Pestalofones A–E,bioactive cyclohexanone derivatives from the plant endophytic fungus Pestalotiopsis fici

Pestalofones A–E (1–5), five new cyclohexanone derivatives, have been isolated from cultures of the plant endophytic fungus Pestalotiopsis fici, along with the known compounds, isosulochrin (6), isosulochrin dehydrate (7), and iso-A82775C (8). The structures of 1–5 were determined by NMR spectroscopy, and the absolute configuration of 1 was assigned using the modified Mosher method. Compounds 1, 2, and 5 displayed inhibitory effects on HIV-1 replication in C8166 cells, whereas 3 and 5 showed significant antifungal activity against Aspergillus fumigatus.     

A novel prenylated C6–C3 compound with estrogen-like activity from the fruits of Illicium arborescens

A novel C₆–C₃ prenylated compound, illicarborene A (1), together with illioliganfunone D (2), 1-allyl-3,5-dimethoxy-4-(3-methylbut-2-enyloxy)benzene (3), (?)-illicinone A (4), (?)-illicinone B (5) and (?)-illicinone A derivative (6) was isolated and characterized from the fruits of Illicium arborescens Hayata. Compound 1 possesses a new class of tricyclic 6/6/5 ring system. The structure of 1 was determined by spectroscopic analysis such as ¹H–¹H COSY, HMQC, HMBC, and NOESY, and confirmed by chemical reaction to yield 7. Compounds 1–5 were found to increase proliferative activity in primary cell culture of osteoblast cells.     

Phenol derivatives from the cold-seep fungus Aspergillus sydowii 10–31

Two bisabolane-type sesquiterpenoid phenols inclusive of the known (7 S)-flavilane A (1) and the new (7 S)− 4-iodo-flavilane A (2), along with a new tetraphenyl ether, bisviolaceol II (3), were isolated from the cold-seep fungus Aspergillus sydowii 10–31. Their structures were identified through spectroscopic methods, such as MS, IR, and NMR, and the absolute configurations of 1 and 2 were ascertained by comparison of ECD curves. Compounds 1 and 2 represent rarely encountered sulfur-bearing sesquiterpenes in nature, and the iodination in 2 makes it unique in particular. Additionally, 3 is the first tetraphenyl ether derivative from the fungal species A. sydowii. Compounds 1-3 inhibited the growth of several Vibrio bacteria and harmful microalgae.     

Design,synthesis, antimicrobial activity and anti-HIV activity evaluation of novel hybrid quinazoline–triazine derivatives

Abstract

A series of novel hybrid quinazoline–triazine derivatives was designed and synthesized from cyanuric chloride and anthranilic acid through sequential reactions, which contain different pharmacophores like quinazoline and substituted diaryl triazine (DATA) linked with ethylene diamine. All the newly synthesized compounds were characterized by infrared, ¹H-NMR, ¹³C-NMR, MS and elemental analysis. Further, we evaluated the in vitro anti-HIV activity of the newly synthesized compounds against HIV-1 (III_B) and HIV-2 (ROD) viral strains and as well as in vitro antimicrobial activity against four bacteria (Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, Klebsiella pneumoniae) and two fungi (Aspergillus clavatus, Candida albicans) using the paper agar streak dilution method. The bioassay results indicate that four compounds namely 7d, 7n, 7r and 7s could be considered as possible potential agents.     

Antrodiellins A‒C,triquinane sesquiterpenoids from fungus Antrodiella albocinnamomea with their antibacterial activity

Three previously undescribed triquinane type sesquiterpenoids, antrodiellins A‒C (1‒3), together with three known analogues 4‒6, were isolated from wild fungus Antrodiella albocinnamomea. Their structures were elucidated by means of spectroscopic analysis and single crystal X-ray diffraction. Compounds 3 and 4 exhibited weak inhibitions against Staphylococcus aureus with MIC values of 128 and 64 μg/mL, respectively.     

