Ingenine E,a new cytotoxic β-carboline alkaloid from the Indonesian sponge Acanthostrongylophora ingens

A new β-carboline alkaloid ingenine E (4), along with three known metabolites annomontine (1), acanthomine A (2), and 1,2,3,4-tetrahydronorharman-1-one (3) were isolated from the Indonesian marine sponge Acanthostrongylophora ingens. Their structure characterization was unequivocally carried out using one- and two-dimensional NMR spectroscopy, as well as high-resolution mass spectrometry. The cytotoxic activity of the isolated compounds was evaluated toward MCF7, A549, HCT116, PC12, and Hela cancer cell lines. Ingenine E (4) exhibited cytotoxic activity against MCF7, HCT116, and A549 cell lines with IC₅₀ values of 3.5, 0.67, and 2.15 μg/ml.     

Three new sesquiterpenes from the stems of Nicotiana tabacum and their bioactivities

Three new sesquiterpenes, methyl 4-isopropyl-7-methoxy-6-methylnaphthalene-1-carboxylate (1), methyl 2-hydroxy-4-isopropyl-7-methoxy-6-methylnaphthalene-1-carboxylate (2), and methyl 2-hydroxy-6-(hydroxymethyl)-4-isopropyl-7-methoxynaphthalene-1-carboxylate (3), together with three known sesquiterpenes (4–6), were isolated from the stems of Nicotiana tabacum. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. The results showed that compounds 2, 3, and 5 exhibited high anti-TMV activity with inhibition rates of 33.6, 35.8, and 36.7%. Compounds 1–6 showed weak inhibitory activities against some tested human tumor cell lines (NB4, A549, SHSY5Y, PC3, and MCF7) with IC₅₀ values in the range of 6.7–9.6 μM.     

Methyl chanofruticosinate type alkaloids from the aerial parts of Kopsia lancibracteolata Merr.

A chemical investigation on the 70% ethanol extract from the leaves and stems of Kopsia lancibracteolata Merr. resulted in the isolation of three new methyl chanofruticosinate type alkaloids, 12-hydroxyl prunifoline A (1), 12-hydroxyl prunifoline C (2), and N(4)-oxide prunifoline D (3). Structural elucidation of all the compounds was performed by spectral methods such as 1D- and 2D-NMR, IR, UV, and HR-ESI-MS. The isolated alkaloids were tested in vitro for cytotoxic potential against five tumor cell lines (BGC-823, HepG2, MCF-7, SGC-7901, and SK-MEL-2). As a result, alkaloid 3 exhibited significant cytotoxic activity against all tested tumor cell lines with IC₅₀ values from 7.2 to 8.9 μM.     

Isoflavanones from Desmodium oxyphyllum and their cytotoxicity

Two new isoflavanones, (3R)-7-hydroxy-4′-methoxy-5-methoxycarbonyl-isoflavanone (1) and (3R)-8-hydroxy-4′-methoxy-7-methoxycarbonyl-isoflavanone (2), together with seven known isoflavanones (3–9) were isolated from Desmodium oxyphyllum of the Leguminosae family. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compound 1 showed good cytotoxicity against NB4 and SHSY5Y cell lines with IC₅₀ values of 3.1 and 2.5 μM; compound 2 exhibited cytotoxicity against PC3 cell lines with a IC₅₀ value of 3.6 μM; compound 4 showed cytotoxicity against A549 and SHSY5Y cell lines with IC₅₀ values of 3.6 and 2.8 μM; and compound 5 displayed cytotoxicity against NB4, SHSY5Y, and MCF7 cell lines with IC₅₀ values of 2.6, 3.8, and 2.8 μM, respectively. Other compounds also showed moderate cytotoxicity for some tested cell lines with IC₅₀ values between 5.4 and 8.8 μM.     

Three new C-alkylated flavonoids from Desmodium oblongum

Three new C-alkylated flavonoids, 4′-hydroxy-8-isobutyryl-7-methoxy-6-methyl-flavone (1), 4′,7-dimethoxy-8-isobutyryl-6-methyl-flavone (2), and 4′,7-dimethoxy-8-isobutyryl-flavone (3), together with three know ones luteolin (4), kaemferol (5), and quercetin (6), were isolated from Desmodium oblongum. Their structures were elucidated by spectroscopic methods, including extensive 1D- and 2D-NMR techniques. Compound 1 showed cytotoxicity against NB4, SHSY5Y, and MCF7 cell lines with IC₅₀ values of 8.5, 6.5, and 7.8 μM; compound 2 showed cytotoxicity against SHSY5Y and PC3 cell lines with IC₅₀ values of 5.0 and 6.8 μM; compound 3 displayed cytotoxicity against SHSY5Y and MCF7 cell lines with IC₅₀ values of 6.4 and 9.4 μM, respectively.     

