Synthesis,Characterization, and Anti‐Amoebic Activity of N‐(Pyrimidin‐2‐yl)benzenesulfonamide Derivatives

A new series of N‐(pyrimidin‐2‐yl)benzenesulfonamide derivatives, 3a – 3i and 4a – 4i , was synthesized from pyrimidin‐2‐amines, 2a – 2i , with the aim to explore their effects on in vitro growth of Entamoeba histolytica. The chemical structures of the compounds were elucidated by elemental analysis, FT‐IR, ¹H‐ and ¹³C‐NMR, and ESI mass‐spectral data. In vitro anti‐amoebic activity was evaluated against HM1 : IMSS strain of Entamoeba histolytica. The IC₅₀ values were calculated by using the double dilution method. The results were compared with the IC₅₀ value of the standard drug ‘metronidazole’. The selected compounds were tested for their cytotoxic activities by cell‐viability assay using H9C2 cardiac myoblasts cell line, and the results indicated that all the compounds displayed remarkable >80% viabilities to a concentration of 100 μg/ml.     

Synthesis and Characterization of Novel Thiazolo[3,2‐a]pyrimidine Derivatives and Evaluation of Antioxidant and Cytotoxic Activities

A series of novel thiazolo[3,2‐a]pyrimidines were synthesized and characterized by FT‐IR, ¹H, ¹³C‐NMR and mass techniques. Their antioxidant activities were investigated by 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical scavenging assay and the results showed that all the synthesized compounds exhibit good antioxidant activity. In addition, it was found that any substituent on the aromatic ring of the products plays an important role in their antioxidant activity. In vitro cytotoxicity of compounds 4a – 4j was investigated using MTT cell viability assay. Among these compounds, 6‐ethyl 2,3‐dimethyl 5‐(4‐chlorophenyl)‐7‐methyl‐2,3‐dihydro‐5H‐[1,3]thiazolo[3,2‐a]pyrimidine‐2,3,6‐tricarboxylate ( 4e ) bearing a chlorine substituent displayed the highest cytotoxic effect (IC₅₀=6.26±0.6 μm ) in comparison with doxorubicin (IC₅₀=0.68±0.1 μm ) as a standard after 72 h. Therefore, it is assumed that these compounds could be used as effective antioxidant and cytotoxic agents.     

Three New Phenylpropanoids from the Roots of Piper taiwanense and Their Inhibitory Activities on Platelet Aggregation and Mycobacterium tuberculosis

Bioassay‐guided fractionation of the active AcOEt‐soluble fraction from the roots of Piper taiwanense has led to the isolation of two new phenylpropanoids, taiwanensols A and B ( 1 and 2 , resp.), a new natural product, taiwanensol C ( 3 ), and 3‐acetoxy‐4‐hydroxy‐1‐allylbenzene ( 4 ). The compounds were obtained as two isomer mixtures ( 1 / 2 and 3 / 4 , resp.). Their structures were elucidated by spectroscopic analyses, including 1D‐ and 2D‐NMR spectroscopy and mass spectrometry, and by the comparison of their NMR data with those of related compounds. Compounds 1 – 4 were evaluated for their antiplatelet and antitubercular activities. The mixtures 1 / 2 and 3 / 4 showed potent inhibitory activities against platelet aggregation induced by collagen, with IC₅₀ values of 35.2 and 8.8 μM , respectively. In addition, 1 / 2 and 3 / 4 showed antitubercular activities against Mycobacterium tuberculosis H37Rv, with MIC values of 30.0 and 48.0 μg/ml, respectively.     

