Melanogenesis‐Inhibitory and Cytotoxic Activities of Limonoids,Alkaloids, and Phenolic Compounds from Phellodendron amurense Bark

Four limonoids, 1  –  4 , five alkaloids, 5  –  9 , and four phenolic compounds, 10  –  13 , were isolated from a MeOH extract of the bark of Phellodendron amurense (Rutaceae). Among these, compound 13 was new, and its structure was established as rel‐(1R,2R,3R)‐5‐hydroxy‐3‐(4‐hydroxy‐3‐methoxyphenyl)‐6‐methoxy‐1‐(methoxycarbonylmethyl)indane‐2‐carboxylic acid methyl ester (γ‐di(methyl ferulate)) based on the spectrometric analysis. Upon evaluation of compounds 1  –  13 against the melanogenesis in the B16 melanoma cells induced with α‐melanocyte‐stimulating hormone (α‐MSH), four compounds, limonin ( 1 ), noroxyhydrastinine ( 6 ), haplopine ( 7 ), and 4‐methoxy‐1‐methylquinolin‐2(1H)‐one ( 8 ), exhibited potent melanogenesis‐inhibitory activities with almost no toxicity to the cells. Western blot analysis revealed that compound 6 inhibited melanogenesis, at least in part, by inhibiting the expression of protein levels of tyrosinase, TRP‐1, and TRP‐2 in α‐MSH‐stimulated B16 melanoma cells. In addition, when compounds 1  –  13 were evaluated for their cytotoxic activities against leukemia (HL60), lung (A549), duodenum (AZ521), and breast (SK‐BR‐3) cancer cell lines, five compounds, berberine ( 5 ), 8 , canthin‐6‐one ( 9 ), α‐di‐(methyl ferulate) ( 12 ), and 13 , exhibited cytotoxicities against one or more cancer cell lines with IC₅₀ values in the range of 2.6 – 90.0 μm . In particular, compound 5 exhibited strong cytotoxicity against AZ521 (IC₅₀ 2.6 μm ) which was superior to that of the reference cisplatin (IC₅₀ 9.5 μm ).     

Cytotoxic and Apoptosis‐inducing Activities of Taraxastane‐type Triterpenoid Derivatives in Human Cancer Cell Lines

Twenty‐eight taraxastane‐type triterpenoid derivatives 4  –  31 were prepared from the naturally occurring triterpenoids faradiol ( 1 ) and heliantriol C ( 3 ). The cytotoxic activities of these compounds and arnidiol ( 2 ) were evaluated in leukemia (HL60), lung (A549), duodenal (AZ521), and breast (SK‐BR‐3) cancer cell lines. 21‐Oxoarnidiol ( 18 ) and faradiol 3,16‐di‐O‐l ‐alaninate ( 31 ) exhibited potent cytotoxicity, with 50% inhibitory concentrations of 0.5 – 2.7 μm . In particular, flow cytometric analysis indicated that compound 31 induced typical apoptotic cell death in HL60 cells. These results suggested that taraxastane‐type triterpenoid derivatives might provide useful antitumor agents with apoptosis‐inducing activity.     

Cytotoxic and Apoptosis‐Inducing Activities,and Anti‐Tumor‐Promoting Effects of Cyanogenated and Oxygenated Triterpenes