Synthesis and <Emphasis Type="Italic">in Vitro</Emphasis> cytotoxic activities of 2-alkyl-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-2,6-diazacyclopenta[<Emphasis Type="Italic">b</Emphasis>]anthracene-5,10-diones

A series of 2-alkyl-2,3-dihydro-1H-2,6-diazacyclopenta[b]anthracene-5,10-diones (4a–f) was synthesized and their in vitro cytotoxic activities were evaluated against six human cancer cell lines (HCT15, SK-OV-3, SNB19, A549, MCF7 and MCF7/ADR). They all appeared to be less potent than doxorubicin against all doxorubicin sensitive human cancer cell lines tested. However, these compounds retained considerable cytotoxic activity against the doxorubicin-resistant cell line MCF7/ADR, implying their therapeutic potential to treat doxorubicin-resistant tumors. The most active compound 4c was equipotent with doxorubicin against HCT15 cell line.     

New neo-clerodane diterpenoids from Scutellaria strigillosa with cytotoxic activities

Two new neo-clerodane diterpenoids, named scutestrigillosins D and E (1 and 2), were isolated from the whole plant Scutellaria strigillosa. Their structures were established on the basis of detailed physical data analyses. In vitro, two new compounds exhibited cytotoxic activities against four tumor cell lines (HONE-1, P-388, MCF7, and HT29), and gave IC₅₀ values in the range of 3.4–8.9?μΜ.     

Chemical constituents of the red alga Laurencia tristicha

Six new sesquiterpenes, 10-hydroxy-epiaplysin (1), 10-hydroxy-aplysin (2), 10-hydroxy-debromoepiaplysin (3), aplysin-9-ene (4), epiaplysinol (5) and debromoepiaplysinol (6), together with 13 known compounds (7–19), have been isolated from the red alga Laurencia tristicha. The structures of 1–6 were determined by spectroscopic methods including IR, EI-MS, HREI-MS, and 1D and 2D NMR techniques. All compounds were obtained from this species for the first time and were tested for cytotoxic activities against several human cancer cell lines including lung adenocarcinoma (A549), stomach cancer (BGC-823), hepatoma (Bel 7402), colon cancer (HCT-8) and HeLa cell lines. Compound 6 showed selective cytotoxicity against HeLa cell line with IC₅₀ 15.5 μM, cholest-5-en-3β,7α-diol (14) was toxic to all tested cell lines with IC₅₀ values of 16.8, 5.1, 0.5, 0.5, and 0.3 μM, respectively, and other compounds were inactive (IC₅₀>10 μg/ml).     

Triazenoindazoles and triazenopyrazolopyridines: Design,synthesis, and cytotoxic activity

Several triazenoindazoles 3a–e and triazinopyrazolopyridines 6a–i were prepared through the reaction of the corresponding 3-amino-4-chloroindazole and 3-aminopyrazolopyridine diazonium salts 2 and 5 with a number of secondary amines. All compounds were evaluated for their in vitro cytotoxic activity on three cell lines, HepG2, MCF7, and HeLa. Most compounds inhibited cell growth with IC₅₀ less than 0.1 μM. Compound 6d was the most potent, with an IC₅₀ of 0.03 μM against HepG2 and 0.05 μM against MCF7 and HeLa cells.     

Synthesis and Biological Evaluation of Some Novel Polysubstituted Pyrimidine Derivatives as Potential Antimicrobial and Anticancer Agents

Synthesis and evaluation of the antimicrobial and cytotoxic activity of two series of polysubstituted pyrimidines comprising the thioether functionality and other pharmacophores, reported to contribute to various chemotherapeutic activities are described. All newly synthesized compounds were subjected to in‐vitro antibacterial and antifungal screening. Out of the compounds tested, 18 derivatives displayed an obvious inhibitory effect on the growth of the tested Gram‐positive and Gram‐negative bacterial strains, with special effectiveness against the Gram‐positive strains. Compounds 1 , 2 , 6 , 7 , 9 , 10 , 11 , 21 , and 24 revealed remarkable broad antibacterial spectrum profiles. Among those, compounds 1 , 2 , 6 , 7 , 9 , and 24 exhibited an appreciable antifungal activity against C. albicans. Compound 2 proved to be the most active antimicrobial member identified here as it showed twice the activity of ampicillin against B. subtilis and the same activity of ampicillin against M. Luteus and P. aeruginosa together with a moderate antifungal activity. Further, eleven analogs were evaluated for their in‐vitro cytotoxic potential utilizing the standard MTT assay against a panel of three human cell lines: breast adenocarcinoma MCF7, hepatocellular carcinoma HePG2, and colon carcinoma HT29. The obtained data revealed that six of the tested compounds 1 , 3 , 7 , 12 , 13 , and 15 showed a variable degree of cytotoxic activity against the tested cell lines at both the LC₅₀ and LC₉₀ levels. Compound 7 proved to be the most active cytotoxic member in this study with special effectiveness against the colon carcinoma HT29 and breast cancer MCF7 human cell lines for LC₅₀ and LC₉₀. Thus, compounds 1 and 7 could be considered as possible dual antimicrobial‐anticancer agents.     

