Design,semisynthesis and cytotoxic activity of novel ester derivatives of betulinic acid-1,2,4 oxadiazoles

Taking into consideration of the biological activity of betulinic acid derivatives containing a oxadiazole ring, the semisynthetic betulinic acid-1,2,4-oxadiazole esters (14–25) were synthesized starting from betulinic acid (1) and 5-(bromomethyl)-3-aryl-1,2,4-oxadiazoles (2–13) and final compounds were tested for cytotoxic activity on three human cancer cell lines in vitro. All tested compounds showed good cytotoxic activity. The structures of synthesized compounds are established based on infrared (IR), nuclear magnetic resonance (NMR), and mass spectrometry.     

A New Sesquiterpene Lactone from Tsoongiodendron Odorum Chun

Abstract

A new sesquiterpene lactone (1) was obtained from the cytotoxic fraction of 95% ethanol extract of root barks of Tsoongiodendron odorum Chun together with two known sesquiterpene lactones, costunolide (2) and parthenolide (3). The structure of 1 was elucidated as 5α, 6α, 7β, 10β-11α, 13-dihydro-4(15)-eudesmene-12, 6-olide on the basis of chemical and spectral evidence including X-ray diffraction analysis. Costunolide showed cytotoxic activity against human leukemia (HL-60) cell line. Parthenolide showed promising cytotoxic activities in vitro against HCT-8, Bel-7402, SKOV3, KB, HELA and EJ cell lines. Also, the cytotoxic ethyl acetate fraction of ethanol extract of the root barks from which three chemical components were isolated showed promising cytotoxic activities in vitro against KB, BGC-823, Bel-7402, HCT-8, HL-60 cell lines.     

甘草次酸C3、C30衍生物的合成及其体外抗肿瘤活性研究

目的设计并合成甘草次酸C3、C30衍生物,并对其体外抗肿瘤活性进行研究。方法以甘草次酸为先导化合物,对其C3位羟基、C30位羧基进行结构修饰,并采用SRB法对目标化合物进行体外抗肿瘤活性研究。结果设计合成了12个新型甘草次酸衍生物,并利用MS、1H-NMR及元素分析确证了结构;体外实验中,目标化合物对MCF-7和A549肿瘤细胞的抑制活性均明显强于甘草次酸,其中化合物GA-I1、GA-I2和GA-II1对MCF-7和A549两种细胞表现出很好的抑制活性,明显高于对照药吉非替尼。结论甘草次酸衍生物具有良好的抗肿瘤活性,值得进一步研究。     

Two new compounds from the broth of the marine fungus Penicillium griseofulvum Y19-07

Two new compounds, 4-hydroxyphenethyl methyl succinate (1) and 4-hydroxyphenethyl 2-(4-hydroxyphenyl)acetate (2), were isolated from the EtOAc extract of the broth of the marine fungus Penicillium griseofulvum Y19-07. Five known compounds were also obtained in this study. The structures of the new compounds were elucidated by 1D and 2D NMR spectroscopy and mass spectrometry. All of the isolates were evaluated for their scavenging properties toward the 2,2-diphenyl-1-picrylhydrazyl free radical by spectroscopic assays. Also, in the cytotoxicity assay of the two new compounds against HL-60 and PC-3 prostate cancer cell lines, compound 2 showed potential activity with an IC₅₀ value of 64.5 μM against human HL-60 cancer cells.     

Cytotoxic Compounds from Brucea mollis

Ten compounds, including soulameanone (1), isobruceine B (2), 9-methoxy-canthin-6-one (3), bruceolline F (4), niloticine (5), octatriacontan-1-ol (6), bombiprenone (7), α-tocopherol (8), inosine (9), and apigenin 7-O-β-D-glucopyranoside (10), were isolated from the leaves, stems, and roots of Brucea mollis Wall. ex Kurz. Their structures were determined using one-and two-dimensional NMR spectroscopy and mass spectrometry. All compounds were evaluated for their cytotoxic activity against KB (human carcinoma of the mouth), LU-1 (human lung adenocarcinoma), LNCaP (human prostate adeno-carcinoma), and HL-60 (human promyelocytic leukemia) cancer cell lines. Compound 2 showed significant cytotoxic activity against KB, LU-1, LNCaP, and HL-60 cancer cells with IC₅₀ values of 0.39, 0.40, 0.34, and 0.23 μg/mL, respectively. In addition, compounds 3 and 5 showed significant cytotoxic activity against KB, LU-1, LNCaP, and HL-60 cancer cells with IC₅₀ values around 1–4 μg/mL. Compounds 9-methoxycanthin-6-one (3) and niloticine (5) have been discovered for the first time from the Brucea genus.     

