Calaxanthones A-C,three new xanthones from the roots of Calophyllum calaba and the cytotoxicity

Three new xanthones, named calaxanthones A-C (1–3), along with 17 known xanthones (4–20) were isolated from the roots of Calophyllum calaba. Their structures were determined by spectroscopic analysis. All isolated compounds were evaluated for their cytotoxicity against five cancer cell lines (KB, HeLa S-3, HT-29, MCF-7 and HepG-2). Compound 3 showed potent cytotoxicity against all the five cancer cell lines with IC₅₀ values in the range of 0.82–5.04 μM. Furthermore, compound 6 showed potent cytotoxicity against KB, HeLa S-3 and HepG2 cells with IC₅₀ values of 7.06, 5.27 and 9.64 μM, respectively. Additionally, compound 7 showed potent cytotoxicity against KB cell with an IC₅₀ value of 4.62 μM.     

Chemical characterization of constituents from Polygonatum cyrtonema Hua and their cytotoxic and antioxidant evaluation

Abstract

Twenty-four compounds were isolated from the roots of Polygonatum cyrtonema Hua, including a new octopamine dimer, named trans-bis(N-feruloyl)octopamine (1). The structure was established on the basis of spectroscopic and chemical methods. All the extracts and compounds were evaluated for cytotoxic and antioxidant activities by using MTT and chemiluminescence assay. The extracts showed activity against MCF-7 and HepG-2 cell lines from IC₅₀ 0.30 to 1.01 mg mL^?1. Compound 3 exhibited activity against HepG-2 cell lines with IC₅₀ 8.99?μM. Compound 7 exhibited activity against Hela cell lines with IC₅₀ 2.53?μM and BGC-823 cell lines with IC₅₀ 7.77?μM. Moreover, compound 7 showed antioxidant with IC₅₀ 12?µM compared to the positive control with IC₅₀ 77?µM. Compound 16 exhibited activity against HepG-2 cell lines with IC₅₀ 1.05?μM and MCF-7 cell lines with IC₅₀ 1.89?μM. These results indicated that this plant might be potential in natural medicine and healthy food.     

Chemical constituents,cytotoxic and antioxidant activities of extract from the rhizomes of Osmunda japonica Thunb

Abstract

Thirty-three compounds (1–33) were isolated from the rhizomes of Osmunda japonica. Their structures were elucidated on the basis of spectral analysis and identified as ent-kaurene terpenoids (1–3), anthraquinones (4–8), flavonoids (9–12), steroids (13–15), and other compounds (16–33). Compound 1–14, 19–27 were isolated from the genus osmunda for the first time. Compound 28–29 were isolated from the plant for the first time. Cytotoxicities of all compounds against Hela, HepG2 and A549 cell lines were measured by MTT assay, and their antioxidant activities were determined by DPPH and ABTS radical scavenging assays. Compound 2 exhibited potent cytotoxicity against Hela, HepG2 cell lines with IC₅₀ values of 9.31 and 9.66?μM, respectively. Compound 9 showed good antioxidant activity. The Trolox-equivalent antioxidant capacity (TEAC) value was 0.95?mM in ABTS assay, and the IC₅₀ value was 18.63?μM in DPPH assay.     

Two new ent-atisanes from the root of Euphorbia fischeriana Steud.

Two new ent-atisanes ent-1β,3β,16β,17-tetrahydroxyatisane (1), ent-1β,3α,16β,17-tetrahydroxyatisane (2) together with 11 known diterpenes were isolated from the anti-tumour activity fraction of Euphorbia fischeriana Steud. The compounds were identified by detailed spectroscopic analysis, including extensive 2D-NMR experiments. X-ray analysis was applied to determine the structure of compound 2. All 13 compounds were screened for cytotoxicity in vitro against human tumour MCF-7, HepG-2 and SGC-7901 cell lines. Compounds 1 and 2 showed the inhibitory effects against MCF-7 with IC₅₀ levels of 23.21 and 15.42 μM; simultaneously, compounds 4, 6, 8 and 11 also had definite inhibitory effect against different cell lines.     