Two of each semisynthetic lanostane‐ and cycloartane‐type triterpenes with a cyano‐enone functionality, i.e., 13 and 18 , and 23 and 28 , respectively, sixteen of their synthetic intermediates, 9 – 12, 14 – 17, 19 – 22 , and 24 – 27 , along with seven semisynthetic oxygenated triterpene acetates, 29 – 35 , and eight natural hydroxy triterpenes, 1 – 8 , were evaluated for their cytotoxic activities against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK‐BR‐3) cancer cell lines. One natural triterpene, 8 , and ten semisynthetic triterpenes, 9, 13, 15, 18, 23, 25, 28, 29, 32 , and 33 , exhibited potent cytotoxicities against one or more cell lines with IC₅₀ values in the range of 1.4–9.9 μM . Two lanostane‐type triterpenes with a cyano‐enone functionality, 3‐oxolanosta‐1,8,24‐triene‐2‐carbonitrile ( 13 ) and 3‐oxolanosta‐1,8‐diene‐2‐carbonitrile ( 18 ), induced apoptosis in HL60 cells, as observed by membrane phospholipid exposure in flow cytometry. Western blot analysis showed that 13 and 18 significantly reduced procaspases‐3, ‐8, and ‐9, and increased cleaved caspases‐3, ‐8, and ‐9. These findings indicated that compounds 13 and 18 induced apoptosis in HL60 cells via both the mitochondrial and the death receptor‐mediated pathways. In addition, upon evaluation of the inhibitory effects on Epstein? Barr virus early antigen (EBV‐EA) activation induced with 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in Raji cells, seven natural triterpenes, 1 – 6 and 8 , and ten semisynthetic triterpenes, 9, 10, 14, 15, 19, 20, 24, 25, 29 , and 30 , exhibited inhibitory effects which were higher than that of β‐carotene, a vitamin A precursor studied widely in cancer‐chemoprevention animal models.     

Pyranochromones from Dictyoloma vandellianum A. Juss and Their Cytotoxic Evaluation

One new chromone 3,3‐dimethylallylspatheliachromene methyl ether ( 1 ), as well as five known chromones, 6‐(3‐methylbut‐2‐enyl) allopteroxylin methyl ether ( 2 ), 6‐(3‐methylbut‐2‐enyl) allopteroxylin ( 3 ), 3,3‐dimethylallylspatheliachromene ( 4 ), 5‐O‐methylcneorumchromone K ( 5 ) and spatheliabischromene ( 6 ), two alkaloids, 8‐methoxy‐N‐methylflindersine ( 7 ) and 8‐methoxyflindersine ( 8 ), and two limonoids, limonin diosphenol ( 9 ) and rutaevin ( 10 ), were isolated from Dictyoloma vandellianum A. Juss (Rutaceae). Cytotoxic activities towards tumor cell lines B16‐F10, HepG2, K562 and HL60 and non‐tumor cells PBMC were evaluated for compounds 1  –  6 . Compound 1 was the most active showing IC₅₀ values ranging from 6.26 to 14.82 μg/ml in B16‐F10 and K562 cell lines, respectively, and presented IC₅₀ value of 11.65 μg/ml in PBMC cell line.     

Synthesis of Lanostane‐Type Triterpenoid N‐Glycosides and Their Cytotoxicity against Human Cancer Cell Lines

Seventeen lanostane‐type triterpenoid derivatives ( 2 – 18 ), including 11N‐glycosides ( 8 – 18 ), were synthesized from the natural triterpenoid, lanosterol ( 1 ), and were evaluated for their cytotoxicity against the human cancer cell lines, HL‐60, A549, and MKN45, as well as the normal human lung cells, WI‐38. Among them, N‐β‐d ‐2‐acetamido‐2‐deoxyglucoside ( 10 ) showed cytotoxicity against HL‐60, A549, MKN45, and WI‐38 cells (IC₅₀ 0.0078 – 2.8 μm ). However, N‐β‐d ‐galactoside ( 12 ) showed cytotoxicity against HL‐60 and MKN45 cells (IC₅₀ 0.0021 – 4.0 μm ), but not the normal WI‐38 cells. Furthermore, Western blot analysis suggested that 12 induces apoptosis by activation of caspases‐3, 8, and 9. These results will be useful for the synthesis of other tetracyclic triterpenoids or steroid N‐glycosides to increase their cytotoxicity and apoptosis‐inducing activities.     