Pregnane glycosides from the bark of Marsdenia cundurango and their cytotoxic activity

Seven new pregnane glycosides (1–7) and eight known compounds (8–15) were isolated from the bark of Marsdenia cundurango (Asclepiadaceae). The structures of 1–7 were determined by spectroscopic analysis, including two-dimension NMR spectroscopy, chemical transformations, and chromatographic analysis of the hydrolyzed products. The isolated compounds 1–15 were evaluated for their cytotoxic activity against HL-60 human leukemia cells, A549 human lung adenocarcinoma cells, and TIG-3 normal human lung cells, including apoptosis-inducing activity of a representative pregnane glycoside in HL-60 cells.

     

Chemical constituents of the Annona glabra fruit and their cytotoxic activity

Abstract

Context: Traditional Chinese medicines have attracted increasing interest as potential sources of novel drugs with a wide range of biological and pharmacological activities. Annona glabra Linn (Annonaceae) is used in traditional medicine as an anticancer drug. Phytochemical investigation of this plant led to the isolation of acetogenins, ent-kauranes, peptides, and alkaloids. In addition, compounds exhibited anticancer, anti-HIV-reserve, and antimalaria.

Objective: Isolation, structure determination, and cytotoxic activity evaluation of compounds from the methanol extract from A. glabra fruits.

Materials and methods: Using chromatographic methods to isolate compounds from the A. glabra methanol extract. The cytotoxic activity of compounds was evaluated by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, compounds which showed significant cytotoxic activity were chosen for further study apoptosis characteristics.

Results: One new, (2E,4E,1′R,3′S,5′R,6′S)-dihydrophaseic acid 1,3′-di-O-β-d-glucopyranoside, and eight known compounds, (2E,4E,1′R,3′S,5′R,6′S)-dihydrophaseic acid 3′-O-β-d-glucopyranoside (2), icariside D₂ (3), icariside D₂ 6′-O-β-d-xylopyranoside (4), 3,4-dimethoxyphenyl O-β-d-glucopyranoside (5), 3,4-dihydroxybenzoic acid (6), blumenol A (7), cucumegastigmane I (8), and icariside B₁ (9), were isolated from the fruits of A. glabra. Icariside D₂ (3) was found to show significant cytotoxic activity on the HL-60 cell line with the IC₅₀ value of 9.0?±?1.0?µM and did not show cytotoxic activity on the Hel-299 normal cell line. The further test indicated that compound 3 induced apoptosis via alteration of expression of apoptosis-related proteins and decreased phosphorylation of AKT in HL-60 cells.

Discussion and conclusion: The results suggested that the constituents from A. glabra may contain effective compounds which can be used as anticancer agents.     

A novel 3,4-dihydronaphthalen-1(2H)-one with spiro-butyrolactone and a new isocoumarin isolated from the endophytic fungus Phoma sp. YN02-P-3

A novel 3,4-dihydronaphthalen-1(2H)-one with spiro-butyrolactone phomol (1) and a new isocoumarin phomasatin (2), together with two known compounds (3–4) were isolated from the solid culture of the endophytic fungus Phoma sp. YN02-P-3. Their structures including the absolute configurations were characterized on the basis of extensive 1D, 2D NMR (HSQC, HMBC, NOESY), MS, and CD spectral data. Compound 1 showed selective cytotoxic activity against HL-60 cell line with the IC₅₀ value of 29.05 μM.     

Indoloquinazoline alkaloids from Euodia rutaecarpa and their cytotoxic activities

Nine indoloquinazoline alkaloids (1–9) were isolated from the dried and nearly ripe fruits of Euodia rutaecarpa (Juss.) Benth. (Euodiae Fructus), along with limonin and β-sitosterol. Their structures were elucidated on the basis of their spectroscopic data. Among them, compounds 1 and 2 were new compounds and characterized as (7R,8S)-7-hydroxy-8-methoxy-rutaecarpine and (7R,8S)-7-hydroxy-8-ethoxy-rutaecarpine, respectively, and 1-hydroxy-rutaecarpine (3) and (7R,8S)-7,8-dihydroxy-rutaecarpine (4) were isolated from Euodiae Fructus for the first time. The nine indoloquinazoline alkaloids were evaluated for their cytotoxic activities against human promyelocytic leukemia HL-60 cells and human gastric carcinoma N-87 cells.     

Steroid constituents from the soft coral Sinularia microspiculata

A methanol extract of the soft coral Sinularia microspiculata revealed five sterols, including two new compounds. Using combined chromatographic and spectroscopic experiments, the new compounds were found to be 7-oxogorgosterol (1) and 16α-hydroxysarcosterol (2). Their structures were determined on the basis of spectroscopic data (¹H and ¹³C NMR, HSQC, HMBC, ¹H-¹H COSY, NOESY, and FT-ICR-MS) and by comparing obtained results to the values indicated in previous studies. Among the isolated compounds, 3 showed weak cytotoxic effects against HL-60 (IC_50? = 89.02 ± 9.93?μM) cell line, whereas 5 was weakly active against HL-60 (IC_50? = 82.80 ± 13.65?μM) and SK-Mel2 (IC_50? = 72.32 ± 1.30?μM) cell lines.     

