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Five acylation derivatives ( 1a- 1e) were prepared by acylation of the bioactive natural product hypoxylin A ( 1) isolated from Halorosellinia oceanicum. Compounds 1a and 1b were epimers with the configuration inversion of C-10 in 1b. Hypoxylin A ( 1) and 1a- 1e exhibited potent lethal activity toward the brine shrimp Artemia salina. Hypoxylin A ( 1) also showed cytotoxicity against tumor cell line A549 with an IC value of 5.6 μg/mL. The antibacterial activities of these compounds were also evaluated, and none of them were active. [ABSTRACT FROM AUTHOR]

Five pairs of new dihydroisocoumarin enantiomers, (±)-eurotiumides A–E, and two related racemates, (±)-eurotiumides F and G, were isolated from a gorgonian-derived fungus, Eurotium sp. XS-200900E6. The enantiomeric separations for (±)-eurotiumides A–E were achieved by chiral-HPLC, and their absolute configurations were determined by ECD spectra. All of the isolated compounds are rare dihydroisocoumarin derivatives with a methoxy at C-4. (+)- And (−)-eurotiumides B and D with cis configurations of H-3/H-4 exhibited potent antifouling activities against the larval settlement of the barnacle Balanus amphitrite with the EC 50 values ranging from 0.7 to 2.3 μg/mL, and displayed high therapeutic ratios (LC 50 /EC 50 >15). The tested compounds also showed extensive antibacterial activities. It was the first report of antifouling activities for dihydroisocoumarin derivatives. [ABSTRACT FROM AUTHOR]

One new anthraquinone derivative, named 8-O-methylnidurufin ( 1), together with five known analogues ( 2- 6), have been isolated from a gorgonian-derived fungus, Aspergillus sp. The structures were elucidated by combined spectroscopic methods including 1D and 2D NMR spectral data. All isolated metabolites were evaluated for their cytotoxic and antibacterial activities in vitro. Compound 2 showed significant cytotoxic activity against K562 and HL-60 cell lines with IC values of 0.87 and 1.46 μM, respectively. [ABSTRACT FROM AUTHOR]

Two new polyhydroxylated sterols, named verumbsteroids A and B ( 1 and 2, resp.), along with seven known analog, 3- 9, were isolated from the gorgonian Verrucella umbraculum collected from the South China Sea. The structures and relative configurations of the new compounds were elucidated by comprehensive spectroscopic investigations. The absolute configuration of 1 was determined by using modified Mosher method with the acetonide derivative of 1. Compounds 1 and 3- 5 were found to show cytotoxicities against five human tumor cell lines (HL-60, K562, HeLa, A-549, and HCT-116) with the IC50 values ranging from 2.76 to 9.62 μ M. [ABSTRACT FROM AUTHOR]

The article presents a study which investigates the secondary metabolites and chemical constituents of Subergorgia mollis from South China Sea. The study used column chromatography and semi-preparative high performance liquid chromatography (HPLC). Results show that through isolation, 10 compounds have showed antifouling activity including four rare 24-ketal steroids, three briarane-type diterpenoids, and three common steroids.

Abstract: Three new phenolic bisabolane sesquiterpenoid dimers, disydonols A–C (1–3), and one known compound (S)-(+)-sydonol (4) were isolated from the fermentation broth of a marine-derived fungus Aspergillus sp., which was isolated from the sponge Xestospongia testudinaria collected from the South China Sea. Their structures were elucidated on the basis of comprehensive spectral analysis including 1D and 2D NMR spectra and HR-ESI-MS. These compounds were evaluated for cytotoxic activity against HepG-2 and Caski human tumour cell lines. Among them, compounds 1 and 3 exhibited cytotoxicity against the two cell lines. [Copyright &y& Elsevier]

Abstract: Two novel benzylazaphilone derivatives with an unprecedented carbon skeleton, aspergilone A (1), and its symmetrical dimer with a unique methylene bridge, aspergilone B (2), have been isolated from the culture broth of a marine-derived fungus Aspergillus sp. from a gorgonian Dichotella gemmacea. Their structures and relative stereochemistries of 1 and 2 were elucidated using a combination of NMR spectroscopy and X-ray crystallography. Compound 1 not only exhibited in vitro selective cytotoxicity but also showed potent antifouling activity. [ABSTRACT FROM AUTHOR]