Two new 5,6-epoxysterols from calcareous marine sponge Leucetta chagosensis

Chemical investigation on CH₂Cl₂ extract of the marine sponge Leucetta chagosensis, collected from the South China Sea, afforded two new 5,6-epoxysterols, 5α,6α-epoxycholesta-8(14),22(E)-diene-3β,7α-diol (1) and (24R)-24-ethyl-5α,6α-epoxycholesta-8(14),22(E)-diene-3β,7α-diol (2) along with ten known related steroid analogs (3–12). Their structures were elucidated on the basis of NMR spectroscopic analyses, and comparison with the literature. All isolates were tested for cytotoxicity against three tumor cell lines only known compounds 11 and 12 exhibited notable cytotoxic activity against A549 (IC₅₀: 3.0 and 5.6?μM), PC9 (2.0 and 15.6?μM), and MCF-7 (9.4 and 11.8?μM) cell lines, respectively.     

Cytotoxic triquinane-type sesquiterpenoids from the endophytic fungus Cerrena sp. A593

Abstract

The culture broth of Cerrena sp. A593, which was isolated from Pogostemon cablin, showed potent cytotoxicity against several human tumor cell lines. The following chemical study resulted in the isolation of two new triquinane-type sesquiterpenoids, named cerrenins D (1) and E (2), along with two known compounds plerocybellone A (3) and chloriolin B (4). Their structures were fully assigned with the aid of extensive spectroscopic analysis (¹H and ¹³C NMR, HSQC, HMBC, ¹H-¹H COSY, HRESIMS, and IR) and data from the literature. Moreover, cytotoxic activity in vitro of compounds 1–4 were evaluated against SF-268, MCF-7, NCI-H460, and HepG-2 tumor cell lines. The new compound 1 exhibited weak growth inhibitory activity against all the four tumor cell lines with IC₅₀ values of 41.01, 14.43, 29.67, 44.32?μM.     

Lactoquinomycin C and D,two new medermycin derivatives from the marine-derived Streptomyces sp. SS17A

Abstract

Lactoquinomycin C (1) and Lactoquinomycin D (2), two new medermycin derivatives together with six known compounds (3–8) were isolated from the rice solid fermentation of the marine-derived Streptomyces sp. SS17A. The intriguing structural features of the Lactoquinomycin D (2) which contains 5,14-epoxidation is relatively rare in medermycin derivatives. Compounds 1 and 2 exhibited no cytotoxicity against PC-3 and HCT-116 cancer cell lines, whereas compound 3 showed stronger cytotoxicity with IC₅₀ values of 0.02 and 0.04?μM, respectively. A structure-activity relationship was observed for the cytotoxicity of the medermycin derivatives with a γ-lactone unit is required for significant cytotoxicity based on compounds 1–3.     

Convenient synthesis and antitumor evaluation of some new 9-ethyl-3-(hetaryl)carbazoles

Abstract

In continuing our efforts to develop new potent anticancer candidates, a new series of 9-ethylcarbazoles carrying at position 3 various heterocyclic substituents such as 2-imino-2H-chromenes 5a–e, 2-oxo-2H-chromenes 6a–e, 3-imino-3H-benzo[f]chromene 8, 3-oxo-3H-benzo[f]chromene 9, 2-pyridones 11, 14, pyrazole 19, pyrimidine 23, pyrido[1,2-a]pyrimidine 27, 2H-pyran-2-one 30, and pyrano[2,3-d]pyrimidinetrione 34 were efficiently synthesized, characterized and evaluated for their in vitro antitumor activity. The mechanism for the synthesis of compounds was also discussed. Most of the synthesized compounds were displayed the considerable anticancer activities against three human tumor cells lines, in particular, colon carcinoma (HCT-116), hepatocellular carcinoma (HepG-2) and breast cancer (MCF-7). Compound 6d proves as most active molecule in this study with special effectiveness against the human HCT-116 and HepG-2 as its IC₅₀ values are 1.50, 0.90?μM, respectively, when doxorubicin is compared. Compound 34 was also found to have high activity against HepG-2, HCT-116 and moderate activity against MCF-7.     

