMR and mass spectrometry data analysis, along with direct comparison to synthetic standards for 2, 11, and 12a,b. Complete 2D NMR assignments for the known metabolites lenoremycin (9) and lenoremycin sodium salt (10) were also provided for the first time. Comparative analysis also provided the basis for structural revision of several previously reported putative aziridine-containing compounds [exemplified by madurastatins A1, B1, C1 (also known as MBJ-0034), and MBJ-0035] as phenol-dihydrooxazoles. Bioactivity analysis [including antibacterial, antifungal, cancer cell line cytotoxicity, unfolded protein response (UPR) modulation, and EtOH damage neuroprotection] revealed 2 and 5 as potent neuroprotectives and lenoremycin (9) and its sodium salt (10) as potent UPR modulators, highlighting new functions for phenol-oxazolines/salicylates and polyether pharmacophores.

The assessment of glycosyl-scanning to expand the molecular and functional diversity of metabolites from the underground coal mine fire-associated Streptomyces sp. RM-14-6 is reported. Using the engineered glycosyltransferase OleD Loki and a 2-chloro-4-nitrophenylglycoside-based screen, six metabolites were identified as substrates of OleD Loki, from which 12 corresponding metabolite glycosides were produced and characterized. This study highlights the first application of the 2-chloro-4-nitrophenylglycoside-based screen toward an unbiased set of unique microbial natural products and the first reported application of the 2-chloro-4-nitrophenylglycoside-based transglycosylation reaction for the corresponding preparative synthesis of target glycosides. Bioactivity analysis (including antibacterial, antifungal, anticancer, and EtOH damage neuroprotection assays) revealed glycosylation to attenuate the neuroprotective potency of 4, while glycosylation of the structurally related inactive spoxazomicin C (3) remarkably invoked neuroprotective activity.

Two strobane diterpenoids, strobols A (1) and B (2), 15 new pimarane diterpenoids (3–6 and 8–18), and the known compounds kirenol (19), darutigenol (20), and ent-2β,15,16,19-tetrahydroxypimar-8(14)-ene (7) were isolated from the aerial parts of Siegesbeckia pubescens Makino. The structures of the new compounds were established based on the interpretation of HRESIMS and NMR analysis. The configurations of 1, 6, and 17 were confirmed by X-ray crystallographic data. Compounds 3, 5, and 11 inhibited the migration of MB-MDA-231 breast cancer cells induced by the chemokine epithelial growth factor, with IC₅₀ values of 4.26, 3.45, and 9.70 μM, respectively.

The genus Rhodocodon (Hyacinthaceae sensu APG II) is endemic to Madagascar, and its phytochemistry has not been described previously. The phytochemistry of three species in this genus has been investigated, and eight compounds, including three bufadienolides (compounds 1, 4, and 5), a norlignan (2), and four homoisoflavonoids (compounds 3 and 6–8), have been isolated and identified. Compounds 1–3 and 6–8 have not been described previously. The COX-2 inhibitory activity of compound 6 and compound 7 acetate (compound 7A) was investigated on isolated colorectal cancer cells. Compounds 6 and 7A inhibited COX-2 by 10% and 8%, respectively, at a concentration of 12.5 μM compared to 12% for 1 mM aspirin (the positive control).

Six new eremophilane-type sesquiterpenes, namely, nigriterpenes A–F (1–6), and one new phenolic compound, named 2-hydroxymethyl-3-pentylphenol (7), along with fomannoxin alcohol, 3-butyl-7-hydroxyphthalide, scytalone, and fomannoxin were isolated from the ethyl acetate extracts of the fermented broths of termite nest-derived Xylaria nigripes, which has long been used as a traditional Chinese medicine for treating insomnia and depression. Their structures were elucidated on the basis of spectroscopic data analysis and compared with the literature. All the pure isolates were evaluated against lipopolysaccharide-induced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) expression, and NO production in murine brain microglial BV-2 cells. Of the compounds tested, nigriterpene C (3) and fomannoxin alcohol exerted significant inhibitory effects on two induced enzymes and NO production without any significant cellular toxicity. The most potent compound, 3, exhibited concentration-dependent inhibition on NO production and iNOS and COX-2 expression with IC₅₀ values of 21.7 ± 4.9, 8.1 ± 2.3, and 16.6 ± 5.5 μM, respectively. These results indicated that the potential anti-inflammatory effects of nigriterpene C (3) and fomannoxin alcohol on murine brain microglial BV-2 cells may provide a rationale for the traditional medical uses of X. nigripes for treating insomnia and depression.