Cytotoxic and Nitric Oxide Production‐Inhibitory Activities of Limonoids and Other Compounds from the Leaves and Bark of Melia azedarach

Nine limonoids, 1 – 9 , one apocarotenoid, 11 , one alkaloid, 12 , and one steroid, 13 , from the leaf extract; and one triterpenoid, 10 , five steroids, 14 – 18 , and two flavonoids, 19 and 20 , from the bark extract of Melia azedarach L. (Chinaberry tree; Meliaceae) were isolated. Among these compounds, three compounds, 4 – 6 , were new, and their structures were established as 3‐deacetyl‐28‐oxosalannolactone, 3‐deacetyl‐28‐oxosalanninolide, and 3‐deacetyl‐17‐defurano‐17,28‐dioxosalannin, respectively, on the basis of extensive spectroscopic analyses and comparison with literature data. All of the isolated compounds were evaluated for their cytotoxic activities against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK‐BR‐3) cancer cell lines. 3‐Deacetyl‐4′‐demethyl‐28‐oxosalannin ( 3 ) against HL60 and AZ521 cells, and methyl kulonate ( 10 ) against HL60 cells exhibited potent cytotoxicities with IC₅₀ values in the range of 2.8–5.8 μM . In addition, upon evaluation of compounds 1 – 13 against production of nitric oxide (NO) in mouse macrophage RAW 264.7 cells induced by lipopolysaccharide (LPS), seven, i.e., trichilinin B ( 1 ), 4 , ohchinin ( 7 ), 23‐hydroxyohchininolide ( 8 ), 21‐hydroxyisoohchininolide ( 9 ), 10 , and methyl indole 3‐carboxylate ( 12 ), inhibited production of NO with IC₅₀ values in the range of 4.6–87.3 μM with no, or almost no, toxicity to the cells (IC₅₀ 93.2–100 μM ). Western blot analysis revealed that compound 7 reduced the expression levels of the inducible NO synthase (iNOS) and COX‐2 proteins in a concentration‐dependent manner. Furthermore, compounds 5, 6, 13 , and 18 – 20 exhibited potent inhibitory effects (IC₅₀ 299–381 molar ratio/32 pmol TPA) against Epstein? Barr virus early antigen (EBV‐EA) activation induced by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in Raji cell line.     

Melanogenesis‐Inhibitory and Cytotoxic Activities of Diarylheptanoids from Acer nikoense Bark and Their Derivatives

Nine cyclic diarylheptanoids, 1 – 9 , including two new compounds, i.e., 9‐oxoacerogenin A ( 8 ) and 9‐O‐β‐D ‐glucopyranosylacerogenin K ( 9 ), along with three acyclic diarylheptanoids, 10 – 12 , and four phenolic compounds, 13 – 16 , were isolated from a MeOH extract of the bark of Acer nikoense (Aceraceae). Acid hydrolysis of 9 yielded acerogenin K ( 17 ) and D ‐glucose. Two of the cyclic diarylheptanoids, acerogenin A ( 1 ) and (R)‐acerogenin B ( 5 ), were converted to their ether and ester derivatives, 18 – 24 and 27 – 33 , respectively, and to the dehydrated derivatives, 25, 26, 34 , and 35 . Upon evaluation of compounds 1 – 16 and 18 – 35 for their inhibitory activities against melanogenesis in B16 melanoma cells, induced with α‐melanocyte‐stimulating hormone (α‐MSH), eight natural glycosides, i.e., six diarylheptanoid glycosides, 2 – 4, 6, 9 , and 12 , and two phenolic glycosides, 15 and 16 , exhibited inhibitory activities with 24–61% reduction of melanin content at 100 μM concentration with no or almost no toxicity to the cells (88–106% of cell viability at 100 μM ). In addition, when compounds 1 – 16 and 18 – 35 were evaluated for cytotoxic activity against human cancer cell lines, two natural acyclic diarylheptanoids, 10 and 11 , ten ether and ester derivatives, 18 – 22 and 27 – 31 , and two dehydrated derivatives, 34 and 35 , exhibited potent cytotoxicities against HL60 human leukemia cell line (IC₅₀ 8.1–19.3 μM ), and five compounds, 10, 11, 20, 29 , and 30 , against CRL1579 human melanoma cell line (IC₅₀ 10.1–18.4 μM ).     

