Isolation,structure elucidation,and antibacterial evaluation of the metabolites produced by the marine-sourced Streptomyces sp. ZZ820

New indole alkaloids streptoprenylindoles A–C (1–3) and diterpenoids 18-acetyl-cyclooctatin (8), 5,18-dedihydroxy-cyclooctatin (9), and 5-dehydroxy-cyclooctatin (10) were isolated from the culture of marine-derived Streptomyces sp. ZZ820, along with known 3-cyanomethyl-6-[3-methyl-2-butenyl]indole (4), N-(2-(1H-indol-3-yl)ethylacetamide (5), 1-acetyl-β-carboline (6), indole-3-methylethanoate (7), cyclooctatin (11), and chromomycin A₃ (12). Their structures were elucidated by a combination of extensive spectroscopic analyses, ECD calculation, and the Mosher's method. Streptoprenylindoles A (1) and B (2) are enantiomers that were separated through the preparation of their Mosher esters. Three new diterpenoids (8–10) showed antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli with MIC values of 24.11–55.12?μM, while chromomycin A₃ (12) showed potent antibacterial activities against MRSA (MIC: 0.59?μM) and E. coli (MIC 0.04?μM).     

Synthesis and comparative study of cytotoxicity and anticancer activity of Chalconoid-Co(II) metal complexes with 2-hydroxychalcones analogue containing naphthalene moiety

A series of six C1–C6 chalconoid based Co(II) complexes were prepared from bi-dentate 2-hydroxychalcones ligands L1-L6 containing naphthalene moiety. All synthesized metal-complexes have been evaluated to determine their cytotoxicity and anticancer activity against liver cancer cell line (Hep G2). Compared to standard 5-fluorouracil (IC₅₀ ?= ?98.61 ?μg/mL), the metal complex C6 exhibits more potency with IC₅₀ value 64.21 ?μg/mL against liver cancer cell line. While the remaining metal complexes such as C2, C4 and C5 are moderately active with IC₅₀ value 314.93, 414.05 and 376.00 ?μg/mL respectively. The complexes C1 and C3 with IC₅₀ value ?> ?1000 ?μg/mL are inadequate to display anticancer activity against Hep G2. Our perception towards the presence of organic group in the main structural moiety of complex C6 which associated with di-hydroxy (-OH) substituent at 3 and 4-position found more potent than complex C2, C4 and C5 which associated with halo (-Cl) substituent. The MTT assay revealed that the cytotoxicity and anticancer activity enhanced upon coordination of bio-ligand compared to free chalcone ligands. Therefore the present study may lead to the development of new class of anticancer drugs with structural modification.     

Asymmetric synthesis and biological evaluation of 3-nitro-2H-chromenes as potential antibacterial agents

A one-pot organocatalytic domino Henry/Michael/dehydration sequence of various salicylaldehyde derivatives with nitromethane as a dual-nucleophile is disclosed. This straightforward strategy assembles the optically active (R)-2-alkyl 3-nitro-2H-chromenes with good to excellent enantioselectivities (up to 93% ee) and a broad substrate scope. Preliminary in vitro antibacterial evaluation revealed most of the chiral 3-nitro-2H-chromene derivatives exhibit antibacterial activities against four Gram-positive bacteria. Compound 3p with two bromine substituents on the core scaffold was shown to be the best antibacterial agent in the series against S. aureus, B. subtilis and Bacillus cereus with minimal bactericidal concentration (MBC) values of 4?μg/mL, and against Staphylococcus epidermidis with a MBC value of 8?μg/mL.     

Nematicidal quinone derivatives from three Rubia plants

Five new quinone derivatives, rubiasins D-F (1–3), rubialatones A and B (4 and 5), have been isolated from the roots and rhizomes of three Rubia species, Rubia alata, R. wallichiana and R. schumanniana, together with 26 known quinones (6–31). Their structures have been elucidated on the basis of NMR, MS spectra and computational methods. The compounds have been evaluated for their toxicity to the saprophytic nematode Caenorhabditis elegans and the root-knot nematode Meloidogyne incognita. Compounds 1, 6 and 7 showed toxicity to C. elegans with the LC₅₀ values at 8.50, 9.44 and 44.82?μg/mL, respectively; and 6 showed toxicity to M. incognita with the LC₅₀ value at 35.22?μg/mL. Meanwhile, compounds 1 and 6 showed inhibitory effect on egg hatch of C. elegans with the LC₅₀ values at 5.60 and 48.95?μg/mL.     