Asperidines A–C,pyrrolidine and piperidine derivatives from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178

One new pyrrolidine derivative, asperidine A (1), and two new piperidine derivatives, asperidines B (2) and C (3), were isolated from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178 together with two known alkaloids. Compound 3 possessed an unprecedented 7-oxa-1-azabicyclo[3.2.1]octane skeleton with four chiral centers. Their structures were determined by spectroscopic evidence. The absolute configurations of compounds 2 and 3 were established using Mosher’s method and further confirmed for compound 3 by X-ray crystallographic data. Compound 2 dose-dependently inhibited the CFTR-mediated chloride secretion in T84 cells with an IC₅₀ value of 0.96?μM whereas 3 displayed the same activity with the IC₅₀ value of 58.62?μM. Compounds 2 and 3 also significantly reduced intracellular ROS under both normal and H₂O₂-treated conditions compared with their respective controls in a dose-dependent manner without cytotoxic effect on Caco-2 cells. In addition, compound 3 was inactive against noncancerous Vero cells whereas compound 2 was considered to be inactive with the IC₅₀ value of >10?μM.     

Sinopestalotiollides A–D,cytotoxic diphenyl ether derivatives from plant endophytic fungus Pestalotiopsis palmarum

Four new diphenyl ether derivatives, sinopestalotiollides A–D (1–4), one new natural α-pyrone product (11), as well as twelve known compounds (5–1?7), were obtained from the ethyl acetate extract of the endophytic fungus Pestalotiopsis palmarum isolated from the leaves of medicinal plant Sinomenium acutum (Thunb.) Rehd et Wils. The structures were elucidated by HR-ESI-MS and NMR spectrometry data. Bioassay experiments revealed that compounds 1–4 and 11 exhibited strong to weak cytotoxicities against three human tumor cell lines Hela, HCT116 and A549.     

α-Pyrone derivatives from the endolichenic fungus Nectria sp.

Five new α-pyrone derivatives, necpyrones A–E (1–5), together with seven known compounds (6–12), were isolated from the extract of an endolichenic fungus Nectria sp. Chemical structures of these compounds were elucidated by spectroscopic analyses (HRESIMS and NMR). The absolute configurations of C-6 in the pyrone ring as well as the chiral carbons at the aliphatic side chain resulted from hydroxyl substitute were finally determined on the basis of measurement of ECD and Kusumi–Mosher method.     

Trichocarotins A–H and trichocadinin A,nine sesquiterpenes from the marine-alga-epiphytic fungus Trichoderma virens

In addition to CAF-603, 14-hydroxy CAF-603 (trichocarane B), 7-β-hydroxy CAF-603, and trichocarane A, eight new carotane sesquiterpenes, trichocarotins A–H, and one new cadinane sesquiterpene, trichocadinin A, were isolated from the culture of Trichoderma virens Y13-3, obtained from the surface of a marine red alga. Their structures and relative configurations were unambiguously assigned by interpretation of 1D/2D NMR and MS data, and their absolute configurations were established by X-ray diffraction or ECD spectra aided by quantum chemical calculations. These compounds represent two rarely occurring sesquiterpene types from filamentous fungi, and six of them feature potent inhibition against some marine plankton species.     

Calofolic acids A–F,chromanones from the bark of Calophyllum scriblitifolium with vasorelaxation activity

Vasorelaxation activity guided separation of the methanol extract of Calophyllum scriblitifolium bark led to the isolation of 6 chromanones (calofolic acids A–F, 1–6). Their structures were elucidated by 1D and 2D NMR spectroscopy, and their absolute configurations were investigated by a combination of CD spectroscopy and DFT calculation. All isolated chromanones showed dose-dependent vasorelaxation activity on isolated rat aorta.     