Bioactive Steroid Derivatives and Butyrolactone Derivatives from a Gorgonian‐Derived Aspergillus sp. Fungus

Six steroid derivatives, 1 – 6 , and five butyrolactone derivatives, 7 – 11 , were isolated from the fermentation broth of a gorgonian‐derived Aspergillus sp. fungus. Their structures were elucidated on the basis of NMR and MS spectral data. Compound 1 is a new, highly conjugated steroid. The NMR and MS data of 7 and 8 are reported for the first time, as their structures were listed in SciFinder Scholar with no associated reference. Compounds 1, 4, 5 , and 8 – 11 inhibited the larval settlement of barnacle Balanus amphitrite with EC₅₀ values ranging from 0.63 to 18.4 μg ml^?1. Butyrolactone derivatives 7 and 8 showed pronounced antibacterial activities against Staphylococcus aureus with the same MIC values as the positive control ciprofloxacin (MIC 1.56 μM for all three compounds).     

Chemical Constituents of the Seed Cake of Camellia oleifera and Their Antioxidant and Antimelanogenic Activities

There is a growing interest in the exploitation of agricultural byproducts. This study explored the potential beneficial health effects from the main biowaste, tea seed pomace of Camellia oleifera Abel (Theaceae), produced when tea seed is processed. Eighteen compounds were isolated from the 70% EtOH extract of the seed cake of C. oleifera. Their structures were determined by ESI‐MS, ¹H‐ and ¹³C‐NMR together with literature data. All fractions and compounds were evaluated for the antioxidant and melanogenesis inhibitory activities. As the result, AcOEt fraction has the best in vitro antioxidant and antimelanogenesis activities, compounds 7 – 12 and 15 showed remarkable antioxidant activity, compounds 4 , 6 , 8 , and 15 – 17 exhibited superior inhibitory activities against melanogenesis. Furthermore, tyrosinase inhibitory activity assay suggested that compound 8 could suppress melanogenesis by inhibiting the expression of tyrosinase.     

Bioactive Diphenyl Ether Derivatives from a Gorgonian‐Derived Fungus Talaromyces sp.

Three new diphenyl ether derivatives, talaromycins A–C ( 1 – 3 , resp.), together with six known analogs, 4 – 9 , were isolated from a gorgonian‐derived fungus, Talaromyces sp. The structures of the new compounds were determined by analysis of extensive NMR spectroscopic data. All of the isolated metabolites, 1 – 9 , were evaluated for their cytotoxic and antifouling activities. Compound 4 exhibited pronounced cytotoxicity against the tested human cell lines with the IC₅₀ values ranging from 4.3 to 9.8 μM . Compounds 3, 5, 8 , and 9 showed potent antifouling activities against the larval settlement of the barnacle Balanus amphitrite with the EC₅₀ values ranging from 2.2 to 4.8 μg/ml.     

Bioactive Neolignans and Other Compounds from Magnolia grandiflora L.: Isolation and Antiplasmodial Activity

Bioassay‐guided fractionation of a methanol extract of Magnolia grandiflora against Plasmodium falciparum yielded two new ( 1 and 2 ) and six known ( 3 – 8 ) bioactive compounds. The structures of the new compounds were assigned by mass spectrometric and 1D‐ and 2D‐NMR data. Known compounds were identified by comparison of ¹H‐NMR and MS data with literature data. The two known neolignans 3 and 4 showed moderate antiplasmodial activity with the IC₅₀ values of 2.8 ± 0.1 and 3.4 ± 0.1 μm , respectively. Weak antiplasmodial activity was recorded for compounds 1 , 2 , 5 , 6 , 7 , and 8 , with the IC₅₀ values of 38 ± 2, 23 ± 2, 16.5 ± 0.2, 86 ± 1, 44 ± 4, and 114 ± 9 μm , respectively.     

Three new cytochalasins from the marine-derived fungus Spicaria elegans KLA03 by supplementing the cultures with L- and D-tryptophan

Three new cytochalasins Z₂₁–Z₂₃ ( 1 – 3 , resp.), together with five analogs, 4 – 8 , were isolated from Spicaria elegans KLA03 by the OSMAC (one strain‐many compounds) approach with adding L ‐ and D ‐tryptophan during its cultivation. The structures of new cytochalasins were elucidated on the basis of comprehensive 1D‐ and 2D‐NMR and HR‐ESI‐MS analyses. Cytochalasins Z₂₁ and Z₂₂ ( 1 and 2 , resp.), and compound 5 showed cytotoxic activities against A‐549 cell lines with IC₅₀ values of 8.2, 20.0, and 3.1 μM , respectively.     