Eupatorium tremulum is a South American shrub reported to cause cattle digestive intoxication, of which the volatile oil, mainly composed by bisabolane- and amorphane-type sesquiterpenoids, exhibits high quantitative variability. This report describes the application of chemometric tools for the identification of volatile compounds that characterize phenophasical changes in the plant. Preblooming, blooming, and postblooming specimens were paired-sampled and submitted to hydrodistillation and GC-MS analysis. Differential results were analyzed by orthogonal projection to latent structures-discriminant analysis (OPLS-DA), and the substances with different distribution in each phase were highlighted. Mean results between phases were submitted to factor analysis (FA), and correlations between the variables were demonstrated. Preblooming to blooming phase change was characterized by decreased levels of amorpha-4-en-7-ol (13) and epi-α-bisabolol (19) and increased amounts of amorpha-4,7(11)-diene (1). Blooming to postblooming change was characterized by decreases in 1, germacrene D (2), and β-bisabolene (4) and increases in 13 and 19. Finally, enhanced levels of 1, 4, and 2 reflected the change from the postblooming to the preblooming phase. FA revealed a strong correlation in the variability between the bisabolane hydrocarbons, possibly related to its common enzymatic origin. Another strong source of negative correlation showed bisabolane- and amorphane-type alcohols, on one side, and amorphane-type furans, on the other side, to occur in two alternative oxidation routes. Finally, 1 was strongly negatively correlated to its oxidized furan and ketofuran derivatives [verboccidentafuran (16) and 3-oxo-verboccidentafuran (23)] and additionally to a third compound, putatively identified as a biosynthetic intermediate between this hydrocarbon and the furans, amorpha-4,7(11)-dien-8-one (20).

(+)-Rutamarin inhibits EBV lytic DNA replication with an IC₅₀ of 7.0 μM. (−)-Chalepin, a (−)-rutamarin derivative, was isolated from the whole plant of Ruta graveolens and used as a precursor of (−)-rutamarin. Altogether, 28 (−)-rutamarin derivatives were synthesized starting from (−)-chalepin. Of these, 16 compounds (2a–e, 3b–e, 3g, 4f, 4k, 4m–p) were found to be more potent against EBV lytic DNA replication than (−)-chalepin. Compounds 4m, 4n, and 4p exhibited IC₅₀ values of 1.5, 0.32, and 0.83 μM and showed selectivity index values (SI) of 801, 211, and >120, respectively. Thus, compounds 4m, 4n, and 4p are considered promising leads for further laboratory investigation.

Spiroapplanatumines A–Q (1–12, 14–16, 18, and 20), new spiro meroterpenoids respectively bearing a 6/5/7 or 6/5/5 ring system, along with three known compounds, spirolingzhines A, B, and D, were isolated from the fruiting bodies of the fungus Ganoderma applanatum. Their structures including absolute configurations were assigned by using spectroscopic methods, ECD and ¹³C NMR calculations, and single-crystal X-ray diffraction analysis. Biological evaluation of all the compounds disclosed that compounds 7 and 8 inhibited JAK3 kinase with IC₅₀ values of 7.0 ± 3.2 and 34.8 ± 21.1 μM, respectively.

Six new epipolythiodioxopiperazine (ETP) alkaloids, penicisulfuranols A–F (1–6), were isolated from the mangrove endophytic fungus Penicillium janthinellum HDN13-309. All structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data and ECD calculations. They belong to the unusual family of ETPs containing sulfur atoms on both α- and β-positions of amino acid residues and a rare 1,2-oxazadecaline core moiety. In addition, compounds 1–6 also possess a rare spiro-furan ring and 1–3 showed cytotoxicity with IC₅₀ values ranging from 0.1 to 3.9 μM.

Seven azaphilones, montagnuphilones A–G (1–7), together with previously known azaphilones 8–11, were encountered in Montagnulaceae sp. DM0194, an endophytic fungus isolated from submerged roots of Persicaria amphibia. The structures of 1–7 were elucidated on the basis of their MS and NMR spectroscopic analysis. Compounds 1–8 were evaluated for their cytotoxicity and ability to inhibit nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 macrophage cells. Among these, none were found to be cytotoxic to RAW264.7 cells up to 100.0 μM, but 8, 5, and 2 showed NO inhibitory activity with IC₅₀ values of 9.2 ± 0.9, 25.5 ± 1.1, and 39.6 ± 1.8 μM, respectively.