Hyperpatulols A–I,spirocyclic acylphloroglucinol derivatives with anti-migration activities from the flowers of Hypericum patulum

Nine new spirocyclic acylphloroglucinol derivatives, hyperpatulols A–I (1–9), were characterized from the flowers of Hypericum patulum. Their structures were elucidated by the basic analysis of the obtained spectroscopic data, and their absolute configurations were assigned by both the electronic circular dichroism (ECD) exciton chirality method and ECD calculation. The evaluation of their anti-migration effects on U2-OS human osteosarcoma cells showed that compound 4 exhibited moderate inhibitory activity in a dose-dependent manner. Further pharmacological studies revealed that 4 could regulate the expression of the proteins Vimentin and E-cadherin.     

(±)-Meliviticines A and B: Rearranged prenylated acetophenone derivatives from Melicope viticina and their antimicrobial activity

Two new prenylated acetophenone derivatives racemates, meliviticines A (1) and B (2) with unprecedented rearranged skeletons, were isolated from Melicope viticina. Subsequent chiral resolution led to the separation of two pairs of enantiomers, (±)-meliviticines A (1a/1b) and (±)-meliviticines B (2a/2b). Their structures including absolute configurations were elucidated by extensive spectroscopic data, electronic circular dichroism analysis, and X-ray crystallography. A plausible biosynthetic pathway of 1 and 2, involving ring cleavage and rearrangement of the prenylated acetophenone backbone was proposed. All the isolates showed moderate antimicrobial activities with MIC values of 25–50 μg/mL against several bacterial and fungal strains.     

α-Pyrone derivatives with cytotoxic activities,from the endophytic fungus Phoma sp. YN02-P-3

Four new α-pyrone derivatives phomones C-F (1?4) together with four known compounds (5?8) were isolated from the endophytic fungus Phoma sp. YN02-P-3. Compound 1 is the first example of 6-α,β-unsaturated ester-2-pyrone dimers via intermolecular symmetrical [2 + 2] cycloaddition. The chemical structures of these compounds were determined from spectroscopic data (1D/2D NMR, MS and IR). The acetylated product (9) of 1 along with compounds 1–8 were then tested for their cytotoxicity against HL-60, PC-3 and HCT-116 cell lines. Compounds 2, 3, 5 and 9 with acetyl groups showed significant inhibitory activities against the three cell lines with IC₅₀ values in the range 0.52–9.85 μM. while compounds 1, 4 and 6–8 that possess no acetyl group showed no inhibitory activity (IC₅₀ > 50 μM), indicating that the acetyl group at 10- or 12- are essential for their cytotoxic activities. The structure-activity relationships of these phomones were also reported.     

β-Resorcylic acid derivatives with α-glucosidase inhibitory activity from Lasiodiplodia sp. ZJ-HQ1, an endophytic fungus in the medicinal plant Acanthus ilicifolius

Three new β-resorcylic acid derivatives, compounds 1–3, along with six known analogues (4–9) were isolated from an endophytic fungus Lasiodiplodia sp. ZJ-HQ₁ derived from medicinal plant Acanthus ilicifolius. Their structures were elucidated by 1D and 2D NMR spectroscopic analysis, high resolution mass spectrometric (HREIMS) data, and X-ray crystallography. The absolute configurations of compounds 1 and 2 were determined by the modified Mosher’s method. Compounds 1–7 showed more potent inhibitory effects against α-glucosidase activity than the clinical α-glucosidase inhibitor acarbose.     

Globostelletins A–I,cytotoxic isomalabaricane derivatives from the marine sponge Rhabdastrella globostellata

Nine new isomalabaricane-derived natural products, globostelletins A–I (1–9), were isolated from the marine sponge Rhabdastrella globostellata, together with jaspolides F (10), rhabdastrellic acid-A (11), (?)-stellettin E (12), stellettins C (13) and D (14). The structures of these compounds were determined on the basis of extensive spectroscopic analyses and by comparison with the reported data in the literature. The inhibitory activities of compounds 1–12 against human tumor cell lines were evaluated, and their structure–activity relationships were discussed. In addition, rhabdastrellic acid-A (11) showed potent inhibition against HL-60 cells, and it induced the apoptosis of HL-60 cells in M/G2 phase. The mechanism of 11 targeting the ubiquitin-proteasome system, including the regulation of ChT-L and T-L target proteins is discussed.     