A novel nitro-phenyl glucoside (1) was isolated from mangrove endophytic fungus (fungus B60), collected from the Shenzhen mangrove Acanthus ilicifolius linn. Four related nitro-phenyl compounds (2-5) were also obtained, which were isolated for the first time as natural products. Their structures were established on the basis of NMR spectroscopic, mass spectrometric data and some chemical transformations. In the preliminary bioassay, compound 1 had a slight inhibitory effect on α-glucosidase with an IC50 of 160.3 μM. [ABSTRACT FROM AUTHOR]

The article offers information on sesquiterpene derivates and steroids from the sponges of Dactylospongia elegans, which is widely studied for their biologically active compounds, from the South China Sea. It is noted that sesquiterpene quinones and its derivatives constitute cytotoxic natural products from sponges. Some of these derivatives are Dactyltronic Acids, Polyfibrospongol A and Dictyoceratin C.

The article presents information on the bioactive steroids from a marine-derived fungus penicillium sp. from the South China Sea. Topics discussed include marine organisms as the source of steroids, bioactive secondary metabolites from marine fungi in the South China Sea, and K562 chronic leukemia cell line.

Nigrosporins B, an anthraquinone derivative obtained from the secondary metabolites of marine fungus Nigrospora oryzae. In this study, we characterized the distinctive anti-cancer potential of Nigrosporins B in vitro and underlying molecular mechanisms in human cervical cancer Ca Ski cells for the first time. The results of MTT assay showed that Nigrosporins B significantly inhibited the proliferation of multiple tumor cells in a dose-dependent manner, especially for the Ca Ski cells with an IC50 of 1.24 µM. Nigrosporins B exerted an apoptosis induction effect on Ca Ski cells as confirmed by flow cytometry, AO/EB dual fluorescence staining, mitochondrial membrane potential analysis and western blot assay. In addition, Nigrosporins B induced obvious autophagy accompanied with the increase of autophagic vacuoles and the acceleration of autophagic flux as indicated by Cyto-ID staining, mRFP-GFP-LC3 adenovirus transfection and western blot analysis. Interestingly, the combination of Nigrosporins B with the three autophagy inhibitors all significantly enhanced the cytotoxicity of Nigrosporins B on Ca Ski cells, indicating that the autophagy induced by Nigrosporins B might protect Ca Ski cells from death. Furthermore, we found that Nigrosporins B inhibited the phosphorylation of PI3K, AKT, mTOR molecules and increased the protein expression levels of PTEN and p-AMPKα in a dose-dependent manner, suggesting that Nigrosporins B induced apoptosis and protective autophagy through the suppression of the PI3K/AKT/mTOR signaling pathway. Together, these findings revealed the anti-cervical cancer effect of Nigrosporins B and the underlying mechanism of action in Ca Ski cells, it might be as a promising alternative therapeutic agent for human cervical cancer. [ABSTRACT FROM AUTHOR]

The article presents a study which investigates the bioactive compounds from Scleronephthya specie, a soft coral from the South China Sea. The study performed the isolation of nine steroids from the EtOH extract including six cholesterol derivatives and three ergosterol derivatives. The result of the study shows that a potent lethal activity was exhibited by all steroids against brime shrimp Artemia salina.

Abstract: A new pyrrolyl 4-quinolinone alkaloid with an unprecedented ring system, named penicinoline (1) was isolated from a mangrove endophytic fungus. The structure of 1 was elucidated by spectroscopic methods and comparison with its derivative, penicinotam (1a), an unexpected lactam that was obtained from 1 by intramolecular dehydration. The structure of 1a was unambiguously confirmed by single-crystal X-ray analysis. Penicinoline (1) showed potent in vitro cytotoxicity toward 95-D and HepG2 cell lines with IC50 values of 0.57 and 6.5μg/mL, respectively. [Copyright &y& Elsevier]

isolation, structure elucidation and biological activities of a new merosesquiterpenoid, craterellin D (I), its analogue craterellin A, and five known ten-membered macrolides [ABSTRACT FROM AUTHOR]

New brominated title compounds (I) are isolated together with four known non-brominated analogues. [ABSTRACT FROM AUTHOR]