Chemical analysis of the chloroform extract of the aerial parts of the Algerian plant Pulicaria undulata exhibiting anti-inflammatory activity resulted in the isolation of 10 new humulene sesquiterpenoids, 1–10, belonging to the asteriscunolide family of compounds. The structure and relative configuration have been defined by NMR data, whereas the absolute configuration has been established by ECD analysis. Compounds 1–10 include enantiomers of the known asteriscunolides A–D and tetrahydroasteriscunolide previously reported from the genera Asteriscus and Nauplius. Compounds 1 and 10 showed in vitro anti-inflammatory activity by inhibiting heat-induced albumin denaturation with IC₅₀ values of 23.76 and 220.42 μM.

Six new spongian diterpene derivatives, ceylonins A–F (1–6), were isolated from the Indonesian marine sponge Spongia ceylonensis along with spongia-13(16),14-dien-19-oic acid (7). They contained three additional carbons in ring D to supply an ether-bridged bicyclic ring system. Their structures were elucidated by analyzing NMR spectroscopic data and calculated ECD spectra in comparison to experimental ECD spectra. The bicyclic ring system may be derived from the major metabolite 7 and a C₃ unit (an acrylic acid equivalent) through an intermolecular Diels–Alder reaction, which was experimentally supported by the formation of 1–6 from 7 and acrylic acid. The inhibitory effects of the isolated compounds on the RANKL-induced formation of multinuclear osteoclasts in RAW264 macrophages were examined.

Inspired by the discovery of the antimalarial drug artemisinin from a traditional Chinese medicine (TCM), a natural product library of 44 lindenane-type sesquiterpenoids was assessed for activities against the Dd2 chloroquine-resistant strain of the malaria parasite Plasmodium falciparum. These compounds were mainly isolated from plants of the Chloranthus genus, many species of which are named “Sikuaiwa” in TCM and have long been used to treat malaria. The compounds consisted of 41 sesquiterpenoid dimers and three monomers, including the 12 new dimers 1–12 isolated from Chloranthus fortunei. The results showed that 16 dimers exhibited potent antiplasmodial activities (<100 nM); in particular, compounds 1, 14, and 19 exhibited low nanomolar activities with IC₅₀ values ranging from 1 to 7 nM, which is comparable to the potency of artemisinin, and selectivity index values toward mammalian cells greater than 500. A comprehensive structure–activity relationship study indicated that three functional groups are essential and two motifs can be modified.

The previous assignment of the type C skeleton of polycyclic polyprenylated acylphloroglucinols (PPAPs) was controversial and proved to be incorrect in this study. The structures of the type C PPAPs (3–6) were revised to corresponding type A structures (3a–6a) via ¹³C NMR spectroscopic analysis and a quantum computational chemistry method. Therefore, only types A and B PPAPs are likely present in plants of the family Clusiaceae.

Thirteen new metabolites, including the polyoxygenated cyclohexene derivatives cleistodiendiol (1), cleistodienol B (3), cleistenechlorohydrins A (4) and B (5), cleistenediols A–F (6–11), cleistenonal (12), and the butenolide cleistanolate (13), 2,5-dihydroxybenzyl benzoate (cleistophenolide, 14), and eight known compounds (2, 15–21) were isolated from a MeOH extract of the leaves of Cleistochlamys kirkii. The purified metabolites were identified by NMR spectroscopic and mass spectrometric analyses, whereas the absolute configurations of compounds 1, 17, and 19 were established by single-crystal X-ray diffraction. The configuration of the exocyclic double bond of compound 2 was revised based on comparison of its NMR spectroscopic features and optical rotation to those of 1, for which the configuration was determined by X-ray diffraction. Observation of the co-occurrence of cyclohexenoids and heptenolides in C. kirkii is of biogenetic and chemotaxonomic significance. Some of the isolated compounds showed activity against Plasmodium falciparum (3D7, Dd2), with IC₅₀ values of 0.2–40 μM, and against HEK293 mammalian cells (IC₅₀ 2.7–3.6 μM). While the crude extract was inactive at 100 μg/mL against the MDA-MB-231 triple-negative breast cancer cell line, some of its isolated constituents demonstrated cytotoxic activity with IC₅₀ values ranging from 0.03–8.2 μM. Compound 1 showed the most potent antiplasmodial (IC₅₀ 0.2 μM) and cytotoxic (IC₅₀ 0.03 μM, MDA-MB-231 cell line) activities. None of the compounds investigated exhibited translational inhibitory activity in vitro at 20 μM.