New bioactive pyrrospirones C−I from a marine-derived fungus Penicillium sp. ZZ380

Seven rare pyrrospirones C?I (1–7) as well as 18 known compounds were isolated from a marine-derived fungus Penicillium sp. ZZ380. Structures of the new pyrrospirones were elucidated by extensive NMR spectroscopic analyses, HRESIMS data, and Mosher's method. Pyrrospirone D (2) was also confirmed by X-ray diffraction analysis. Pyrrospirone G (5) showed potent activity in inhibiting the proliferation of different glioma cells with IC₅₀ values of 1.06–8.52 μM and pyrrospirones C (1), F (4), and I (7) had antimicrobial activity against the growth of both methicillin-resistant Staphylococcus aureus and Escherichia coli with MIC values of 2.0–5.0 μg/mL.     

Cage-like monoterpenoid indole alkaloids with antimicrobial activity from Alstonia scholaris

Three new cage-like monoterpenoid indole alkaloids, scholarisines T–V (1–3), together with three known analogues 4–6 were isolated from the leaves of Alstonia scholaris. Among them, 2 represents a unique degraded derivative, whereas 3 shares a rare 5,16-seco lactone scaffold. The structures were mainly established by extensive spectroscopic data analyses, and their plausible biosynthesis pathway from picrinine were proposed. Compared with positive control cefotaxime, alkaloid 2 showed remarkable antibacterial activity against Bacillus subtilis with an MIC value of 3.12?μg/mL, whereas 1–3 exhibited significant antibacterial effects on Escherichia coli with an MIC value of 0.78?μg/mL.     

Acylphloroglucinol derivatives from the twigs and leaves of Callistemon salignus

Three new acylphloroglucinol derivatives, callisalignones A–C (1–3), six new meroterpenoids, callisalignenes A–F (4–9), along with 18 known analogues (10–27) were isolated from the twigs and leaves of Callistemon salignus. Their structures and absolute configurations were established by comprehensive spectroscopic evidences (NMR, MS, amd electronic circular dichroism calculations). The absolute configurations of callistenones B (13) and H (14) were determined by comparison of their ECD spectra with that of callisalignone B (2). Callisalignones B and C are new adducts of β-triketone and acylphloroglucinol, whereas callisalignenes A–D are new meroterpenoids of acylphloroglucinol and α-phellandrene with different coupling models via hetero-Diels-Alder reaction, respectively. Myrtucommulone D (15) showed significant antibacterial activity against Staphylococcus aureus and three drug resistant S. aureus strains with MIC values of 1.953 and 0.975 μg/mL, respectively. Isomyrtucommulone B (17) displayed remarkable antibacterial activity against Escherichia coli with an MIC value of 0.122 μg/mL. Cytotoxic assay revealed that isomyrtucommulone B (17) was the most active against HCT116 with an IC₅₀ value of 2.09 ± 0.10 μM.     

Herbicidal activity and bioactive components of Brucea javanica (L.) Merr. residue