A new cytotoxic biflavonoid from the rhizome of Wikstroemia indica

One new chalcone-flavone biflavonoid, 3′-hydroxydaphnodorin A (1), together with 12 known biflavonoids (2–13), was isolated from the rhizome of Wikstroemia indica. Their structures were established on the basis of extensive spectroscopic methods. Eight isolated compounds 1–3, 6, 7, 9, 12 and 13 were evaluated for their cytotoxic activities against cancer-derived cell lines Hep3B, HepG2 and CNE2, and 1 was found to possess moderate cytotoxicity against HepG2 and CNE2 cell lines, with IC₅₀ values of 65.5 ± 11.4 and 53.6 ± 10.1 μM, respectively.     

A new abietane diterpenoid glycoside from ajuga ovalifolia var. calantha

A new abietane diterpenoid glycoside, ajugaside B (1), along with three known compounds (2–4), were isolated from the whole plants of Ajuga ovalifolia var. calantha. The structure of the new compound (1) was elucidated by means of spectroscopic analyses (HRESIMS, IR, NMR and ECD). All of the isolated compounds were evaluated for their antitumor activities against MGC803, MCF-7, A549, HT29 and HepG2 cell lines. Compounds 3–4 showed moderate cytotoxicity against all tested cell lines with IC₅₀ values of 1.8–7.3?μM.     

A new phenolic compound from Phedimus middendorffianus with antiproliferative activity

Abstract

A new phenolic compound (1) and together with 12 known compounds–eight flavonoids (2?～?9), two phenolic compounds (10 and 11) and two benzoic acid (12 and 13)–were isolated from Phedimus middendorffianus (Maxim.). The structures of all compound were determined on the basis of spectroscopic (MS and NMR) analyses. Compounds 4, 5, 7 and 11?～?13 were showed anti-proliferative activities against MCF-7 than PC-3 cell line. Also compound 12 and 13 showed the significant cytotoxic activities against two cancer cell lines, PC-3 and MCF-7.     

A new 5-alkylresorcinol glucoside derivative from Cybianthus magnus

One new 5-alkylresorcinol glucoside (1) was isolated from leaves of Cybianthus magnus, along with 12 known compounds, isolated from four plants belonging to Myrsinaceae family (2, 3 isolated from C. magnus; 4–7, 10 and 11 isolated from Myrsine latifolia; 4, 8 and 9 isolated from Myrsine sessiflora; 6, 7, 10, 12 and 13 isolated from Myrsine congesta). Their structures were determined on the basis of spectroscopic analysis and by comparison of their spectral data with those reported in the literature. So far, only nine 5-alkylresorcinol glucosides were isolated from leaves of Grevillea robusta. Since resorcinols are known to exhibit strong cytotoxic activity, compounds 1 and 2 were tested against cell lines 3T3, H460, DU145 and MCF-7 for cytotoxicity in vitro and compounds 3–13 were tested for their antileishmanial activity. Compound 2 displayed a strong cytotoxic activity with IC₅₀ values ranging between 22 and 100 μM for all tested cell lines. Compounds 3–13 were not active against Leishmania amazonensis amastigotes.     

Macrocyclic bis-quinolizidine alkaloids from Xestospongia muta

A new stereoisomer Meso-araguspongine C together with nine reported macrocyclic bis-quinolizidine alkaloids araguspongines A, C, E, L, N?P, petrosin, and petrosin A were isolated from marine sponge Xestospongia muta. Stereochemistry of meso-araguspongine C (2) and araguspongines N-P (3?5) were established by their NMR data and conformational analyses. Both araguspongine C (1) and meso-araguspongine C (2) exhibited great cytotoxic activity towards HepG-2, HL-60, LU-1, MCF-7, and SK-Mel-2 human cancer cells (IC₅₀ in the range of 0.43–1.02 μM). At a concentration of 20 μM, isolated compounds (1?10) also showed modest inhibitory effects (from 7.6 to 40.8%) on the NO production in LPS activated RAW264.7 macrophages.     