Synthesis and Anticancer Activity of 3‐(Substituted Aroyl)‐4‐(3,4,5‐trimethoxyphenyl)‐1H‐pyrrole Derivatives

A series of 3‐(substituted aroyl)‐4‐(3,4,5‐trimethoxyphenyl)‐1H‐pyrrole derivatives were synthesized and determined for their anticancer activity against eleven cancer cell lines and two normal tissue cell lines using MTT assay. Among the synthesized compounds, compound 3f was the most potent compound against A375, CT‐26, HeLa, MGC80‐3, NCI‐H460 and SGC‐7901 cells (IC₅₀ = 8.2 – 31.7 μm ); 3g , 3n and 3a were the most potent compounds against CHO (IC₅₀ = 8.2 μm ), HCT‐15 (IC₅₀ = 21 μm ) and MCF‐7 cells (IC₅₀ = 18.7 μm ), respectively. Importantly, all the target compounds showed no cytotoxicity towards the normal tissue cell (IC₅₀ > 100 μm ). Thus, these compounds with the potent anticancer activity and low toxicity have potential for the development of new anticancer chemotherapy agents.     

Synthesis and Biological Evaluation of Matijin‐Su Derivatives as Potential Antihepatitis B Virus and Anticancer Agents

A series of Matijin‐Su (MTS, (2S)‐2‐{[(2S)‐2‐benzamido‐3‐phenylpropanoyl]amino}‐3‐phenylpropyl acetate) derivatives were synthesized and evaluated for their anti‐HBV and cytotoxic activities in vitro. Six compounds ( 4g , 4j , 5c , 5g , 5h and 5i ) showed significant inhibition against HBV DNA replication with the IC₅₀ values in range of 2.18 – 8.55 μm , which were much lower than that of positive control lamivudine (IC₅₀ 82.42 μm ). In particular, compounds 5h (IC₅₀ 2.18 μm ; SI 151.59) and 5j (IC₅₀ 5.65 μm ; SI 51.16) displayed relatively low cytotoxicities, resulting in high SI values. Notably, besides the anti‐HBV DNA replication activity, compound 4j also exhibited more potent in vitro cytotoxic activity than 5‐fluorouracil in two hepatocellular carcinoma cell (HCC) lines (QGY‐7701 and SMMC‐7721), indicating that 4j may be a promising lead for the exploration of drugs with dual therapeutic effects on HBV infection and HBV‐induced HCC.     

Vibsane‐Type Diterpenoids from Viburnum odoratissimum and Their Cytotoxic and HSP90 Inhibitory Activities

Four new vibsane‐type diterpenoids, vibsanol I ( 1 ), 15‐hydroperoxyvibsanol A ( 2 ), 14‐hydroperoxyvibsanol B ( 3 ), 15‐O‐methylvibsanin U ( 4 ), and a new natural product, 5,6‐dihydrovibsanin B ( 5 ), as well as six known analogues, were isolated from the twigs and leaves of Viburnum odoratissimum. Their structures were elucidated by spectroscopic analyses and chemical derivatization method. All compounds showed different levels of cytotoxicity against five cell lines (HL‐60, A‐549, SMMC‐7721, MCF‐7, and SW480). Remarkably, 14,18‐O‐diacetyl‐15‐O‐methylvibsanin U ( 4a ) showed significant cytotoxicity against HL‐60, A‐549, SMMC‐7721, MCF‐7, and SW480, with IC₅₀ values of 0.15 ± 0.01, 0.69 ± 0.01, 0.41 ± 0.02, 0.75 ± 0.03, and 0.48 ± 0.03 μm , respectively. In addition, vibsanin K ( 10 ) was identified as a HSP90 inhibitor with an IC₅₀ value of 19.16 μm .     