Structure determination of two new C21 steroidal glycosides from Cynanchum komarovii

Abstract

Two new 13,14:14,15-disecopregnane-type C₂₁ steroidal glycosides, namely komarosides R (1) and S (2), along with four known compounds (3–6), were obtained from the 95% ethanol extract of the whole herbs of Cynanchum komarovii Al.Iljinski (Asclepiadaceae). The structures of new compounds were elucidated on the basis of 1D, 2D NMR spectroscopic data and acid hydrolysis. Compounds 1 and 2 showed potent inhibitory activities against human leukemia cell line (HL-60) with IC₅₀ values being 6.2 and 17.6 μM, respectively, compared to the positive control 5-fluorouracil (6.4 μM).     

Synthesis, chemical characterization of novel 1,3-dimethyl acridones as cytotoxic agents, and their DNA-binding studies

A series of new 1,3-dimethyl acridone derivatives were synthesized with different alkyl side chain (propyl and butyl) substitution at N¹⁰-position and highly basic amine groups at terminal end of alkyl side chain. All the synthesized molecules were screened for their cytotoxic activity against human breast adenocarcinoma (MCF-7) and human promyelocytic leukemia (HL-60) cell lines. DNA binding constants (K_i) of selected compounds were determined with calf-thymus DNA. Results showed that the molecules 7, 8, 10, 11, 12, 13, 14, and 15 exhibited good cytotoxic activity with IC₅₀ value <10 μM. Compound 14 having (β-hydroxyethyl) piperazine butyl side chain exhibited potent cytotoxic activity against MCF-7 cell line and DNA-intercalating properties. Examination of the relationship between lipophilicity and acridone derivatives showed poor correlation.     

Cytotoxic constituents from the seeds of Vietnamese Caesalpinia sappan

Abstract

Context: Caesalpinia sappan Linn. (Leguminosae) has been used in folk medicines for the treatment of many diseases. The heartwood of this plant contains various phenolic components with interesting biological applications; however, the chemical and biological potentials of the seed of this plant have not been fully explored.

Objective: This study identified the cytotoxic activity of compounds from the seeds of C. sappan.

Materials and methods: The methanol extract of the seed of C. sappan was suspended in H₂O and then partitioned with CH₂Cl₂, EtOAc, and n-BuOH, successively. Diterpenoid compounds were isolated from the CH₂Cl₂-soluble fraction by silica gel column chromatography methods using organic solvents. The compound structures were determined by detailed analysis of NMR and MS spectral data. Cytotoxic activity was measured using a modified MTT assay against HL-60, HeLa, MCF-7, and LLC cancer cells. The activation of caspase-3 enzyme and western blotting assay were performed to confirm inhibitory mechanism of active compound.

Results: Five cassane-type diterpenoids were isolated and identified as phanginin I (1), phaginin A (2), phanginin D (3), phanginin H (4), and phanginin J (5). Compounds 1–4 showed effective inhibition against HL-60 cells with the IC₅₀ values of 16.4?±?1.5, 19.2?±?2.0, 11.7?±?1.6, and 22.5?±?5.1?μM. Compounds 1–3 exhibited cytotoxic activity against HeLa cells with the IC₅₀ values of 28.1?±?3.6, 37.2?±?3.4, and 22.7?±?2.8?μM. Treatment of HL-60 cell lines with various concentrations of 3 (0–30?μM) resulted in the growth inhibition and induction of apoptosis.

Conclusion: These findings demonstrate that compound 3 (phanginin D) is one of the main active components of the seed of C. sappan activating caspases-3 which contribute to apoptotic cell death.     

Hydroxyespintanol and schefflerichalcone: two new compounds from <Emphasis Type="Italic">Uvaria scheffleri</Emphasis>

A chemical investigation of the petroleum ether extract and chloroform extract of the root of Uvaria scheffleri Diels (Annonaceae) led to the isolation of two new compounds, named hydroxyespintanol (1) and schefflerichalcone (2), together with eight known compounds (3–10). The structural elucidation of compounds 1 and 2 by spectroscopic studies is described. The cytotoxicity of the isolated compounds against human promyelocytic leukemia HL-60 cells was studied. Among these, 2′-hydroxy-3′,4′,6′-trimethoxychalcone (5) exhibited cytotoxicity (IC₅₀ 12 μM), and espintanol (3), which was the main ingredient, also showed some cytotoxicity (IC₅₀ 44 μM).     