Bifunctional Platinum(II) Complexes with Bisphosphonates Substituted Diamine Derivatives: Synthesis and In vitro Cytotoxicity

A series of N,N′‐dibisphosphonate‐containing 1,3‐propanediamine derivatives ( L1 – L6 ) and their corresponding dichloridoplatinum(II) complexes ( 1 – 6 ) have been synthesized and characterized by elemental analysis, ¹H‐NMR, ¹³C‐NMR, ³¹P‐NMR and HR‐MS spectra. The in vitro antitumor activities of compounds L1 – L6 and 1 – 6 were tested by WST‐8 assay with Cell Counting Kit‐8, indicating that platinum‐based complexes 1 – 6 showed higher cytotoxicity than corresponding ligands L1 – L6 against A549 and MG‐63, especially complex 2 which displayed comparable cytotoxicity to those of cisplatin and zoledronate after 48 h incubation. In addition, complexes 1 – 6 were more active in vitro on osteosarcoma cell line MG‐63 than normal osteoblast cell line hFOB 1.19. The structure‐activity relationship has been summarized based on the in vitro cytotoxicity of three series of platinum complexes from this and our previous studies. The in vitro bone affinity of platinum complexes was also tested by hydroxyapatite (HAP) chromatography in terms of capacity factor K′. Besides, in this paper, representative complex 2 , which has been proved to be a promising antitumor agent with high cytotoxicity and bone HAP binding property, was investigated for its mechanism of action producing cell death against MG‐63.     

Two new resveratrol tetramers isolated from Cayratia japonica (Thunb.) Gagn. with strong inhibitory activity on fatty acid synthase and antioxidant activity

Two new resveratrol tetramers, cajyphenol A ( 1 ) and cajyphenol B ( 2 ), together with two known resveratrol dimers, quadrangularin A ( 3 ) and pallidol ( 4 ), and resveratrol ( 5 ) were isolated from the stems of Cayratia japonica (Thunb. ) Gagn. Their structures were established by means of NMR (¹H,¹H‐COSY, ¹H,¹³C‐HSQC, HMBC, and NOESY) and ESI‐MS analyses. Compounds 1 – 5 showed fast‐binding inhibitory activities on fatty acid synthase with the IC₅₀ values of 1.63±0.02, 1.49±0.03, 7.50±0.01, 11.1±0.01, and 10.2±0.01 μM , respectively. Compounds 1 – 5 also exhibited antioxidant activities in the ORAC assay.     

An Unusual Tetrahydrofuran Lignan from the Roots of Zanthoxylum planispinum and the Potential Anti‐inflammatory Effects

An unusual tetrahydrofuran lignin, zanthplanispine ( 1 ), together with 14 known lignans ( 2 – 15 ) were isolated from the AcOEt‐soluble fraction from the MeOH extract of Z. planispinum roots. The structures of 1 was elucidated on the basis of 1D‐ and 2D‐NMR experiments as well as HR‐ESI‐MS analysis. The known compounds were identified by the comparison of their NMR data with previously reported in the literatures. Bioassay showed that compounds 1 – 4 could inhibit nitric oxide (NO) production in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. In particular, compound 1 showed significant inhibitory activity with an IC₅₀ value of 36.8 μm .     

A Novel Sulfated Holostane Glycoside from Sea Cucumber Holothuria leucospilota

A new sulfated holostane glycoside, leucospilotaside B ( 1 ), together with the two related structurally known compounds holothurin B₂ ( 2 ) and holothurin B ( 3 ), was isolated from sea cucumber Holothuria leucospilota collected from the South China Sea. The structure of 1 was elucidated by spectral analysis (¹H‐, ¹³C‐, and 2D‐NMR, ESI‐MS, and HR‐ESI‐MS) and chemical methods. The compounds 1 – 3 possess the same disaccharide moiety, but were different in the side chains of the triterpene aglycone. Compound 1 showed significant cytotoxicities against four human tumor cell lines, HL‐60, MOLT‐4, A‐549, and BEL‐7402.     