Aspergillus terreus is well-known for its ability to biosynthesize valuable pharmaceuticals as well as structurally unique secondary metabolites. However, numerous promising cryptic secondary metabolites in this strain regulated by silent gene clusters remain unidentified. In this study, to further explore the secondary metabolite potential of A. terreus, the essential histone deacetylase hdaA gene was deleted in the marine-derived A. terreus RA2905. The results showed that HdaA plays a vital and negative regulatory role in both conidiation and secondary metabolism. Loss of HdaA in A. terreus RA2905 not only resulted in the improvement in butyrolactone production, but also activated the biosynthesis of new azaphilone derivatives. After scaled fermentation, two new azaphilones, asperterilones A and B (1 and 2), were isolated from ΔhdaA mutant. The planar structures of compounds 1 and 2 were undoubtedly characterized by NMR spectroscopy and mass spectrometry analysis. Their absolute configurations were assigned by circular dichroism spectra analysis and proposed biosynthesis pathway. Compounds 1 and 2 displayed moderate anti-Candida activities with the MIC values ranging from 18.0 to 47.9 μM, and compound 1 exhibited significant cytotoxic activity against human breast cancer cell line MDA-MB-231. This study provides novel evidence that hdaA plays essential and global roles in repressing secondary metabolite gene expression in fungi, and its deletion represents an efficient strategy to mine new compounds from A. terreus and other available marine-derived fungi. [ABSTRACT FROM AUTHOR]

Natural products are well established as an important resource and play an important role in drug discovery. Here, two pyrrolinone-fused benzoazepine alkaloids, (+)-asperazepanones A (1) and B (2) with a 6/7/5 ring system, together with the artifact (−)-asperazepanone A (1), were isolated from the coral-derived Aspergillus candidus fungus. Their structures including absolute configurations were elucidated by extensive spectroscopic methods, single crystal X-ray diffraction, and ECD calculations. Furthermore, total syntheses of (±)-1 and (±)-2 have been achieved starting from the commercially L-aspartic acid diethyl ester hydrochloride and monoethyl malonate in 7 and 8 steps, respectively. The key step in the syntheses was an intramolecular Friedel-Crafts reaction to build the unique tricyclic skeleton. Interestingly, (+)-2 not only showed obviously inhibitory activity against NO production, but also inhibited potent LPS-induced expression of TNF-α and IL-6 at the concentration of 0.1 μM. It thus represents a potentially promising lead for anti-inflammatory drug discovery. Benzoazepine is a well-known pharmacophore presented in several marketed drugs. Here, the authors report the isolation and total syntheses of asperazepanones A and B from coral-derived Aspergillus candidus, two novel pyrrolinone-fused benzoazepine alkaloids with potent anti-inflammatory activities. [ABSTRACT FROM AUTHOR]

Twelve new 9,10-secosteroids designated as subergorgiaols A–L ( 1 – 12 ), along with four known analogues ( 13 – 16 ), were isolated from the gorgonian Subergorgia rubra collected from the South China Sea . Their planar structures and the relative configurations were elucidated by comprehensive spectroscopic methods including NOESY spectra. The absolute configuration of 1 was established by a dimolybdenum tetraacetate [Mo 2 (AcO) 4 ] induced circular dichroism (ICD) procedure and the modified Mosher’s method. Compounds 1 – 12 represent the first series of 9,10-secosteroids characterized with a hydroxy group at C-8, which are 8-OH derivatives of astrogorgiadiols/calicoferols. Compound 4 exhibited cytotoxicity against the cervical carcinoma cell line (CaSki) with an IC 50 value of 2.4 μM, and 6 showed toxicity toward brine shrimp Artemia salina with an LC 50 value of 2.0 μM. [ABSTRACT FROM AUTHOR]

Covering 1972 to 2021 Malaria remains a significant public health problem in some regions of the world. The great efforts to control malaria have been severely compromised due to the widespread resistance of Plasmodium falciparum to nearly all frontline drugs. Pursuit of novel molecules from the sea will potentially result in new interventions against malaria, which are urgently needed to combat the increase of resistance. Focusing on the strategy of the "Blue Drug Bank", the molecules highlighted here can serve as an inspiration for future medicinal chemistry campaigns. This review covers the developments in the field of antimalarial marine lead compounds reported between 1972 and July 2021, and offers a comprehensive overview on their progresses and potentials. We selected 60 representative potential candidate molecules from 361 marine natural products, and highlighted their structure–activity relationships, molecular mechanisms of targets, and drug-like properties in order to assess their full potential to be developed. We summarized 107 clinically proven or potential antimalarial targets and their subcellular locations in the relevant target proteins, which linked the molecules to the target proteins at the subcellular level. Hence, it could be expected that natural products targeting different mechanisms may prove to be an effective strategy in antimalarial drug research and development in the future. [ABSTRACT FROM AUTHOR]

