Cytotoxic and antimicrobial aporphine alkaloids from Fissistigma poilanei (Annonaceae) collected in Vietnam

Two new aporphine alkaloids: 8-hydroxy-9-methoxy-1,2-methylenedioxyaporphine (1) and 8-hydroxy-3,9-dimethoxy-1,2-methylenedioxyaporphine (2) were isolated from the ethyl acetate extract of Fissistigma poilanei along with five known compounds: oxocrebanine (3), kuafumine (4), (2R,3R)-3',4',5,7-tetrahydroxydihydroflavonol-3-O-α-L-rhamnopyranoside (5), (+)-catechin 3-O-α-L-rhamnopyranoside (6) and quercetine 3,7-dimethoxy-3'-O-α-L-rhamnopyranosyl-(1?→?2)-β-D-glucopyranoside (7). These two new aporphine alkaloids exhibited a moderate cytotoxic activity against four human cancer cell lines (KB, Hep-G2, MCF-7, LU) as well as antimicrobial activity against Lactobacillus fermentum, Enterococcus faecium, Staphylococcus aureus and Bacillus subtillis.     

Two new diterpenoids from the buds of Wikstroemia chamaedaphne

Two new diterpenoids, wikstroelide Q (1) and prostratin Q (5), together with three known diterpenoids, pimelea factors P? (2), P? (3), and prostratin (4), and five known lignans, (+)-epipioresinol (6), (+)-isolariciresinol (7), (?)-lariciresinol (8), (+)-epi-sesaminone (9), and prestegane B (10), were isolated from the buds of Wikstroemia chamaedaphne Meissn. Their structures were elucidated by a combination of spectroscopic analyses. Compounds 1–10 were evaluated for their cytotoxicities against HL-60, SMMC-7721, A549, MCF-7, SW480, and BEAS-2B cell lines in vitro.     

Cytotoxic cassane diterpenoids from the seeds of Caesalpinia sappan

Phytochemical investigation on the seeds of Caesalpinia sappan led to the isolation of five new cassanetype diterpenoids, named 11-oxo-phanginin A(1), caesalsappanins O–Q(2–4) and phanginin U(5),together with five known compounds. The structures of the new compounds were elucidated by extensive analysis of mass spectrometric and 1D and 2D NMR spectroscopic data. All the new compounds showed moderate cytotoxic effects on human breast cancer MCF-7 and human colon cancer HCT116 cell lines.     

Two new aryltetralin lignans from the roots of Dolomiaea souliei

Two new aryltetralin-type lignans, dolomiaeasin A (1) and dolomiaeasin B (2), were isolated from the roots of Dolomiaea souliei. Their structures were elucidated by means of various spectroscopic analyses. The cytotoxicities of 1 and 2 were tested by the MTT method, and both compounds showed no significant cytotoxic activities against the A549 and A2780 human cancer cell lines. This is the first time that aryltetralin-type lignans were isolated from the genus Dolomiaea.     

Phytochemical and cytotoxic investigations of Curcuma mangga rhizomes

Investigations on the cytotoxic effects of the crude methanol and fractionated extracts (hexane, ethyl acetate) C. mangga against six human cancer cell lines, namely the hormone-dependent breast cell line (MCF-7), nasopharyngeal epidermoid cell line (KB), lung cell line (A549), cervical cell line (Ca Ski), colon cell lines (HCT 116 and HT-29), and one non-cancer human fibroblast cell line (MRC-5) were conducted using an in-vitro neutral red cytotoxicity assay. The crude methanol and fractionated extracts (hexane and ethyl acetate) displayed good cytotoxic effects against MCF-7, KB, A549, Ca Ski and HT-29 cell lines, but exerted no damage on the MRC-5 line. Chemical investigation from the hexane and ethyl acetate fractions resulted in the isolation of seven pure compounds, namely (E)-labda-8(17),12-dien-15,16-dial (1), (E)-15,16-bisnor-labda-8(17),11-dien-13-on (2), zerumin A (3), β-sitosterol, curcumin, demethoxycurcumin and bis-demethoxycurcumin. Compounds 1 and 3 exhibited high cytotoxic effects against all six selected cancer cell lines, while compounds 2 showed no anti-proliferative activity on the tested cell lines. Compound 1 also demonstrated strong cytotoxicity against the normal cell line MRC-5. This paper reports for the first time the cytotoxic activities of C. mangga extracts on KB, A549, Ca Ski, HT-29 and MRC-5, and the occurrence of compound 2 and 3 in C. mangga.     