There are many nutrients and active substances in the residue of traditional Chinese medicine, which can be processed into organic fertilizer and returned to the field to improve the soil fertility. In this study, we found that Brucea javanica (L.) Merr. residue has herbicidal activity and can be used for weed control in the field, this prompted us to investigate the active constituents in it. The herbicidal activities of extracts of B. javanica residue were evaluated by conducting bioassays against gramineous weed, Eleusine indica (L.) Gaertn. and broad-leaved weed, Bidens pilosa L., respectively. It confirmed that ethyl acetate and n-butanol extracts possessed potent biological activities on seed germination and seedling growth of E. indica at 5 mg/mL. This prompted us to investigate the active constituents in the seeds residue. By the activity-guided fractionation, eight known compounds were isolated, which were bruceines D?F (1–3), pityriacitrin (4), 4-(9H-β-carbolin-1-yl)-4-oxobut-2-enoic acid methyl ester (5), protocatechuic acid (6), vanillic acid (7) and carisphthalate (8). Then, three quassinoids (1–3) were evaluated for their potential herbicidal effects in bioassay. Results showed that bruceines D?F have potential herbicidal activity against the test weeds. In the range of experimental concentration, bruceine D had obvious herbicidal effect on the two tested weeds. At the concentration of 31.25 μg/mL, bruceine D could completely inhibit the root growth of E. indica; at the concentration of 125 μg/mL, bruceine D can inhibit the seed germination and shoot elongation of E. indica and the shoot growth of B. pilosa, with the inhibition reached 100%. In addition, at the same concentration (250 μg/mL), bruceines D?F could completely affected shoot elongation of B. pilosa. These results showed that B. javanica residue is a potential source of botanical herbicide development, which has great agricultural economic value, at the same time, the reuse of B. javanica residue realizes the transformation of waste into treasure, rational utilization of resources and sustainable development.     

Ultrasound assisted,VOSO4 catalyzed synthesis of 4-thiazolidinones: Antimicrobial evaluation of indazole-4-thiazolidinone derivatives

A simple and expedient multicomponent protocol was developed to synthesize 4-thiazolidinones by employing VOSO₄ as a catalyst under ultrasonic irradiation. The significant features of this protocol includes shorter reaction time, high yields, low catalyst loading, and also the catalyst can be recovered and reused up to next four cycles without significant loss in catalytic activity. All the synthesized novel indazole compounds were evaluated for their antibacterial and anti-biofilm activities. Compounds 9n, 9o and 9q showed promising activity (MIC value of 3.9?µg/mL) against K. planticola (MTCC 530). They also exhibited significant bactericidal activity against K. planticola (MTCC 530) (MBC value of 15.6?µg/mL). Additionally, 9n, 9o and 9q inhibited biofilm formation (IC₅₀ values ranging between 20.28–20.79?μg/mL) in this organism.     

N-Hydroxypyridone alkaloids,chromone derivatives,and tetrahydroxanthones from the scale-insect pathogenic fungus Orbiocrella sp. BCC 33248

Six new compounds, an N-hydroxypyridone glucoside, orbiocrellin A (1), its aglycone orbiocrellin B (2), chromone glucosides 3 and 4, a dihydrochromone 5a/5b, and a chromone 6, were isolated from the scale-insect pathogenic fungus Orbiocrella sp. BCC 33248. Orbiocrellin A (1) exhibited antimalarial activity against Plasmodium falciparum K1 (IC₅₀ 3.1 μg/mL) while it was non-cytotoxic. In contrast, orbiocrellin B (2) showed both antimalarial (IC₅₀ 2.1 μg/mL) and cytotoxic (NCI-H187 cells, IC₅₀ 0.70 μg/mL) activities.     

Confluenines A–F, N-oxidized l-isoleucine derivatives from the edible mushroom Albatrellus confluens

The phytochemical study of the fruiting bodies of Albatrellus confluens afforded three pairs of new N-Oxidized l-Isoleucine derivatives epimers, confluenines A–F (1–6). The structures of these compounds were deduced using spectroscopic techniques, and the absolute configurations of the compounds were assigned by comparison between experimental and theoretical NMR and ECD data, respectively. Putative biosynthetic pathways toward the oxime, hydroxamate moieties and epimers were discussed. Compounds 5 and 6 exhibited weak antimicrobial activities against Staphylococcus aureus with MIC₉₀ values at 29.3?μg/mL and 56.7?μg/mL, respectively.     

Bioactive polyketides from the sea fan-derived fungus Penicillium citrinum PSU-F51

Five new polyketides including two benzopyranones (1 and 2), one isochroman (3) and two anthraquinone-citrinin derivatives (4 and 5) were isolated from the sea fan-derived fungus Penicillium citrinum PSU-F51 together with thirteen known compounds. The structures were determined by spectroscopic methods. The anthraquinone-citrinin derivatives are rare natural products. Compound 4 displayed moderate antibacterial activity against both Staphylococcus aureus and methicillin-resistant S. aureus with equal MIC values of 16 μg/mL, while the known coniochaetone A displayed moderate antifungal activity against Candida albicans with MIC value of 16 μg/mL.     