To date, 16 members of the ammosamide family of natural products have been discovered, and except for ammosamide D each of these metabolites is characterized by an unusual chlorinated pyrrolo[4,3,2-de]quinoline skeleton. Several ammosamides have been shown to inhibit quinone reductase 2, a flavoenzyme responsible for quelling toxic oxidative species in cells or for killing cancer cells outright. Treatment of the extract from an ammosamide-producing culture (Streptomyces strain CNR-698) with a thiol-based reagent designed to label electrophilic natural products produced an ammosamide C-thiol adduct. This observation led us to hypothesize, and then demonstrate through experimentation, that all of the other ammosamides are derived from ammosamide C via nonenzymatic processes involving exposure to nucleophiles, air, and light. Like many established electrophilic natural products, reaction with the thiol probe suggests that ammosamide C is itself an electrophilic natural product. Although ammosamide C did not show substantial cytotoxicity against cancer cells, its activity against a marine Bacillus bacterial strain may reflect its ecological role.

Two new cyclic octadepsipeptides, octaminomycins A (1) and B (2), were isolated from a microbial metabolite fraction library of Streptomyces sp. RK85-270 based on Natural Products Plot screening. Their structures were elucidated on the basis of HRESIMS, 1D and 2D NMR spectroscopic data, and MS/MS experiments for sequence analysis. The absolute configurations of the constituent amino acid residues were determined by a combination of single-crystal X-ray diffraction and Marfey’s methodology. Notably, octaminomycins A (1) and B (2) showed good in vitro antiplasmodial activity against chloroquine-sensitive as well as chloroquine-resistant strains with no cytotoxicity up to 30 μM.

Human pancreatic cancer cell lines have a remarkable tolerance to nutrition starvation, which enables them to survive under a tumor microenvironment. The search for agents that preferentially inhibit the survival of cancer cells under low nutrient conditions represents a novel antiausterity strategy in anticancer drug discovery. In this investigation, a methanol extract of the rhizomes of Boesenbergia pandurata showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions, with a PC₅₀ value of 6.6 μg/mL. Phytochemical investigation of this extract led to the isolation of 15 compounds, including eight new cyclohexene chalcones (1–8). The structures of the new compounds were elucidated by NMR spectroscopic data analysis. Among the isolated compounds obtained, isopanduratin A1 (14) and nicolaioidesin C (15) exhibited potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrition-deprived conditions, with PC₅₀ values of 1.0 and 0.84 μM, respectively.

A new anthranilic acid derivative (1) was isolated from a Philippine sponge, Oscarella stillans (Bergquist and Kelly). The structure of compound 1, named oscarellin, was determined as 2-amino-3-(3′-aminopropoxy)benzoic acid from spectroscopic data and confirmed by synthesis. We examined the immunomodulating effect of compound 1 and its mechanism in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Our data indicated that the expression of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were significantly reduced by the pretreatment of 1 (0.1–10 μM) for 2 h. In addition, compound 1 suppressed activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH₂-termimal kinase (JNK), but not p38 mitogen-activated protein kinase (MAPK) in LPS-stimulated RAW 264.7 cells. Compound 1 abrogated LPS-induced nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) activities, whereas the induction of activating transcription factor-3 (ATF-3) was increased. Taken together, our results suggest that compound 1 attenuates pro-inflammatory cytokines via the suppression of JNK, ERK, AP-1, and NF-κB and the activation of the ATF-3 signaling pathway.

Six new iridal-type triterpenoids containing an unprecedented cyclopentane ring, polycycloiridals E–J (1–6), were isolated from a large-scale re-extraction of Iris tectorum. A possible biosynthesis pathway is postulated. The known spirioiridotectal D (7) was also obtained in the current investigation, and its structure was unequivocally defined using X-ray diffraction data. Compound 7 suppressed LPS-activated NO production in the BV2 cell line with an IC₅₀ value of 0.54 μM.

Five new polyhydroxylated hydroanthraquinone derivatives, namely, 8-hydroxyconiothyrinone B (1), 8,11-dihydroxyconiothyrinone B (2), 4R,8-dihydroxyconiothyrinone B (3), 4S,8-dihydroxyconiothyrinone B (4), and 4S,8-dihydroxy-10-O-methyldendryol E (5), were isolated and identified from the culture extract of Talaromyces islandicus EN-501, an endophytic fungus obtained from the inner tissue of the marine red alga Laurencia okamurai. The structures of these compounds were established on the basis of detailed interpretation of their NMR and mass spectroscopic data, and the structures and absolute configurations of compounds 1 and 2 were confirmed by X-ray crystallographic analysis, while the absolute configurations of compounds 3–5 were determined by TDDFT calculations of the ECD spectra. The antimicrobial, antioxidant, and cytotoxic activities of compounds 1–5 were evaluated.