A New Alkaloid from the Aerial Parts of Bupleurum chinense DC.

A new isoalloxazine alkaloid, named bupleurine A ( 1 ), along with five known compounds ( 2 – 6 ), were isolated from the aerial parts of Bupleurum chinense DC. The structure elucidation of the new alkaloid ( 1 ) was employed by combining NMR and HR‐MS data with comparison of reference in the literature. Five known compounds ( 2 – 6 ) were isolated from Bupleurum genus for the first time. Additionally, their antiproliferative activities on HeLa cells were evaluated by MTT assay and IC₅₀ of compounds 1 and 4 – 6 were below 10 μm after treatment for 24 h.     

Cytotoxic Tetraprenylated Alkaloids from the South China Sea Gorgonian Euplexaura robusta

Nine achiral tetraprenylated alkaloids, including three new compounds, named malonganenones I–K ( 1 – 3 , resp.), together with six known analogs, 4 – 9 , were isolated from the gorgonian Euplexaura robusta collected from Weizhou Island of Guangxi Province, China. The structures of compounds 1 – 3 were elucidated by extensive spectral analyses, especially of their 1D‐ and 2D‐NMR data. Compounds 1, 4, 6 , and 7 showed moderate cytotoxicities against K562 and HeLa tumor cell lines with IC₅₀ values ranging from 0.35 to 10.82 μM . Compound 6 also showed moderate inhibitory activity against c‐Met kinase at a concentration of 10 μM .     

Albocycline‐type Macrolides with Antibacterial Activities from Streptomyces sp. 4205

The actinomycete genus Streptomyces is characterized by producing bioactive secondary metabolites, including antibiotics. In this study, chemical and biological investigations were carried out on Streptomyces strain 4205 isolated from the paddy soil, leading to the identification and characterization of 10 albocycline‐type macrolides, among which 4 compounds were new, namely albocyclines A–D ( 1 – 4 ). The structures of 1 – 10 were identified according to the 1D‐ and 2D‐NMR spectroscopic data. Furthermore, compounds 1 – 10 were evaluated for antimicrobial activity. Compounds 5 – 7 displayed antimicrobial activities against Candidaalbicans ATCC 90028 with the same MIC value of 10.0 mg/mL and the IC₅₀ values of 1.5, 1.0, and 1.0 mg/mL, respectively. Thus, the research on Streptomyces sp. is of vital significance for developing new antibiotic agents.     

Bioactive metabolites from the sponge Suberea sp

Two new brominated compounds, subereaphenol K ( 2 ) and 2‐(3,5‐dibromo‐1‐ethoxy‐4‐oxocyclohexa‐2,5‐dien‐1‐yl)acetamide ( 3 ), together with subereaphenol B (methyl 2‐(2,4‐dibromo‐3,6‐dihydroxyphenyl)acetate; 1 ) with a revised structure, and five dibromotyrosine‐derived metabolites, 4 – 8 , were isolated from the sponge Suberea sp. and characterized by 1D‐ and 2D‐NMR spectroscopic and HR‐MS spectrometric data. Compounds 1, 2, 6 , and 8 exhibited various weak or moderate bioactivities, including antimicrobial and cytotoxic activities. Furthermore, compounds 1 and 2 inhibited human recombinant phosphodiesterase 4 (PDE4) with IC₅₀ values of 2 μM , whereas compounds 6 and 8 were less active.     