New cucurbitane-type triterpenoid glucosides from the tubers of Hemsleya amabilis with anti-tumor activity

Abstract

Two new cucurbitane-type triterpenoid glucosides, 3β,11α-dihydroxycucurbita-5,24(E)-diene-3,26-glucosides (1) and 3β,11α-dihydroxycucurbita-5,24(Z)-diene-3,27-glucosides were isolated from the tubers of Hemsleya amabilis. Their structures were elucidated by various spectroscopic techniques including IR, HRESIMS, 1D and 2D NMR. The two compounds were evaluated for their anti-tumor activity against HeLa and HepG-2 cell lines, and both displayed moderate anti-tumor activity towards HeLa cell lines with IC₅₀ values of 9.8 and 15.7?μM, respectively.     

Synthesis,characterization and biological evaluation of some novel sulfonylthiosemicarbazides

Abstract

A series of thiosemicarbazides were synthesized and structurally characterized by spectroscopic techniques (NMR, FT-IR) besides elemental analysis. These compounds were evaluated for their cytotoxicity against human breast cancer cell line MCF7 and prostate cancer cell line PC3 and nonmalignant fibroblast L929 cell line by MTT assay. Among the compounds, N-[2-(4-chlorophenyl)ethyl]-2-[(4-methylphenyl)sulfonyl]hydrazinecarbothioamide (3d) and 2-[(4-methylphenyl)sulfonyl]-N-[4-(trifluoromethoxy)phenyl]hydrazinecarbothioamide (3f) were found to display significant cytotoxicity with IC₅₀ of 13.87?μM (against PC3 cell line) and 1.47?μM (against MCF7 cell line), respectively. These compounds were non-cytotoxic to normal cell line with IC₅₀>100?μM. Western blotting studies demonstrated that compound 3f induced apoptosis and caused cell death in the MCF7 and PC3 cell lines via an increase in Bax protein expression and a slight decrease in Bcl-2 protein expression. The gene expression ratio Bax/Bcl-2 showed the induction of mitochondrial apoptosis in cancer cell lines. All of synthesized compounds have also been tested for antioxidant activity and all compounds achieved strong inhibition of the DPPH radical. These findings showed that compound 3f, displays potential to be further explored in the development of new anticancer agents.     

Cytotoxicity and Synergistic Effect of the Constituents from Roots of Aglaia odorata (Meliaceae)

Twelve compounds were isolated from the roots of Aglaia odorata. Their structures were established on the basis of NMR and MS data as rocaglaol (1), rocaglamide (2), eichlerialactone (3), sapelins A (4), isofouquierone (5), eichlerianic acid (6), shoreic acid (7), agladupol E (8), 3-epimeliantriol (9), cleomiscosins B (10), 2β,3β-dihydroxy-5α-pregnane-16-one (11) and β-d-glucopyranos-1-yl N-methylpyrrole-2-carboxylate (12). Among them, compounds 1 and 2 showed significant cytotoxicity against human cancer cell (HL-60, SMMC-7721, A-549, MCF-7 and SW480) with IC₅₀ values of 0.007–0.095 μM, while compounds 3–5 and 10 and 11 showed moderate to no cytotoxicity (IC₅₀ 0.43 to values >40 μM). Compound 6 showed only weak cytotoxicity (IC₅₀ 6.87 to >40 μM) and its epmier 7 was completely inactivite (IC₅₀>40 μM) in the assay. However, potent synergistic effect was observed when the molar ratio of 6 to 7 is between 4:1 and 1:1.     

A new monoterpene glucoside and complete assignments of dihydroflavonols of Pulicaria jaubertii: potential cytotoxic and blood pressure lowering activity