Fourteen new natural products, namely, 2-[(Z)-styryl]-5-geranylresorcin-1-carboxylic acid (1), amorfrutin D (2), 4-O-demethylamorfrutin D (3), 8-geranyl-3,5,7-trihydroxyflavanone (4), 8-geranyl-5,7,3′-trihydroxy-4′-methoxyisoflavone (5), 6-geranyl-5,7,3′-trihydroxy-4′-methoxyisoflavone (6), 8-geranyl-7,3′-dihydroxy-4′-methoxyisoflavone (7), 3-O-demethyldalbinol (8), 6a,12a-dehydro-3-O-demethylamorphigenin (9), (6aR,12aR,5′R)-amorphigenin (10), amorphispironones B and C (11 and 12), resokaempferol 3-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside-7-O-α-l-rhamnopyranoside (13), and daidzein 7-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside (14), together with 40 known compounds, were isolated from the fruits of Amorpha fruticosa. The structures of the new compounds were elucidated by 1D and 2D NMR spectroscopic analysis as well as from the mass spectrometry data. ECD calculations were performed to determine the absolute configurations of 11 and 15. Compounds 1, 4–6, and 16–23 showed potent to moderate antibacterial activities against several Gram-positive bacteria with MIC values ranging from 3.1 to 100 μM. In addition, compounds 11 and 24–33 were significantly cytotoxic against the L5178Y mouse lymphoma cell line and exhibited IC₅₀ values from 0.2 to 10.2 μM.

Brevipolides K–O (1–5), five new cytotoxic 6-(6′-cinnamoyloxy-2′,5′-epoxy-1′-hydroxyheptyl)-5,6-dihydro-2H-pyran-2-ones (IC₅₀ values against six cancer cell lines, 1.7–10 μM), were purified by recycling HPLC from Hyptis brevipes. The structures, containing a distinctive tetrahydrofuran ring, were established by comprehensive quantum mechanical calculations and experimental spectroscopic analysis of their NMR and ECD data. Detailed analysis of the experimental NMR ¹H–¹H vicinal coupling constants in comparison with the corresponding DFT-calculated values at the B3LYP/DGDZVP level confirmed the absolute configuration of 3 and revealed its conformational preferences, which were further strengthened by NOESY correlations. NMR anisotropy experiments by the application of Mosher’s ester methodology and chemical correlations were also used to conclude that this novel brevipolide series (1–5) share the same absolute configuration corresponding to C-6(R), C-1′(S), C-2′(R), C-5′(S), and C-6′(S).

From an extract prepared from the grain-based culture of Malbranchea flavorosea two new polyketides, namely, 8-chloroxylarinol A (1) and flavoroseoside (2), along with the known compounds xylarinol A (3), xylarinol B (4), massarigenins B and C (5 and 6), and clavatol (7), were isolated. The structures of 1 and 2 were elucidated using spectroscopic methods and corroborated by single-crystal X-ray diffraction analysis. In the case of compound 2 the absolute configuration at the stereogenic centers was established according to the method of Flack. In addition, the X-ray structure of compound 6 is reported for the first time. Compounds 3, 4, and 6 significantly inhibited yeast α-glucosidase. Compound 6 also inhibited the postprandial peak during an oral sucrose tolerance assay when tested in vivo, using normal and NA/STZ-induced hyperglycemic mice.

Despite the increasing attention on the therapeutic potential of Curcuma longa (turmeric), the biological activities of curcuminoids other than curcumin are not well understood. Here, we investigated antivasoconstrictive activities of C. longa extract and its ingredients using freshly isolated rat aortic rings. C. longa extract significantly suppressed agonist-stimulated vasoconstriction, and cyclocurcumin was found to be the most potent (IC₅₀ against phenylephrine-induced vasoconstriction: 14.9 ± 1.0 μM) among the 10 tested ingredients including four curcuminoids. Cyclocurcumin significantly inhibited contraction of vascular smooth muscle, which was mediated by the suppression of myosin-light-chain phosphorylation and calcium influx via the L-type calcium channel. The inhibitory effect of cyclocurcumin was observed to be reversible and without cytotoxicity. Taken together, we demonstrated that cyclocurcumin, a bioactive ingredient in C. longa, may have a therapeutic potential as a novel antivasoconstrictive natural product.