Structural Characterization and Biological Evaluation of 18‐Nor‐ent‐labdane Diterpenoids from Grazielia gaudichaudeana

The phytochemical investigation of Grazielia gaudichaudeana aerial parts yielded 15 compounds, including diterpenes, triterpenes, sterols and flavonoids. With exception to ent‐kaurenoic acid diterpenes, the compounds isolated are being described for the first time in this species. Some unusual ¹H‐NMR chemical shifts of 18‐nor‐ent‐labdane ( 7 – 9 ) led us carry out a conformational analysis by theoretical calculations in order to support the experimental data. Moreover, due to the limitation of studies focused on pharmacological potential of Grazielia gaudichaudeana, the present study was carried out to investigate the antioxidant, antiproliferative, antiviral, antileishmanial and antimicrobial activities from the extract, fractions and isolated compounds obtained from this species. Ethyl acetate fraction showed significant activity in the antiproliferative assay, with GI₅₀ range of 3.9 to 27.2 μg mL^?1. Dichloromethane fraction, rich in diterpenoids, inhibited all human tumor cell lines tested, and the nor‐labdane 7 showed potent cytotoxic activity against glioma and ovary cancer cell lines.     

Julichrome Monomers from Marine Gastropod Mollusk‐Associated Streptomyces and Stereochemical Revision of Julichromes Q3 ⋅ 5 and Q3 ⋅ 3

Two julichrome monomers, julichromes Q₁₁ ( 1 ) and Q₁₂ ( 2 ), along with five known julichromes (Q₁₀, Q_{3 ? 5}, Q_{3 ? 3}, Q_{6 ? 6}, Q₆, 3 – 7 ) and four known anthraquinones (chrysophanol, 4‐acetylchrysophanol, islandicin, huanglongmycin A, 8 – 11 ), were isolated from the marine gastropod mollusk Batillaria zonalis‐associated Streptomyces sampsonii SCSIO 054. This is the first report of julichromes isolated from a marine source. Extensive dissection of 1D and 2D NMR datasets combined with X‐ray crystallography enabled rigorous elucidation of the previously reported configurations of julichrome Q_{3 ? 5} ( 4 ) and related julichrome Q_{3 ? 3} ( 5 ); both of the configuration at C(9) needs to be revised. In addition, julichrome Q₁₂ ( 2 ) was found to display antibacterial activity against Micrococcus luteus and Bacillus subtilis with MICs of 2.0 and 8.0 μg mL^?1; four compounds ( 1 , 3 , 6 , 7 ) also showed inhibitory activities against an array of methicillin‐resistant Staphylococcus aureus, S. aureus and S. simulans AKA1 with MIC values ranging from 8 to 64 μg mL^?1.     

Synthesis and Antifungal Activities of Trichodermin Derivatives as Fungicides on Rice

Twenty new trichodermin derivatives, 2a – 5 , containing alkoxy, acyloxy, and Br groups in 4‐, 8‐, 9‐, 10‐ and 16‐positions were synthesized and characterized. The antifungal activities of the new compounds against rice false smut (Ustilaginoidea virens), rice sheath blight (Rhizoctonia solani), and rice blast (Magnaporthe grisea) were evaluated. The results of bioassays indicated that the antifungal activities were particularly susceptible to changes at 4‐, 8‐, and 16‐positions, but low to changes at 9‐ and 10‐positions. Most of these target compounds exhibited good antifungal activities at the concentration of 50 mg l^?1. Compound 4 (9‐formyltrichodermin; EC₅₀ 0.80 mg l^?1) with an CHO group at 9‐position displayed nearly the same level of antifungal activity against Ustilaginoidea virens as the commercial fungicide prochloraz (EC₅₀ 0.82 mg l^?1), while compound 3f ((8R)‐8‐{[(E)‐3‐phenylprop‐2‐enoyl]oxy}trichodermin; EC₅₀ 3.58 and 0.74 mg l^?1) with a cinnamyloxy group at C(8) exhibited much higher antifungal activities against Rhizoctonia solani and Magnaporthe grisea than the commercial fungicides prochloraz (EC₅₀ 0.96 mg l^?1) and propiconazole (EC₅₀ 5.92 mg l^?1), respectively. These data reveal that compounds 3f and 4 possess high antifungal activities and may serve as lead compounds for the development of fungicides in the future.