Design and synthesis of alepterolic acid and 5-fluorouracil conjugates as potential anticancer agents

Conjugates of alepterolic acid with 5-fluorouracil derivatives have been synthesized in 70–90% yields. The cytotoxic evaluation against two human cancer cell lines, viz. MCF-7 (breast) and A549 (lung), using MTT assay showed anticancer activities of the obtained compounds.     

Two new terpenoids from endophytic fungus Periconia sp. F-31

Two new terpenoids, (+)-(3S,6S,7R,8S)-periconone A (1) and (-)-(1R,4R,6S,7S)-2-caren-4,8-olide (2), have been isolated from an endophytic fungus Periconia sp., which was collected from the plant Annona muricata. Their structures were elucidated on the basis of extensive spectroscopic analyses. In the in vitro assays, the two compounds showed low cytotoxic activities against six human tumor cell lines (HCT-8, Bel-7402, BGC-823, A549, A2780 and MCF-7) with IC(50)>10(-5) M.     

Two new eupodienone lignans from Gymnotheca chinensis

Two new eupodienone lignans, named gymnothelignan T(1) and gymnothelignan U(2) were isolated from the whole plants of endemicmedicinal plant of Gymnotheca chinensis(Saururaceae). The structures of the new compounds were elucidated by means of HRMS, 1D and 2D NMR. Compound 1 was tested for cytotoxic activity in HCT15, HCT116, A549, MCF-7 and HepG2 cells and exhibited no appreciable activity against these tested cell lines with IC50 values above 50 mmol/L.     

Synthesis,Characterization, In Vitro Anticancer Potentiality,and Antimicrobial Activities of Novel Peptide–Glycyrrhetinic-Acid-Based Derivatives

Glycyrrhetinic acid (GA) is one of many interesting pentacyclic triterpenoids showing significant anticancer activity by triggering apoptosis in tumor cell lines. This study deals with the design and synthesis of new glycyrrhetinic acid (GA)–amino acid peptides and peptide ester derivatives. The structures of the new derivatives were established through various spectral and microanalytical data. The novel compounds were screened for their in vitro cytotoxic activity. The evaluation results showed that the new peptides produced promising cytotoxic activity against the human breast MCF-7 cancer cell line while comparing to doxorubicin. On the other hand, only compounds 3, 5, and 7 produced potent activity against human colon HCT-116 cancer cell line. The human liver cancer (HepG-2) cell line represented a higher sensitivity to peptide 7 (IC₅₀; 3.30 μg/mL), while it appeared insensitive to the rest of the tested peptides. Furthermore, compounds 1, 3, and 5 exhibited a promising safety profile against human normal skin fibroblasts cell line BJ-1. In order to investigate the mode of action, compound 5 was selected as a representative example to study its in vitro effect against the apoptotic parameters and Bax/BCL-2/p53/caspase-7/caspase-3/tubulin, and DNA fragmentation to investigate beta (TUBb). Additionally, all the new analogues were subjected to antimicrobial assay against a panel of Gram-positive and Gram-negative bacteria and the yeast candida Albicans. All the tested GA analogues 1–8 exhibited more antibacterial effect against Micrococcus Luteus than gentamicin, but they exhibited moderate antimicrobial activity against the tested bacterial and yeast strains. Molecular docking studies were also simulated for compound 5 to give better rationalization and put insight to the features of its structure.     

Phragmalin-type limonoid orthoesters from Chukrasia tabularis var. velutina

Nine new phragmalin-type limonoid orthoesters, tabulalides F-N (1-9), together with three known compounds, tabulalides C and D, and tabularisin N (10-12), were isolated from the stem bark of Chukrasia tabularis var. velutina. Extensive spectroscopic technologies were applied to elucidate the structures of these new compounds, including the application of circular dichroism (CD) exciton chirality method for the determination of the absolute configurations of 1 and 2. Tabulalide F (1) has a rare orthoisobutylate moiety in phragmalin-type limonoid orthoesters. These compounds were evaluated for cytotoxic activity against five human cancer cell lines in vitro. Tabulalide G (2) exhibits moderate cytotoxic activity against MCF-7 with IC(50) value of 20.4 μmol/l, and other compounds have weak inhibitory effects on the growth of tested tumor cells.     