Cytotoxic Activities of Amino Acid‐Conjugate Derivatives of Abietane‐Type Diterpenoids against Human Cancer Cell Lines

Nine amino acid conjugate derivatives, each 2 – 10 and 12 – 20 , were prepared from abietic acid ( 1 ) and dehydroabietic acid ( 11 ), respectively, and they were evaluated for their cytotoxicities against four human cancer cell lines, i.e., leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK‐BR‐3). All compounds showed cytotoxicities against HL60 with IC₅₀ values in the range of 2.3–37.3 μM . In addition, most of the derivatives exhibited moderate cytotoxicities against the other cancer cell lines. Among the derivatives, methyl N‐[18‐oxoabieta‐8,11,13‐trien‐18‐yl]‐L ‐tyrosinate ( 19 ) exhibited potent cytotoxic activities against four cancer cell lines with IC₅₀ values of 2.3 (HL60), 7.1 (A549), 3.9 (AZ521), and 8.1 μM (SK‐BR‐3). Furthermore, all derivatives were shown to possess high selective cytotoxic activities for leukemia cells, since they exhibited only weak cytotoxicities against normal lymphocyte cell line RPMI1788.     

Two New Anti‐Proliferative C18‐Norditerpenes from the Roots of Podocarpus macrophyllus

Activity‐guided fractionation strategy was used to investigate chemical constituents from the roots of Podocarpus macrophyllus. Successfully, two new norditerpenes, 2β‐hydroxymakilactone A ( 1 ) and 3β‐hydroxymakilactone A ( 2 ), along with ten known analogues ( 3  –  12 ) were isolated. The structures of 1 and 2 were elucidated by spectroscopic analysis including 1D‐, 2D‐NMR, and HR‐ESI‐MS data. The previously reported structure of 2,3‐dihydro‐2α‐hydroxypodolide was revised as 2,3‐dihydro‐2β‐hydroxypodolide ( 3 ) by spectroscopic analysis, and was further confirmed by X‐ray crystallographic analysis. Cytotoxic activities of all isolated compounds against five human solid tumour cell lines (AGS, HeLa, MDA‐MB‐231, HepG‐2, and PANC‐1) were evaluated. All of them exhibited anti‐proliferative activities (IC₅₀ = 0.3 – 27 μm ), except for 10 . Compounds 1 , 4 , 5 , 6 , and 8 exhibited potent inhibitory activities with IC₅₀ < 1 μm against HeLa and AGS cells.     

Carbonic Anhydrase and Urease Inhibitory Potential of Various Plant Phenolics Using in vitro and in silico Methods

Plant phenolics are known to display many pharmacological activities. In the current study, eight phenolic compounds, e.g., luteolin 5‐O‐β‐glucoside ( 1 ), methyl rosmarinate ( 2 ), apigenin ( 3 ), vicenin 2 ( 4 ), lithospermic acid ( 5 ), soyasaponin II ( 6 ), rubiadin 3‐O‐β‐primeveroside ( 7 ), and 4‐(β‐d ‐glucopyranosyloxy)benzyl 3,4‐dihydroxybenzoate ( 8 ), isolated from various plant species were tested at 0.2 mm against carbonic anhydrase‐II (CA‐II) and urease using microtiter assays. Urease inhibition rate for compounds 1  –  8 ranged between 5.0 – 41.7%, while only compounds 1 , 2 , and 4 showed a considerable inhibition over 50% against CA‐II with the IC₅₀ values of 73.5 ± 1.05, 39.5 ± 1.14, and 104.5 ± 2.50 μm , respectively, where IC₅₀ of the reference (acetazolamide) was 21.0 ± 0.12 μm . In silico experiments were also performed through two docking softwares (Autodock Vina and i‐GEMDOCK) in order to find out interactions between the compounds and CA‐II. Actually, compounds 6 (30.0%) and 7 (42.0%) possessed a better binding capability toward the active site of CA‐II. According to our results obtained in this study, among the phenolic compounds screened, particularly 1 , 2 , and 4 appear to be the promising inhibitors of CA‐II and may be further investigated as possible leads for diuretic, anti‐glaucoma, and antiepileptic agents.     