The strong antibacterial, antiviral and anticancer activities demonstrated by quinolones make them promising lead structures and important synthetic targets for drug discovery. Here, we report, to the best of our knowledge, the first scalable total synthesis of antiviral (+)-aniduquinolone A, possessing a 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one skeleton. This synthetic strategy explores E-stereoselective Horner–Wadsworth–Emmons (HWE) olefination as the key step to assemble isopropenyl substituted tetrahydrofuran onto the 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one core, which is built by highly diastereoselective intramolecular aldol reaction. Moreover, two sets of stereoisomers of aniduquinolone A with substantially overlapping NMR data were synthesized completely and assigned unambiguously by comprehensive analysis of both their spectroscopic and X-ray diffraction data. Unexpectedly, aflaquinolones A, C, and D that feature different 2,4-dimethyl cyclohexanone moieties were transformed successfully from (+)-aniduquinolone A by treating with TFA. The methodology delineated herein can be applied broadly to the synthesis of natural alkaloids containing the core structure of 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one. Quinolones can possess desirable antibacterial, antiviral and anticancer properties, rending them important synthetic targets for drug discovery purposes. Here, the gram-scale total synthesis of antiviral (+)-aniduquinolone A, possessing a 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one skeleton, is reported, as well as its acid-catalyzed rearrangement to aflaquinolones A, C, and D. [ABSTRACT FROM AUTHOR]

Abstract: Chemical investigation on soft coral Sarcophyton infundibuliforme collected from the South China Sea led to the isolation and identification of 14 secondary metabolites, including ten cembrene diterpenoids (1–10), one α-tocopheryl quinone derivative (11), one prostaglandin (12), one lipid (13) and one carotinoid (14). Their structures were determined by extensive analysis of their spectroscopic data. All of these metabolites were isolated from this species for the first time. Diterpenoids 1, 2, 7 and 10 showed potent antifouling activity against the larval settlement of barnacle Balanus amphitrite. [Copyright &y& Elsevier]

A new diimide derivative, named ( - )-byssochlamic acid bisdiimide (1), was isolated from the mixed broth of two mangrove fungi (strain no. K38 and E33) from the South China sea coast. The structure of 1 was determined by comprehensive spectroscopic methods, including 1D and 2D NMR (COSY, HMQC, and HMBC) and semi-synthesis. Primary bioassays showed that 1 had weak cytotoxic activity against Hep-2 and HepG2 cells. [ABSTRACT FROM AUTHOR]

Two new metabolites, sarcophytonone (1) and sarcophytonamine (2), have been isolated from the Hainan soft coral Sarcophyton crassocaule. Their structures were elucidated on the basis of a detailed analysis of spectroscopic data, and by comparison of their NMR spectral data with those of the related model compounds. [ABSTRACT FROM AUTHOR]

The adhesion of diatoms to a substrate occurs through the secretion of extracellular polymeric substances (EPS), which is conducive to the growth of other fouling organisms, including barnacles and oysters attached to the diatom surface [[9]]. Furthermore, B 11 b , B 13 b , and B 14 b also displayed broad antidiatom activities against I C. socialis i , I N. leavissima i , and I N. parva i , which indicated that polyhydroxyl substitution of flavones can increase antidiatom activity (Fig. The organic extracts were subjected to silica gel column chromatography (CC) eluted by a gradient of petroleum ether (PE)-EtOAc to EtOAc, and then MeOH to afford five fractions (Frs. [Extracted from the article]