Two new lignans from the stem bark of Magnolia obovata and their cytotoxic activity

Two new lignans, 4-methoxymagnaldehyde B (1) and coumanolignan (2), were isolated from the stem bark of Magnolia obovata, together with 11 known compounds (3-13). The structures of compounds 1 and 2 were determined to be 5'-allyl-2'-hydroxyphenyl-4-methoxy-3-cinnamic aldehyde (1) and 6-allyl-8-(5'-allyl-2'-hydroxyphenyl)coumarin (2) on the basis of spectroscopic and physicochemical analyses including 2D NMR and high-resolution EI-MS. Compounds 1-8, 11, 12, and 13 were tested in vitro for their cytotoxic activities against the HeLa, A549, and HCT116 cancer cell lines. Among the compounds tested, compound 1 showed the strongest cytotoxic activity against the HCT116 cancer cell line, with an IC(50) value of 1.3 microg/ml.     

Design,Synthesis, Biological Evaluation and Silico Prediction of Novel Sinomenine Derivatives

Sinomenine is a morphinan alkaloid with a variety of biological activities. Its derivatives have shown significant cytotoxic activity against different cancer cell lines in many studies. In this study, two series of sinomenine derivatives were designed and synthesized by modifying the active positions C₁ and C₄ on the A ring of sinomenine. Twenty-three compounds were synthesized and characterized by spectroscopy (IR, ¹H-NMR, ¹³C-NMR, and HRMS). They were further evaluated for their cytotoxic activity against five cancer cell lines, MCF-7, Hela, HepG2, SW480 and A549, and a normal cell line, Hek293, using MTT and CCK8 methods. The chlorine-containing compounds exhibited significant cytotoxic activity compared to the nucleus structure of sinomenine. Furthermore, we searched for cancer-related core targets and verified their interaction with derivatives through molecular docking. The chlorine-containing compounds 5g, 5i, 5j, 6a, 6d, 6e, and 6g exhibited the best against four core targets AKT1, EGFR, HARS and KARS. The molecular docking results were consistent with the cytotoxic results. Overall, results indicate that chlorine-containing derivatives might be a promising lead for the development of new anticancer agents.     

Synthesis and Biological Evaluation of a Novel Series of Chalcones Incorporated Pyrazole Moiety as Anticancer and Antimicrobial Agents

A newly synthesized series of chalcone derivatives containing pyrazole rings were synthesized and evaluated for their cytotoxic activities in vitro against several human cancer cell lines. Most of the prepared compounds showed potential cytotoxicity against human breast cancer cell lines MCF-7, HEPG-2, and HCT-116. Also the compounds were evaluated as antimicrobial agents. The three compounds 3, 4, and 5 were proved to be better anticancer agents than the positive standard doxorubicin with IC50 values (4.7, 4.4, and 3.9???g/ml) against the same human cancer cell lines, whereas compounds 5 and 6 showed the most active antimicrobial compounds in comparison to the other chalcones.     

Synthesis of chalcones with anticancer activities

Several chalcones were synthesized and their in vitro cytotoxicity against various human cell lines, including human breast adenocarcinoma cell line MCF-7, human lung adenocarcinoma cell line A549, human prostate cancer cell line PC3, human adenocarcinoma cell line HT-29 (colorectal cancer) and human normal liver cell line WRL-68 was evaluated. Most of the compounds being active cytotoxic agents, four of them with minimal IC?? values were chosen and studied in detail with MCF-7 cells. The compounds 1, 5, 23, and 25 were capable in eliciting apoptosis in MCF-7 cells as shown by multiparameter cytotoxicity assay and caspase-3/7, -8, and -9 activities (p < 0.05). The ROS level showed 1.3-fold increase (p < 0.05) at the low concentrations used and thus it was concluded that the compounds increased the ROS level eventually leading to apoptosis in MCF-7 cells through intrinsic as well as extrinsic pathways.     

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.     