Four New Tirucallane Triterpenoids from the Fruits of Melia azedarach and Their Cytotoxic Activities

Four new tirucallane triterpenoids, (21S,23R,24R)‐21,23‐epoxy‐21,24‐dihydroxy‐25‐methoxytirucall‐7‐en‐3‐one ( 2 ), (3S,21S,23R,24S)‐21,23‐epoxy‐21,25‐dimethoxytirucall‐7‐ene‐3,24‐diol ( 8 ), (21S,23R,24R)‐21,23‐epoxy‐24‐hydroxy‐21‐methoxytirucalla‐7,25‐dien‐3‐one ( 11 ), and (21S,23R,24R)‐21,23‐epoxy‐21,24‐dihydroxytirucalla‐7,25‐dien‐3‐one ( 12 ), along with 16 known analogues, 1 , 3  –  7 , 9  –  10 , and 13  –  20 , were isolated from the fruits of Melia azedarach. Their structures were elucidated by spectroscopic methods including 1D‐ and 2D‐NMR techniques and mass spectrometry. These compounds were evaluated for their cytotoxicities against HepG2 (liver), SGC7901 (stomach), K562 (leukemia), and HL60 (leukemia) cancer cell lines. Compound 20 exhibited potent cytotoxicity against HepG2 and SGC7901 cancer cells with the IC₅₀ values of 6.9 and 6.9 μm , respectively.     

Cytotoxic and Apoptosis‐Inducing Activities of Steviol and Isosteviol Derivatives against Human Cancer Cell Lines

Seventeen steviol derivatives, i.e., 2 – 18 , and 19 isosteviol derivatives, i.e., 19 – 37 , were prepared from a diterpenoid glycoside, stevioside ( 1 ). Upon evaluation of the cytotoxic activities of these compounds against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK‐BR‐3) cancer cell lines, nine steviol derivatives, i.e., 5 – 9 and 11 – 14 , and five isosteviol derivatives, i.e., 28 – 32 , exhibited activities with single‐digit micromolar IC₅₀ values against one or more cell lines. All of these active compounds possess C(19)‐O‐acyl group, and among which, ent‐kaur‐16‐ene‐13,19‐diol 19‐O‐4′,4′,4′‐trifluorocrotonate ( 14 ) exhibited potent cytotoxicities against four cell lines with IC₅₀ values in the range of 1.2–4.1 μM . Compound 14 induced typical apoptotic cell death in HL60 cells upon evaluation of the apoptosis‐inducing activity by flow‐cytometric analysis. These results suggested that acylation of the 19‐OH group of kaurane‐ and beyerane‐type diterpenoids might be useful for enhancement of their cytotoxicities with apoptosis‐inducing activity.     

Cytotoxic and Melanogenesis‐Inhibitory Activities of Limonoids from the Leaves of Azadirachta indica (Neem)

Seventeen limonoids (tetranortriterpenoids), 1 – 17 , including three new compounds, i.e., 17‐defurano‐17‐(2,5‐dihydro‐2‐oxofuran‐3‐yl)‐28‐deoxonimbolide ( 14 ), 17‐defurano‐17‐(2ξ‐2,5‐dihydro‐2‐hydroxy‐5‐oxofuran‐3‐yl)‐28‐deoxonimbolide ( 15 ), and 17‐defurano‐17‐(5ξ‐2,5‐dihydro‐5‐hydroxy‐2‐oxofuran‐3‐yl)‐2′,3′‐dehydrosalannol ( 17 ), were isolated from an EtOH extract of the leaf of neem (Azadirachta indica). The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses and comparison with literature. Upon evaluation of the cytotoxic activities of these compounds against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK‐BR‐3) cancer cell lines, seven compounds, i.e., 1 – 3, 12, 13, 15 , and 16 , exhibited potent cytotoxicities with IC₅₀ values in the range of 0.1–9.9 μM against one or more cell lines. Among these compounds, cytotoxicity of nimonol ( 1 ; IC₅₀ 2.8 μM ) against HL60 cells was demonstrated to be mainly due to the induction of apoptosis by flow cytometry. Western blot analysis suggested that compound 1 induced apoptosis via both the mitochondrial and death receptor‐mediated pathways in HL60 cells. In addition, when compounds 1 – 17 were evaluated for their inhibitory activities against melanogenesis in B16 melanoma cells, induced with α‐melanocyte‐stimulating hormone (α‐MSH), seven compounds, 1, 2, 4 – 6, 15 , and 16 , exhibited inhibitory activities with 31–94% reduction of melanin content at 10 μM concentration with no or low toxicity to the cells (82–112% of cell viability at 10 μM ). All 17 compounds were further evaluated for their inhibitory effects against the Epstein? Barr virus early antigen (EBV‐EA) activation induced by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in Raji cells.     