Synthesis and anticancer activity of para-xylyl linked bis-benzimidazolium salts and respective Ag(I) N-heterocyclic carbene complexes

The article describes synthesis, characterization (NMR, FT-IR, microanalysis, X-ray crystallography), and in vitro anticancer activity of para-xylyl linked bis-benzimidazolium salts and respective dinuclear Ag–NHC complexes. All the compounds were tested for their cytotoxicity against human colorectal cancer (HCT 116) and promyelocytic leukemia (HL-60) cell lines. According to cell viability measurements using MTT assay, all tested compounds showed dose-dependent cytotoxic activity against both cell lines. The tested compounds demonstrated significant activity with IC₅₀ values range 0.01–18.7 μM for HCT 116 and 0.7–55.7 μM for HL-60 cells. 5-Fluorouracil was used as standard drug (IC₅₀ 19.2 μM for HCT 116 and 5.4 μM for HL-60). We found that as the size of N-alkyl substitution on benzimidazolium salt increases its cytotoxicity decreases whereas a reverse occurred in case of respective complexes.     

Two new amides with cytotoxic activity from the fruits of Piper longum

Bioassay-guided fractionation of the fruits of Piper longum afforded two new minor amides, piperlongimin A (2) [2E-N-isobutyl-hexadecenamide] and piperlongimin B (4) [2E-octadecenoylpiperidine] together with five known compounds with moderate cytotoxic activity. The structures were elucidated on the basis of spectroscopic evidences. All these compounds inhibited cell proliferation of human leukemia, HL-60 cell lines, and displayed major apoptosis-inducing effects.     

Cytotoxic activity of Perilla frutescens var. japonica leaf extract is due to high concentrations of oleanolic and ursolic acids

Three triterpene acids, ursolic acid (1), corosolic acid (2), and oleanolic acid (7), were isolated from the ethanol extract of leaves of Perilla frutescens (L.) Britton var. japonica Hara (Labiatae; Japanese name: Egoma). These acids are the active principles responsible for the cytotoxicity against three cultured human tumor cell lines, HL-60 (leukemia carcinoma), MCF-7 (breast carcinoma), and Hep-G2 (hepatic carcinoma), with half maximal inhibitory concentration (IC₅₀) values of 12–48 μM.     

Five novel prenylated xanthones from Resina Garciniae

Fourteen prenylated xanthone derivatives were isolated from gamboge, the dry latex of Garcinia hanburyi, and their structures were elucidated by a detailed spectroscopic analysis. Five of them, isogambogenic acid (1), desoxymorellinin (2), 10-methoxygambogenic acid (3), 10-methoxygambogic acid (4) and 10-ethoxy gambogic acid (5), are new compounds. All of them showed potent cytotoxicity against HL-60, SMMC-7721 and BGC-83 cells.     

Triterpenes from Astilbe chinensis

Six new triterpenes, 3β,6β-dihydroxyurs-12-en-27-oic acid (1), 3β,6β,24-trihydroxyurs-12-en-27-oic acid (2), 3β,6β,7α-trihydroxyurs-12-en-27-oic acid (3), 3β-acetoxy-6β-hydroxyurs-12-en-27-oic acid (4), 3β,6β,24-trihydroxyolean-12-en-27-oic acid (5), and 3β,6β,7α-trihydroxyolean-12-en-27-oic acid (6), were isolated from the rhizomes of Astilbe chinensis. Their structures were elucidated on the basis of 1D- and 2D-NMR analyses and HR-MS experiments. The isolated compounds exhibited significant cytotoxic activities against the SK-N-SH and HL-60 cell lines.     

One pair of new cyclopentaisochromenone enantiomer from Alternaria sp. TNXY-P-1 and their cytotoxic activity

One pair of new cyclopentaisochromenone derivatives, (+)-(S)-6-hydroxy-1,8-dimethoxy-3a-methyl-3,3a-dihydrocyclopenta[c]isochromene-2,5-dione (1a) and (-)-(R)-6-hydroxy-1,8-dimethoxy-3a-methyl-3,3a-dihydrocyclopenta[c]isochromene-2,5-dione (1b), together with seven known analog 2?8, were isolated from a rice solid culture of the endophytic fungus Alternaria sp. TNXY-P-1, obtained from fresh leaf of Arisaema heterophyllum. Their structures were elucidated on the basis of detailed 1D, 2D NMR, and HRESIMS analysis. Among them, compounds 1a and 1b were enantiomers separated from 1 by chiral HPLC. The absolute configurations of 1a and 1b were assigned by quantum chemical calculations of the electronic circular dichroic spectra. All isolated compounds were evaluated for cytotoxic activities. Interestingly, enantiomers (+)-1a and (?)-1b showed distinct selective antitumor activities against HL-60 cell lines with IC₅₀ values of >200, 75.3 μM, respectively.