Synthesis and biological evaluation of 1,4-pentadien-3-one derivatives containing 1,2,4-triazole

A series of new 1,4-pentadien-3-one derivatives containing 1,2,4-triazole moiety were synthesized. The structures of the synthesized compounds were charactered via ¹H NMR, ¹³C NMR and HRMS. Antibacterial bioassays indicated that some of compounds showed potential antibacterial activities against Ralstonia solanacearum (Rs), Xanthomonas oryzae pv. Oryzae (Xoo) and Xanthomonas axonopodis pv. Citri (Xac). Compounds F₈ and F₁₇ showed good in vitro antibacterial activities against Rs, with the EC₅₀ values of 18.6 and 18.6 μg/mL, respectively, which were better than commercial agent bismerthiazol (55.2 μg/mL). Furthermore, compounds F₁₂ and F₁₅ showed good in vitro antibacterial activities against Xoo, with the EC₅₀ values of 10.9 and 17.5 μg/mL, which were better than commercial agent bismerthiazol (69.3 μg/mL). Moreover, compounds F₂, F₉, F₁₆ and F₁₇ showed good in vitro antibacterial activities against Xac, with the EC₅₀ values of 6.6, 5.4, 7.5 and 7.8 μg/mL, respectively, which were better than commercial agent bismerthiazol (54.9 μg/mL). The effect of compound F₉ on Xac bacterial cell membrane rupture was observed by scanning electron microscopy (SEM). In addition, antiviral bioassays indicated that some of compounds showed excellent protection activities against tobacco mosaic virus (TMV). Compounds F₅ and F₁₅ showed good protecting activity against TMV, with the EC₅₀ values of 108.3 and 105.4 μg/mL, respectively, which were better than commercial agent ningnanmycin (214.7 μg/mL). Microscale thermophoresis (MST) also showed that the binding of compound F₂ to TMV coat protein (TMV-CP) yielded a Kd value of 1.260 ± 0.654 μmol/L, which was very close to ningnanmycin (1.058 ± 0.286 μmol/L). Similarly, the molecular docking studies for F₂ and F₅ with TMV-CP (PDB code: 1EI7, ID: 4QGH) indicated that compounds F₂ and F₅ had partially interacted with TMV-CP.     

Antimalarial and antituberculosis substances from Streptomyces sp. BCC26924

Two new carbazomycin dimers (6 and 7) and 3-hydroxy-1,2-dimethyl-2,3-dihydro-1H-carbazol-4-one (9) together with six known compounds, carbazomycins A-D, cyclomarin C, and pimprinine have been isolated from Streptomyces sp. BCC26924. Carbazomycins B, C, and cyclomarin C exhibited antimalarial activity (against Plasmodium falciparum, K1 multi-drug resistant strain) with IC₅₀ in a range of 0.24-2.37 μg/mL. Cyclomarin C exhibited anti-TB activity with a minimum inhibitory concentration value of 0.10 μg/mL, while carbazomycin D, compound 7, and pimprinine displayed MIC values in a range of 12.5-25.0 μg/mL. In addition, compounds 2, 5, 6, and 7 showed weak cytotoxicity against cancerous (MCF-7, KB, NCI-H187) and non-cancerous (Vero) cells.     

Modiolin and phthalide derivatives from the endophytic fungus Microsphaeropsis arundinis PSU-G18

One new modiolin, microsphaerodiolin (1), and seven new phthalides, microsphaerophthalides A-G (2-8), together with 12 known compounds were isolated from the endophytic fungus Microsphaeropsis arundinis PSU-G18. Their structures were elucidated by spectroscopic methods. The new 3-oxygenated phthalides are rare natural products. The known 1-(2,5-dihydroxyphenyl)-2-buten-1-one exhibited significant antifungal activity against Microsporum gypseum SH-MU-4 with an MIC value of 8 μg/mL, moderate antimalarial activity with an IC₅₀ value of 9.63 μg/mL and strong radical scavenging potency with the IC₅₀ value of 0.018 mg/mL. The new compounds 2 and 6 showed moderately antifungal activity against M. gypseum SH-MU-4 and Cryptococcus neoformans, respectively, with equal MIC values of 64 μg/mL.     