Structure–activity relationship study of phenylpyrazole derivatives as a novel class of anti-HIV agents

The structure–activity relationship of phenylpyrazole derivative 1 was investigated for the development of novel anti-HIV agents. Initial efforts revealed that the diazenyl group can be replaced by an aminomethylene group. In addition, we synthesized various derivatives by the reductive amination of benzaldehydes with 5-aminopyrazoles and carried out parallel structural optimization on the benzyl group and the pyrazole ring. This optimization led to a six-fold more potent derivative 32j than the lead compound 1, and this derivative has a 3′,4′-dichloro-(1,1′-biphenyl)-3-yl group.     

Baculiferins A–O,O-sulfated pyrrole alkaloids with anti-HIV-1 activity,from the Chinese marine sponge Iotrochota baculifera

Fifteen new DOPA-derived pyrrole alkaloids, named baculiferins A–O (2–16), were isolated from the Chinese marine sponge Iotrochota baculifera, together with the known alkaloids purpurone (1) and ningalin A (17). Most of the new compounds contain one to three O-sulfate units. Their structures were determined by extensive spectroscopic analysis including ¹H and ¹³C NMR (COSY, HMQC, HMBC) and ESIMS data. A possible pathway for the biosynthetic origin of the isolated alkaloids is proposed, in which DOPA is assumed to be a joint biogenetic precursor. Baculiferins C, E–H, and K–N (4, 6–9, 12–15) were found to be potent inhibitors against the HIV-1 IIIB virus in both, MT4 and MAGI cells. Additional bioassay revealed that baculiferins could dramatically bind to the HIV-1 target proteins Vif, APOBEC3G, and gp41, for which structure–activity relationships are discussed.     

Purpuroines A–J,halogenated alkaloids from the sponge Iotrochota purpurea with antibiotic activity and regulation of tyrosine kinases

Ten new halogenated alkaloids named purpuroines A–J (1–10), and a known analogue (11), were isolated from the marine sponge Iotrochota purpurea. Their structures were elucidated by extensive spectroscopic (IR, MS, 1D and 2D NMR) data analyses. The inhibitory activity of some compounds against a panel of human disease related fungi and bacteria are evaluated. Bioassay for the regulation of tyrosine kinases revealed compounds 1 and 4 possessing selective inhibition against the kinase LCK. Primary structure–activity relationship is discussed.     

Gynostemosides A–E,megastigmane glycosides from Gynostemma pentaphyllum

Megastigmane glycosides (1–5) together with seven (6–12) related known compounds were isolated from the whole plants of Gynostemma pentaphyllum. The structures were elucidated by means of spectroscopic methods, including 2D NMR, HR-ESIMS, and circular dichroism (CD), as well as chemical transformations to be (3R, 4R, 5S, 6S, 7E)-3,4,6-trihydroxymegastigmane-7-en-9-one-3-O-β-d-glucopyranoside (gynostemoside A, 1), (3S, 4S, 5R, 6R, 7E, 9R)-3,4,6,9-tetrahydroxymegastigmane-7-en-3-O-β-d-glucopyranoside (gynostemoside B, 2), (3S, 4S, 5S, 6S, 7E, 9R)-3,4,9-trihydroxymegastigmane-7-en-9-O-β-d-glucopyranoside (gynostemoside C, 3), (3S, 4S, 5S, 6S, 7E, 9R)-3,4,9-trihydroxymegastigmane-7-en-3-O-β-d-glucopyranoside (gynostemoside D, 4), and (3S, 4S, 5S, 6S, 7E, 9R)-3,4,9-trihydroxymegastigmane-7-en-4-O-β-d-glucopyranoside (gynostemoside E, 5), respectively.