Abstract Tuberculosis has been one of the greatest global health challenges of all time. Although the current first-line anti-tuberculosis (anti-TB) medicines used in the clinic have reduced mortality, multidrug-resistance and extensively drug-resistance forms of the disease have now spread worldwide and become a global problem. Even so, few new clinically approved drugs have emerged during the past 30 years. Highly biodiverse marine organisms have received considerable attention for drug discovery in the past couple of decades, and emerging TB drug resistance has motivated interest in assessing marine natural products (MNPs) in the treatment of this disease. So far, more than 170 compounds have been isolated from marine organisms with anti-TB properties, ten of which exhibit potent activity and have the potential for further development. This review systematically surveys MNPs with anti-TB activity and illustrates the impact of these compounds on drug discovery research against tuberculosis. Graphical abstract Image 1 Highlights • Tuberculosis is widespread, epidemic, and of high mortality. • More than 170 compounds have been isolated from marine organisms with anti-TB properties. • More than ten compounds exhibit potent activity and have the potential for further development. • Multidisciplinary cooperation may accelerate the development of more effective and selective anti-TB agents. [ABSTRACT FROM AUTHOR]

Integrating molecular networking and 1H NMR techniques successfully enabled the discovery of three new cycloheptapeptides, asperversiamides A–C (1–3). Their complete structures were further confirmed by total synthesis. All three compounds exhibited potent inhibitory activity against Mycobacterium marinum. [ABSTRACT FROM AUTHOR]

Benzomalvins B, C, and E (1, 2, and 3) were simultaneously obtained from the marine fungus Aspergillus sp. isolated from the soft coral Sinularia sp., collected from South China Sea. Their structures were elucidated on the basis of NMR spectroscopic data and by comprehensive comparison with those previously reported in the literature. The stability of the double bond of E-benzomalvin B (1) under different light conditions was investigated, and 1 was transformed to Z-benzomalvin B (1′) with UV 365 nm irradiation. In particular, the incorrect 1H NMR data of 1′ in the literature was reassigned for the first time. Moreover, the absolute configuration of benzomalvin C (2) was also reported for the first time by X-ray single crystal diffraction. [ABSTRACT FROM AUTHOR]

Among the large series of marine natural products (MNPs), sulfur-containing MNPs have emerged as potential therapeutic agents for the treatment of a range of diseases. Herein, we reviewed 95 new sulfur-containing MNPs isolated during the period between 2021 and March 2023. In addition, we discuss that the widely used strategies and the emerging technologies including natural product-based antibody drug conjugates (ADCs), small-molecule-based proteolysis targeting chimeras (PROTACs), nanotechnology-based drug carriers, artificial intelligence (AI)-driven drug discovery have been used for improving the efficiency and success rate of NP-based drug development. We also provide perspectives regarding the challenges and opportunities in sulfur-containing MNPs based drug discovery and development and future research directions. [ABSTRACT FROM AUTHOR]

Terphenyllin ( 1 ), a naturally abundant p -terphenyl metabolite, was isolated from the coral derived fungus Aspergillus candidus together with four natural analogues 2 – 5 . To evaluate their potency and selectivity, a series of new derivatives of 1 were designed and semisynthesized. They were evaluated for their α -glucosidase inhibitory, cytotoxic, and antibacterial activities. Compounds 1 , 3 , 4 , 7 , 8 , 10 , 11 , 14 , 15 , 21 , 23 , 24 , 29 , 39 , and 40 showed significant α -glucosidase inhibitory activity with IC 50 values of 4.79–15 μM, which were stronger than that of the positive controls, 1-deoxynojirimycin (IC 50  = 192.0 μM) and acarbose (IC 50  = 707.9 μM). Compounds 7 and 10 have relatively higher therapeutic indices (CC 50 /IC 50  = 17 and 10, respectively), representing potential promising leads. The enzyme kinetic studies of compounds 1 and 24 showed a non-competitive inhibition on α -glucosidase with Ki values of 1.50 and 3.45 μM, respectively. Additionally, compounds 14 , 21 , 26 , 29 , 32 , 35 , and 37 were found to exhibit strong cytotoxicity against three tumor cell lines A549 (lung adenocarcinoma epithelial), HeLa (cervical carcinoma), and HepG2 (hepatocellular liver carcinoma) with IC 50 values ranging from 0.15 to 5.26 μM. Further study indicated that 32 could induce S-phase arrest in the cell cycle progression. [ABSTRACT FROM AUTHOR]

Five acylation derivatives ( 1a- 1e) were prepared by acylation of cytochalasin B ( 1), which was isolated from the marine-derived fungus Curvularia lunata. Compound 1 and its acylation derivatives 1a- 1e were evaluated for their antiviral and cytotoxic activities in vitro. In particular, compound 1e exhibited potent antiviral activity against HSV and EV71 with IC values of 29.5 and 21.4 μM, respectively, which were 4-fold and 11-fold stronger than that of the positive control, ribavirin. [ABSTRACT FROM AUTHOR]