Leucanone A and naamine J,glycerol ether lipid and imidazole alkaloid from the marine sponge Leucandra sp.

Chemical investigation on CH₂Cl₂ extract of the marine sponge Leucandra sp. afforded two new compounds named leucanone A (1) and naamine J (2), together with eight known compounds (3–10). Their structures were elucidated on the basis of NMR spectroscopic analyses, and comparing with the literature. The cytotoxic activities of the compounds were evaluated against four cancer cell lines, and compound 2 showed mild cytotoxic activities against MCF-7, A549, HeLa, and PC9 cancer cell lines with IC₅₀ values in the range of 20.1–45.3 μM.     

Monoterpenoid indole alkaloids from Alstonia mairei and their cytotoxicity

Phytochemical investigation on the 70% ethanol extract of the leaves of Alstonia mairei resulted in the isolation of three new monoterpenoid indole alkaloids, alstomairines A–C (1–3), along with one known compound, alpneumine A (4). Structural elucidation of all the compounds was accomplished by spectral methods such as 1D and 2D NMR, IR, UV, and HRESIMS. The isolated compounds were tested in vitro for cytotoxic activities against four osteosarcoma cell lines. Consequently, alkaloids 2 and 3 exhibited cytotoxic activities for all tested tumor cell lines with IC₅₀ values from 9.2 to 13.0 μM.     

New cycloartanes and new iridoids from Dolichandrone spathacea collected in the mangrove forest of Soc Trang province,Vietnam

Abstract

Two new cycloartanes, named dolichandrone A (1) and dolichandrone B (2), as well as two new iridoids, named [6-O-[(E)-4-methoxycinnamoyl]-1β-hydroxy-dihydrocatalpolgenin (3) and 6-O-[(E)-4-methoxycinnamoyl]-1α-hydroxy-dihydrocatalpolgenin (4), together with four known iridoids (5–8), were isolated from the leaves and barks of Dolichandrone spathacea. Their structures were elucidated by means of extensive analysis of their HRESIMS, 1D and 2D NMR spectroscopic data. All of these compounds have been isolated for the first time from this plant. Compounds 1, 2, 5, and 7 were evaluated for their cytotoxic activity in vitro against four human cancer cell lines KB, Lu, HepG2, and MCF7. The results showed that only compound 2 exhibited a good cytotoxicity against KB cell line with IC₅₀ of 18.77 μM.     

N9- and N7-(Chloromethyl Phenymethyl)Chloropurine Derivatives from α, α'-Dichloroxylenes: Synthesis and Anticancer Activity

A series of ortho- meta- and para-N9-[(chloromethylphenyl)methyl]chloropurines 4-12 and N7-[(chloromethylphenyl)methyl]chloropurines 13-21 were obtained by the reaction of various substituted chloropurines with α,α'-dichloroxylenes. Compounds 4-21 were evaluated for cytotoxic activity against a panel NCI-H460 (lung), MCF7 (breast) and SF-268 (CNS) cancer cell lines. The ‘active’ compounds, which reduced growth of cancer cells to ca. 32% or less, have been evaluated in a full panel of 60 human cancer cell lines over a 5-log dose range at the National Cancer Institute. Several compounds have demonstrated growth inhibitory effects (GI₅₀) in a wide range of cancer cell lines. The 2,6-dichloropurines in this series (5, 8, 11, 14, 17 and 20) exhibited significant antineoplastic activity.     

Guanacastane-type diterpenoids from the insect-associated fungus Verticillium dahliae

Four new guanacastane-type diterpenoids, namely dahlianes A (1), B (2), C (3), and D (4), were isolated from cultures of Verticillium dahliae. Their structures were elucidated on the basis of extensive spectroscopic data analysis. Their absolute configurations were determined by a combination of Mo₂(OAc)₄-induced electronic circular dichroism experiment and Mosher ester method. In cytotoxicity evaluation against human tumor cell lines, compounds 2 and 3 exhibited significant cytotoxicities against MCF-7 cell lines with IC₅₀ values of 3.35 and 4.72 μM, respectively.     