Alkaloids from the roots of Stemona tuberosa and their anti-tobacco mosaic virus activities

Stemtuberlines A (1) and B (2), two new alkaloids with a unique tricyclic pyrrolo [3,2,1-jk]benzazepine-12-one nucleus, three new croomine-type alkaloids, stemtuberlines C-E (3–5), together with seven known ones were isolated from the roots of Stemona tuberosa. The structures of the new alkaloids were elucidated based on a comprehensive spectroscopic data analysis. The absolute configurations of 1 and 2 were determined by quantum ECD calculations. The anti-tobacco mosaic virus activity of the Stemona alkaloids was firstly evaluated and compound 11 exhibited significant anti-tobacco mosaic virus activity with the curative inhibition rate of 84.6% at concentration of 50?μg/mL.     

Synthesis and antiviral bioactivity of novel chalcone derivatives containing purine moiety

A series of novel chalcone derivatives containing purine group was synthesized and evaluated for their antiviral activities against cucumber mosaic virus and tobacco mosaic virus. Compound 3o exhibited remarkable antiviral activities and strong combining capacity to tobacco mosaic virus coat protein.     

Antimalarial 20-membered macrolides from Streptomyces sp. BCC33756

Two new natural products, samroiyotmycins A (1) and B (2), along with two naturally new novclobiocin 101 (3) and 4-hydroxy-3-(3-methylbut-2-enyl)benzamide (5), and five known substances including neoantimycin, clorobiocin (4), 29-O-methylabierixin, daidzein, and 1-(3-indolyl)-2,3-dihydroxypropan-1-one have been isolated from Streptomyces sp. BCC33756. Their chemical structures were determined based on NMR spectral information and the relative stereochemistry of compound 1 was determined by X-ray crystallographic data. Both samroiyotmycins A and B exhibited antimalarial activity against Plasmodium falciparum K1—multi-drug resistant strain, with IC₅₀ values of 3.65 and 3.16 μg/mL, respectively. Compound 1 was inactive against both cancerous (MCF-7, KB) and non-cancerous (Vero) cells, while compound 2 displayed cytotoxicity against Vero cell with IC₅₀ value of 29.57 μg/mL.     

Zyzzyanone A, a novel pyrrolo[3,2-f]indole alkaloid from the Australian marine sponge Zyzzya fuliginosa

A new dipyrroloquinone, zyzzyanone A 1, having a pyrrolo[3,2-f]indole-4,8(1H,7H)-dione skeleton, was isolated from the Australian marine sponge Zyzzya fuliginosa, along with the known pyrroloquinoline alkaloids, makaluvamines C, E, G, H, and L, and damirones A and B. The structure of 1 was determined by spectroscopic data. Zyzzyanone A 1 shows moderate cytotoxic activity against mouse Ehrlich carcinoma cells (IC₅₀ 25 μg/mL), inhibits the cell division of fertilized sea urchin eggs at a concentration of 25 μg/mL, and exhibits UV-A and UV-B absorbing activity.     

Dihydroanthracenone metabolites from the endophytic fungus Diaporthe melonis isolated from Annona squamosa

Chemical investigation of the endophytic fungus Diaporthe melonis, isolated from Annona squamosa, yielded two new dihydroanthracenone atropodiastereomers, diaporthemins A (1) and B (2), together with the known flavomannin-6,6′-di-O-methyl ether (3). The structures of the new compounds were established on the basis of extensive 1D and 2D NMR spectroscopy, as well as by high resolution mass spectrometry and by CD spectroscopy. Compounds 1–3 were tested for their antimicrobial activity against a multi-resistant clinical isolate of Staphylococcus aureus 25697, a susceptible reference strain of S. aureus ATCC 29213 and against Streptococcus pneumoniae ATCC 49619. Compound 3 strongly inhibited S. pneumonia growth with a MIC value of 2 μg/mL, and showed moderate activity against the S. aureus multi-resistant clinical isolate and susceptible reference strain (MIC 32 μg/mL), whereas 1 and 2 were not active against the tested strains.