The first total synthesis of aflaquinolone I (1), which represents the first example of natural occurring 3,4-dioxygenated 4-aryl-quinolin-2(1 H)-one alkaloid with 3 R , 4 R configurations, was achieved in 9 and 4 steps by two parallel strategies, respectively. The key steps of the first approach included a base-catalyzed coupling reaction to forge α -hydroxyanilide and a diastereoselective aldol cyclization to construct the 3,4-dioxygenated-4-aryl-quinolin-2(1 H)-one core. The second approach included a regioselective insertion of aryne into unsymmetric imide to build the N -glycolated 2-amino-benzophenone as a key step. In addition, the dehydrated product of aflaquinolone I, viridicatol (2), was successfully synthesized. We also achieved the chiral resolution of (±)-aflaquinolone I (1) and (±)- 20 , using chiral chromatography, and determined the absolute configuration of the enantiomers by electronic circular dichroism (ECD). The absolute configuration of aflaquinolone I was further confirmed. Interestingly, we found that the ECD spectra of aflaquinolone I and its related analogues were affected by the substituted groups on C-4 phenyl group and C-3 hydroxy group. [Display omitted] [ABSTRACT FROM AUTHOR]

Inflammation is connected with a variety of diseases and there is still a need to develop more effective and safer anti-inflammatory drugs. Herein, we synthesized, resolved, and characterized eight enantiopure isomers of yaequinolone J1 (1), yaequinolone J2 (2), 4′-desmethoxyyaequinolone J1 (3), and 4′-desmethoxyyaequinolone J2 (4). The key synthetic steps were extended and 34 racemic analogues modified at the 4-aryl, the N-position, and the pyran ring were designed and synthesized. All the synthesized compounds were evaluated for their anti-inflammatory activities in RAW 264.7 cells of which 13 compounds showed significant inhibition of nitric oxide (NO) production at a concentration of 0.1 μM, which was more potent than that of indomethacin. Furthermore, compounds (−)- 3 , (−)- 4 , 5h, and 6g reduced the production of IL-6 in LPS-stimulated RAW 264.7 cells at a concentration of 50 n M. A preliminary SAR indicated that 3′-Br (5h) , 4′-NO 2 (6g) on 4-phenyl and 3-bromobenzyl (7f) on the N-position were the most effective substituents. This is the first report of the anti-inflammatory yaequinolone alkaloids and the present study provided evidence for exploiting this series of highly efficacious derivatives for new anti-inflammatory agents. [Display omitted] • Yaequinolone fused with an isoprenyl pyran ring reported as a novel chemotype for development of inflammatory inhibitors. • SynThesized eight chiral non-racemic yaequinolones and 34 racemic yaequinolone analogues to establish valuable SARs. • A total of 13 chiral, non-racemic and racemic compounds showed inhibition of NO production at a concentration of 0.1 μM. • Four compounds reduced the production of IL-6 at a concentration of 50 n M. [ABSTRACT FROM AUTHOR]

One new griseofulvin derivative, (+)-5-chlorogriseofulvin ( 1), together with two known analogues, griseofulvin ( 2) and dechlorogriseofulvin ( 3), was isolated from the marine-derived fungus Arthrinium sp. collected from the South China Sea. The structure of the new compound was elucidated on the basis of NMR spectroscopic data and on the basis of the CD experiments compared with those of 2 and 3. Compound 1 exhibited moderate lethality against the brine shrimp Artemia salina with an LC value of 25 μg/mL. All the compounds showed weak antibacterial activity against Dysentery bacillus and Micrococcus luteus with an MIC value of 100 μM. [ABSTRACT FROM AUTHOR]