Chemical constituents from the roots of Tripterygium wilfordii and their cytotoxic activity

In our ongoing search for bioactive constituents, a new sesquiterpene polyol ester, named triptersinine U (1), together with five known triterpenes (2–6) and seven sesquiterpene pyridine alkaloids (7–13), were isolated from the roots of Tripterygium wilfordii Hook. f. Their chemical structures were elucidated using extensive spectroscopic analyses, including 1D and 2D NMR, and HRESIMS, as well as comparison with previously reported data. Cytotoxic activities of all compounds 1–13 were evaluated against six human tumor cell lines (HepG2, Hep3B, Bcap37, U251, MCF-7 and A549) using the MTT in vitro assay. The results showed that triterpenes exhibited moderate cytotoxic activities toward the tested cell lines.     

Synthesis and biological evaluation of novel benzo[c]acridine‐diones as potential anticancer agents and tubulin polymerization inhibitors

A new series of novel benzo[c]acridine‐diones possessing pharmacophoric elements of antitubulins with central dihydropyridine bridge were designed and synthesized as potential anticancer agents and tubulin polymerization inhibitors. The cytotoxic activity of the synthesized compounds was evaluated against eight cancer cell lines including MCF‐7, A2780, HeLa, HepG2, DU145, A549, PC3, and LNCAP cancer cells and normal cells human umbilical vein endothelial cell (HUVEC) through 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide (MTT) assay, wherein β‐lapachone and combretastatin A‐4 were used as positive controls. Some of our compounds ( 4c and 4g ) showed significant cytotoxic activity on cancer cells with IC₅₀ values in the range of 5.23–24.32 μM. None of the synthesized compounds showed significant cytotoxicity on normal HUVEC cells. Among all investigated derivatives, compound 4g showed promising greater antiproliferative activity against all tested cancer cells with the highest sensitivity observed for the PC3 cell line. Results from the flow cytometry analysis of PC3 and MCF‐7 cancer cells treated with 4g showed an induced cell‐cycle arrest at G2/M, and therefore induced apoptosis which occurred at low concentration of test compound, whereas annexin V‐FITC/propidium iodide staining assay in the aforementioned cancer cell lines treated with 4g showed that 4g can cause necrosis in PC3 and MCF‐7 cancer cells at higher concentration. Compound 4g proved to be an inhibitor of tubulin polymerization in a mode similar to that of colchicine and in a dose‐dependent manner. Molecular docking studies of 4g into the colchicine‐binding site of tubulin exhibited a possible mode of interaction between this compound and tubulin.     

Cytotoxic gelsedine-type indole alkaloids from Gelsemium elegans

The ethanol extract of the leaves and branches of Gelsemium elegans afforded three new gelsedine-type indole alkaloids, 11-methoxy-14,15-dihydroxyhumantenmine (1), 11-methoxy-14,15-dihydroxy-19-oxogelsenicine (2), and 11-methoxy-14-hydroxygelsedilam (3), along with one known alkaloid 11-methoxy-14-hydroxyhumantenmine (4). The structures of isolated compounds were established based on 1D and 2D (¹H-¹H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high-resolution mass spectrometry. The isolated alkaloids were tested in vitro for cytotoxic potential against four laryngeal tumor cell lines including Hep-2, LSC-1, TR-LCC-1, and FD-LSC-1. As a result, compounds 1 and 4 exhibited some cytotoxic activities against all tested tumor cell lines with IC₅₀ values of 10.9–12.1 μM and 9.2–10.8 μM, respectively.     

Antioxidant and cytotoxic lignans from the roots of Bupleurum chinense

In the search for biologically active compounds from the roots of Bupleurum chinense D C., phytochemical investigation of its ethanol extract led to the isolation and identification of a new 8-O-4′ neolignan glucoside, saikolignanoside A (1), along with eight known lignans (2–9). Their structures were determined on the basis of IR, UV, HRESIMS, and NMR spectroscopic analyses. The antioxidant and cytotoxic effects of isolated compounds were evaluated in vitro. The isolated compounds (IC₅₀ > 200 μM) did not display 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. Whereas compounds 1–2, 5, 7, and 9 exhibited potent 2, 2′-azinobis(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging properties with IC₅₀ values ranging from 8.34 to 15.24 μM, while compounds 3–4, 6, 8 showed moderate properties. In addition, all compounds were evaluated for cytotoxicities against A549, HepG2, U251, Bcap-37, and MCF-7 cell lines. Compounds 5 and 9 (IC_50?相似文献   

Four new diterpenoids isolated from the Euphorbia rapulum

Four new diterpenoids named 1-epi-9-hydroxydepressin (1), 1-epi-8-hydroxydepressin (2), 2,13,9-trihydroxy-labda-8(17),12(E),14-triene (3) and tagalsin I (4) were isolated from Euphorbia rapulum. The structures of these compounds were elucidated by means of various spectroscopic methods. All the isolated compounds were evaluated for cytotoxic activities against HepG2, MCF-7, and C6 cell lines, and compound 4 showed moderate selective activity against MCF-7 cell line with an IC₅₀ value of 31.8 μM.