Phenolic Compounds from Clinopodium chinense (Benth.) O. Kuntze and Their Inhibitory Effects on α‐Glucosidase and Vascular Endothelial Cells Injury

Following an in vitro bioactivity‐guided fractionation procedure, 14 compounds including eight flavonoids and six phenylpropanoids were isolated and identified from the AcOEt fraction of Clinopodium chinense (Benth .) O. Kuntze . All constituents were tested for α‐glucosidase and high glucose‐induced injury in human umbilical vein endothelial cells (HUVECs) inhibitory activities. All constituents exhibited varying degrees α‐glucosidase inhibitory activity and protective activity on HUVECs. Among them, luteolin ( 2 ), eriodictyol ( 5 ), ethyl rosmarinate ( 13 ), and clinopodic acids B ( 14 ) were proved to be potent α‐glucosidase inhibitors with IC₅₀ value ranging from 0.6 to 2.0 μm . Additionally, luteolin ( 2 ), naringenin ( 4 ), eriodictyol ( 5 ), ethyl (2R)‐3‐(3, 4‐dihydroxyphenyl)‐2‐hydroxypropanate ( 9 ), caffeic acid ( 11 ), ethyl rosmarinate ( 13 ), and clinopodic acids B ( 14 ) significantly ameliorate HUVECs injury induced by high glucose with an approximate EC₅₀ value of 3 – 36 μm . These results suggest that the 14 bioactive constituents were responsible for hypoglycemic and protective vascular endothelium effect of C. chinense (Benth .) O. Kuntze and their structure–activity relationship was also analyzed briefly. Eriodictyol, luteolin, ethyl rosmarinate, and clinopodic acids B were the potential lead compounds of antidiabetic drugs.     

Cytotoxic Triterpenoids from the Barks of Betula platyphylla var. japonica

Phytochemical investigation on the barks of Betula platyphylla var. japonica (Betulaceae) was carried out, resulting in the isolation and identification of three new triterpenoids, 27‐O‐cis‐caffeoylcylicodiscic acid ( 1 ), 27‐O‐cis‐feruloylcylicodiscic acid ( 2 ), and 27‐O‐cis‐caffeoylmyricerol ( 3 ), along with six known triterpenoids, obtusilinin ( 4 ), winchic acid ( 5 ), 27‐O‐trans‐caffeoylcylicodiscic acid ( 6 ), uncarinic acid E ( 7 ), myriceric acid B ( 8 ), and 3‐O‐trans‐caffeoyloleanolic acid ( 9 ). The structures of the new compounds were elucidated by extensive spectroscopic methods, including 1D‐ and 2D‐NMR, and HR‐ESI‐MS. All of the isolated compounds were evaluated for cytotoxicity against four human tumor cell lines (A549, SK‐OV‐3, SK‐MEL‐2, and Bt549). Compounds 2 , 6 , 8 , and 9 exhibited potent cytotoxicity against all of the tumor cells tested (IC₅₀ < 10.0 μm ), while compounds 3 , 4 , 5 , and 7 showed moderate cytotoxicity against all of the tumor cells tested (IC₅₀ < 20.0 μm ).     

Total Synthesis and Antibacterial Study of Cyclohexapeptides Desotamide B,Wollamide B and Their Analogs

As natural‐product‐derived antibiotics, desotamides A – D and wollamides exhibit growth inhibitory activity against Gram‐posivite bacteria (IC₅₀ 0.6 – 7 μm ) and are noncytotoxic to mammalian cells (IC₅₀ > 30 μm ). Herein we firstly report the total synthesis of above two cyclohexapeptides as well as a series of structural variants through solid phase peptide synthesis, of which 3 displayed a 2‐fold increase of antibacterial activity when compared with the original peptide 1 . This strategy may offer good improvements for the synthesis of other cyclic peptides.