Marine organism-derived secondary metabolites are promising potential sources for discovering environmentally safe antifouling agents. In present study, 55 marine secondary metabolites and their synthesized derivatives were tested and evaluated for their antifouling activities and security. These compounds include 44 natural products isolated from marine invertebrates and their symbiotic microorganisms collected from the South China Sea and 11 structural modified products derived from the isolated compounds. The natural secondary metabolites, covering phenyl ether derivatives, terpenoids, 9, 11-secosteroids, anthraquinones, alkaloids, nucleoside derivatives and peptides, were isolated from two corals, one sponge and five symbiotic fungi. All of the isolated and synthesized compounds were tested for their antifouling activities against the cyprids of barnacle Balanus ( Amphibalanus) amphitrite Darwin. Noticeably, five phenyl ether derivatives ( 9, 11, 13- 15) exhibited potent anti-larval settlement activity with the EC values lower than 3.05 μM and the LC/EC ratios higher than 15. The study of structure-activity relationship (SAR) revealed that the introduction of acetoxy groups and bromine atoms to phenyl ether derivatives could significantly improve their antifouling activities. This is the first report on the SAR of phenyl ether derivatives on antifouling activity against barnacle B. amphitrite. The polybrominated diphenyl ether derivative, 2, 4, 6, 2′, 4′, 6′-hexabromo-diorcinol ( 13), which displayed excellent antifouling activity, was considered as a promising candidate of environmentally friendly antifouling agents. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and ranks third in mortality rate worldwide. Brefeldin A (BFA, 1), a natural Arf1 inhibitor, qualifies extremely superior antitumor activity against HCC while its low aqueous solubility, poor bioavailability, and high toxicity have greatly hindered its translation to the clinic. Herein, a series of BFA-cinnamic acid ester derivatives was rationally designed and synthesized via introducing active cinnamic acid and its analogues into the structure of 1. Their in vitro cytotoxic activities on five cancer cell lines, including HepG2, BEL-7402, HeLa, Eca-109 and PANC-1, were evaluated using MTT assay. As expected, favorable cytotoxic activity was observed on majority of the mono-substituted derivatives. Especially, the most potent brefeldin A 4- O -(4)-dimethylaminocinnamate (CHNQD-01269, 33) with improved aqueous solubility, demonstrated the strong cytotoxic activity against HepG2 and BEL-7402 cell lines with IC 50 values of 0.29 and 0.84 μ M, respectively. More importantly, 33 performed low toxicity on normal liver cell line L-02 with the selectivity index (SI) of 9.69, which was more than 17-fold higher than that of 1. Results from mechanistic studies represented that 33 blocked the cell cycle in the G1 phase, and induced apoptosis via elevating reactive oxygen species (ROS) production and increasing expression of apoptosis-related proteins of HepG2 cells. Docking experiment also suggested 33 a promising Arf1 inhibitor, which was confirmed by the cellular thermal shift assay that 33 displayed a significant effect on the stability of Arf1 protein. Furthermore, 33 possessed high safety profile (MTD >100 mg/kg, ip) and favorable pharmacokinetic properties. Notably, the superior antiproliferative activity was verified in HepG2 tumor-bearing xenograft model in which 33 markedly suppressed the tumor growth (TGI = 46.17%) in nude mice at a dose of 10 mg/kg once a day for 16 d. The present study provided evidence of exploiting this series of highly efficacious derivatives, especially 33 , for the treatment of HCC. [Display omitted] • New brefeldin A-cinnamic acid ester derivatives were semi-synthesized and evaluated for their cytotoxic activities. • Compound 33 qualified improved aqueous solubility, and higher selectivity index between normal and HCC cell lines. • Compound 33 blocked the cell cycle in the G1 phase, and induced apoptosis via elevating ROS production of HCC cells. • Compound 33 markedly suppressed the tumor growth (TGI = 46.17%) in HepG2 tumor-bearing mice, with low toxicity. [ABSTRACT FROM AUTHOR]

A green and efficient dehydrative SN1-type reaction of indolyl alcohols with diverse nucleophiles was developed using water as the solvent, affording versatile 3-indolyl derivatives in high yields. The advantages of being catalyst-free, environmentally benign, and having a wide substrate scope and easy workup make it a promising method for preparation of indolyl compounds. [ABSTRACT FROM AUTHOR]

This paper describes an efficient SN1-type reaction of 3-indolylmethanols with miscellaneous nucleophiles, featuring a catalyst-free procedure, low cost, wide substrate scope and mild reaction conditions. This approach provides green and efficient methods for the synthesis of diverse 3-substituted indolyl derivatives as well as unsymmetrical bisindolylmethanes and triarylmethanes. [ABSTRACT FROM AUTHOR]