One new monoterpene glucoside and five dihydroflavonols were isolated for the first time from the aerial parts of Pulicaria jaubertii and identified as p-menthane-2-O-β-D-glucopyranoside [1], dihydroquercetin (taxifolin) [2], 7,3′-di-O-methyltaxifolin [3], 3′-O-methyltaxifolin [4], 7-O-methyltaxifolin (padmatin) [5] and 7-O-methyl-dihydrokampferol (7-O-methylaromadenderin) [6]. The structures of these compounds were unambiguously assigned on the basis of NMR spectroscopic data (¹H, ¹³C, DEPT, HSQC, HMBC) and MS analysis. 2D-NMR methods required revision of assignments of H-6 and H-8 for dihydroflavonol compounds. Possible cytotoxic activity as well as blood pressure (BP) lowering activity were tested. The alcoholic extract showed cytotoxic activity against prostate carcinoma (PC-3), breast carcinoma (MCF-7) and hepatocellular carcinoma (HepG-2) human cell lines with IC₅₀ 19.1, 20.0 and 24.1 μg, respectively. The higher dose levels of the alcoholic extract significantly reduced normal BP of rats in a dose-dependent manner.     

Design and synthesis of novel 7-[(N-substituted-thioureidopiperazinyl)-methyl]-camptothecin derivatives as potential cytotoxic agents

Abstract

As part of continuing our research on diverse C-7 derivatives of camptothecin (CPT), 16 CPT derivatives bearing piperazinyl-thiourea chemical scaffold and different substituent groups have been designed, synthesized and evaluated in vitro for cytotoxicity against five tumor cell lines (A-549, MDA-MB-231, MCF-7, KB and KBvin). As a result, all the synthesized compounds showed promising in vitro cytotoxic activity against the five tumor cell lines tested, and were more potent than irinotecan. Importantly, compounds 13?g (IC₅₀ = 0.514?μM) and 13o (IC₅₀ = 0.275?μM) possessed similar or better antiproliferative activity against the multidrug-resistant (MDR) KBvin subline than that of topotecan (IC₅₀ = 0.511?μM) and merit further development as anticancer candidates for clinical trail. With these results in hand, we have a reason to conclude that incorporating piperazinyl-thiourea motifs into position-7 of camptothecin confers well cytotoxic activity against cancer cell lines, probably resulting in new anticancer drugs.     

(–)-β-Homoarginine anhydride,a new antioxidant and tyrosinase inhibitor,and further active components from Trichosanthes truncata

Abstract

One new amino acid derivative, (–)-β-homoarginine anhydride 1, as well as nine known compounds were isolated from Trichosanthes truncata. The structures of the isolates were elucidated by spectroscopic methods. Among them, compounds 5 and 11 could notably dose-dependently inhibit ROS productions in HaCaT keratinocyte cells without cytotoxicity in the concentration range of 0.2–20?μM. In cell-free mushroom tyrosinase assay, compounds 1–5, 10 and 11 had more potential anti-tyrosinase activities with IC₅₀ values of 106.9–255.6?μM than arbutin that were similar to predicted values of binding affinity calculated by molecule docking. The most active 2 had hydrogen bonds (Ser77, Glu309, Phe454) and electrostatic charges (Glu309, Glu248) interactions with mushroom tyrosinase, respectively. Our data manifested that T. truncata and its components are potentially to be developed as anti-aging and whitening agents for skin disorders.     

New cytotoxic bufadienolides from the roots and rhizomes of Helleborus thibetanus Franch

Abstract

Three new bufadienolides 14β, 16β-dihydroxy-3β-[β-D-glucopyranosyl-(1→6)-(β-D-glucopyranosyl)oxy]-5α-bufa-20, 22-dienolide (1), 14β-hydroxy-3β-[β-D-glucopyranosyl-(1→4)-(β-D-glucopyranosyl)oxy]-5α-bufa-20, 22-dienolide (2) and hellebrigenin-3-O-β-D-glucosyl-(1→4)-β-D-glucoside (3), together with eight known bufadienolides (4–11) were isolated from the roots and rhizomes of Helleborus thibetanus. Their structures were elucidated by extensive spectroscopic methods and acid hydrolysis. Compounds 1–7 were evaluated for their cytotoxic activity against HCT116, A549 and HepG2 tumor cell lines. Compound 1 exhibited moderate cytotoxicity against HepG2 cells with IC₅₀ value of 15.1?±?1.72?μM. Compounds 5 and 6 exhibited moderate cytotoxicity against HCT116 cells with IC₅₀ values of 15.12?±?0.58?μM and 13.17?±?2.34?μM, respectively.