Monascustin (1), an unusual γ-lactam, was isolated from an ethanol extract of the Monascus purpureus fermented rice. Its structure including the absolute configuration was determined by spectroscopic data analysis and confirmed by X-ray crystallography. A plausible biosynthetic pathway is discussed on the basis of amino acid derivatization. Compound 1 showed inhibitory activity against histone deacetylase 1.

Six new isochroman derivatives (annulohypoxylomans A–C, 1–3; annulohypoxylomanols A and B, 6 and 7; and annulohypoxyloside, 8), an isocoumarin (annulohypoxylomarin A, 4), and an azaphilone derivative (xylariphilone, 5) were isolated from an ethyl acetate extract derived from cultures of the endophytic fungus JS540 found in the leaves of Zizania caduciflora. The JS540 strain was identified as Annulohypoxylon truncatum. The structures of the isolated compounds were elucidated by one- and two-dimensional nuclear magnetic resonance and mass spectrometry and by comparison with related compounds from the literature. The anti-inflammatory activities of the isolated compounds were evaluated in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells. Xylariphilone (5) exhibited significant inhibitory effects on LPS-induced interleukin (IL)-6, IL-12 p40, and tumor necrosis factor (TNF)-α production with IC₅₀ values of 5.3, 19.4, and 37.6 μM, respectively.

Chemical investigation of the methanol extract of the lichen Stereocaulon paschale collected in Nunavik, Canada, led to the isolation and identification of two new dibenzofurans (1 and 3) and 11 known lichen metabolites. The structures of the new compounds were established by analysis of 1D and 2D NMR spectroscopic and high-resolution mass spectrometric data. Herein, the first isolation of ascomatic acid dibenzofuran derivatives (1–3) from a whole lichen organism is reported. In addition, some of the isolated metabolites showed antibacterial activity against the oral pathogens Porphyromonas gingivalis and Streptococcus mutans.

The isolation of bromotyrosine alkaloids, some of which are enantiomers of previously isolated compounds, has highlighted a possible enantiodivergence in their biosynthesis. Two new (1, 2) and six known bromotyrosine alkaloids (4–9), and the enantiomer (10) of a known compound, have been isolated from a Western Australian marine sponge, Pseudoceratina cf. verrucosa. The compounds inhibited the growth of multidrug-resistant and methicillin-resistant Staphylococcus aureus with comparable activity to vancomycin. In addition, one possible artifact of extraction (3) containing an ethoxy group was isolated. From analysis of the known bromotyrosine alkaloids, a biogenesis is proposed that explains the formation of antipodal natural products within this family of sponges.

Twelve benzylisoquinoline alkaloids, including pavine and phenanthroindolizidine types, were isolated from a MeOH/CH₂Cl₂ extract of Cryptocarya laevigata (stem bark) through bioactivity-guided fractionation for antitumor effects. Selected compounds were evaluated for antiproliferative activity against five human tumor cell lines, including a multidrug-resistant subline. Since more common 2,3,8,9-tetrasubstituted pavine alkaloids, such as crychine (3), exhibit very mild or no cytotoxicity, this compound type has not been well investigated for antitumor activity. Thus, this report is the first discovery of a 7-hydroxylated pavine alkaloid, (−)-neocaryachine (1), to demonstrate strong antiproliferative activity, with IC₅₀ values of 0.06 to 0.41 μM against five tested tumor cell lines, including an MDR subline. Further mechanism of action studies revealed that 1 impacts the cellular S-phase by inducing DNA double-strand breaks.

The pharmacokinetics of polymyxin B₁, polymyxin B₂, colistin A, and colistin B were investigated in a rat model following intravenous administration (0.8 mg/kg) of each individual component. Plasma and urine concentrations were determined by LC-MS/MS, and plasma protein binding was measured by ultracentrifugation. Total and unbound pharmacokinetic parameters for each component were calculated using noncompartmental analysis. All of the polymyxin components had a similar clearance, volume of distribution, elimination half-life, and urinary recovery. The area under the concentration–time curve for polymyxins B₁ and B₂ was greater than those of colistins A and B. Colistin A (56.6 ± 9.25%) and colistin B (41.7 ± 12.4%) displayed lower plasma protein binding in rat plasma compared to polymyxin B₁ (82.3 ± 4.30%) and polymyxin B₂ (68.4 ± 3.50%). These differences in plasma protein binding potentially equate to significant differences in unbound pharmacokinetics, highlighting the need for more stringent standardization of the composition of commercial products currently available for clinical use.