Reinvestigation of the secondary metabolites of the soft coral-derived fungus Pestalotiopsis sp. (ZJ-2009-7-6), cultured in a bromine-modified medium, led to the isolation of three new rhamnosylated phenol derivatives, pestarhamnoses A-C ( 1 - 3 ), together with the former metabolites, (± )-pestalachlorides C and D ( 4 and 5 ). Their structures were elucidated through extensive 1D and 2D NMR spectroscopy and mass spectrometry. The relative configurations of the rhamnosyl moieties were determined as α -rhamnoses by their anomeric J coupling constants. The absolute configurations of 1 - 3 were determined as L-rhamnose residues by HPLC analysis of their thiocarbamoyl-thiazolidine derivatives and that of authentic L-rhamnose. This is the first report of phenol glycosides with α -L-rhamnose in nature. [ABSTRACT FROM AUTHOR]

The isolation and structure elucidation of carteriofenones A - K is reported. [ABSTRACT FROM AUTHOR]

Three new diphenyl ether derivatives, talaromycins A-C, are isolated together with six known analogues and evaluated for their cytotoxic and antifouling activities. [ABSTRACT FROM AUTHOR]

The product template (PT) domains, specifically in fungal non-reducing polyketide synthases (NR-PKSs), mediate the regioselective cyclization of polyketides dominating the final structures. However, up to date, the systematic knowledge about PT domains has been insufficient. In present study, the relationships between sequences, structures and functions of the PT domains were analyzed with 661 NR-PKS sequences. Based on the phylogenetic analysis, the PT domains were classified into prominent eight groups (I-VIII) corresponding with the representative compounds and cyclization regioselectivity (C2-C7, C4-C9, and C6-C11). Most of the cavity lining residue (CLR) sites in all groups were common, while the regional CLR site mutations resulted in the appearance of finger-like regions with different orientation. The cavity volumes and shapes, even the catalytic dyad positions of PT domains in different groups were corresponding with characteristic cyclization regioselectivity and compound sizes. The conservative residues in PT sequences were responsible for the cyclization functions and the evolution of the key residues resulted in the differentiations of cyclization functions. The above findings may help to better understand the cyclization mechanisms of PT domains and even predict the structural types of the aromatic polyketide products. [ABSTRACT FROM AUTHOR]

The article presents a study which focuses on the chemical investigations of secondary metabolites of zoanthid-derived fungus Trichoderma collected from South China Sea. The fungal strain of the Trichoderma was separated from the fresh tissue acquired from the inner part of zoanthid. The study used silica gel column chromatography (CC) with stepwise gradient of petroleum ether.

Hepatocellular carcinoma is one of the most common primary hepatic malignancy. Herein, a series of semisynthesized derivatives (2 – 30) of the natural product (+)-sclerotiorin (1) was prepared and evaluated the cytotoxic activities against six cancer cell lines. Among them, 3 and 5 were the most effective compounds against human hepatocellular carcinoma Bel-7402 cell line with IC 50 values of 1.45 and 1.15 μ M, respectively. Molecular mechanism study showed that 5 disrupted the mitochondrial membrane potential and induced apoptosis in a caspase-dependent manner. In addition, 5 affected AKT and ERK signaling pathways and induced AKT and ERK proteins degradation through ubiquitin-proteasome system. Furthermore, 5 displayed significant in vivo anticancer effects in the xenograft models with decreasing the tumor mass by 52.5%. The safety evaluation was confirmed by acute toxicity subchronic toxicity tests, paraffin sections of mice organ and blood routine examination. Taken together, 5 can be developed as a potential therapeutic agent for hepatocellular carcinoma. [Display omitted] • New (+)-sclerotiorin derivatives were semisynthesized and evaluated cytotoxic activities against six cancer cell lines. • Compound 5 induced AKT and ERK proteins degradation through ubiquitin-proteasome system. • Compound 5 decreased 52.5% of tumor weight in Bel-7402 xenograft tumor models without toxicity. [ABSTRACT FROM AUTHOR]

The article focuses on the chemical constituents of red algae Chondrophycus papillosus (C. papillosus) and their cytotoxic activity. It states that various compounds were isolated and identified from C. papillosus including aristolane sesquiterpenes, linear diterpene, and polybrominated indoles. Moreover,the metabolites such as aristolen-9β-ol, Tetrabomo-1-methyl-1H-indole, and Tetrabromoindole showed cytotoxity against tumor cell lines like chronic myelogenous leukemia cells (K562).