Chemical constituents of the ethyl acetate extract of Belamcanda chinensis (L.) DC roots and their antitumor activities

An activity-directed fractionation and purification process was used to isolate antitumor compounds from the roots of Belamcanda chinensis (L.) DC. The ethyl acetate extract showed greater antitumor activities than the other extracts, consequently leading to the isolation of 18 compounds identified as β-sitosterol (1), dausterol (2), quercetin (3), kampferol (4), shikimic acid (5), gallic acid (6), ursolic acid (7), betulin (8), betulonic acid (9), betulone (10), tectoridin (11), irisflorentin (12), 4′,5,6-trihydroxy-7-methoxyisoflavone (13), tectorigenin (14), irilins A (15), iridin (16), irigenin (17), and iristectongenin A (18). Compounds 3-10, 13, and 15 were isolated from B. chinensis for the first time. Compounds 4 and 7-10 showed potent cytotoxic activities against PC3, MGC-803, Bcap-37, and MCF-7 cell lines. The mechanism of the antitumor action of compound 7 was preliminarily investigated through acridine orange/ethidium bromide (AO/EB) staining, Hoechst 33258 staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, which indicated the growth inhibition of MGC-803 cells via the induction of tumor cell apoptosis.     

Synthesis, characterization and in vitro cytotoxicity of pentacoordinated Tin(IV) complexes derived from aminoalcohols

The synthesis of pentacoordinated Tin(IV) compounds derived from aminoalcohols is described. The compounds were characterized by IR, 1H-, 13C-, and 119Sn-NMR, the mass spectrometry exhibits molecular ions corresponding to monomeric species. All compounds were evaluated for in vitro cytotoxic activities against five human tumor cell lines, U251 (human glioblastoma), PC-3 (human prostatic adenocarcinoma), K-562 (human chronic myelogenous leukemia), HCT-15 (human colorectal adenocarcinoma), MCF-7 (human mammary adenocarcinoma). The cytotoxic evaluation revealed that all compounds possess higher cytotoxic potency than that of the cisplatin, which was used as reference. Additionally, MT2 cells (human T-lymphocytes) were also evaluated.     

Systematic phytochemical investigation of Abies spectabilis

Systematical phytochemical investigations on Abies spectabilis afforded 72 chemical constituents. On the basis of physical and spectroscopic data, including 1D and 2D homo- and heteronuclear NMR experiments (heteronuclear single quantum coherence (HSQC), (1)H-(1)H correlation spectroscopy (COSY), heteronuclear multiple bond connectivity (HMBC), and nuclear Overhauser effect spectroscopy (NOESY)), and by comparison with the literature references, they were identified as 3 triterpenoids, 23 diterpenoids, 1 sesquiterpenoid, 13 flavonoids, 12 lignans, and 20 other components. Among these compounds, three were identified as new including abieta-7,13-diene-12α-methoxy-18-oic acid (1), 7α-methoxy-dehydroabietic acid (2), and 5-hydroxy-6-methyl-7,4'-dimethoxyflavone-8-O-β-D-glucopyranoside (3). These three new compounds (1-3) and all the known terpenoids (4-28) were tested for cytotoxic activities against four tumor cell lines: A549, COLO-25, QGY-25, and THP-1. However, none of them showed a positive effect (IC??>100 μM).     

Synthesis and antitumor activities of novel bis-quinazolin-4(3H)-ones

With the aim of obtaining new antitumor agents, a series of bis-quinazolin-4(3H)-ones ( 3a-3 f ) were designed and synthesized. These products contain 4-oxo-1,2,3,4-tetrahydro-quinazoline and 3H-quinazolin-4-one moieties linked together via a propyl chain. Cytotoxic activities of 3a-3 f were evaluated against lung adenocarcinoma (A549), breast carcinoma (MCF-7) and ovarian cancer (SKOV3) cell lines using MTT method. Cisplatin was used as a positive control. Among the tested compounds 3a , 3b , and 3e showed the best cytotoxic activities against all cancerous cell lines with IC₅₀ values even less than cisplatin. Compounds 3d and 3f also showed desirable cytotoxic activities especially against A549 and MCF-7.     

The cytotoxic activities of imidazole derivatives prepared from various guanylhydrazone and phenylglyoxal monohydrate

Abstract

A series of imidazole derivatives were synthesized from two-component condensation reaction of phenylgloxal monohydrate with guanylhydrazone. They were characterized by spectroscopic and analytical techniques. The in vitro anticancer evaluation of these compounds was done on human breast cancer (MCF-7) and human liver cancer (HepG2) cell lines using the MTT assay method. Most of the newly synthesized compounds displayed cytotoxic activity against these cancerous cells. In fact, compounds 3a, 3e, and 3?h exhibited more cytotoxic activities than the positive control drugs, fluro-5, and irinocam, against the MCF-7 cell line. Almost all the compounds, except for three, 3b, 3d, and 3f, gave more cytotoxic results than cisplatin. Therefore, these compounds could be considered for further development as anticancer drug candidates.