Synthesis and cytotoxicity of novel steroidal C-20 oxime ester derivatives from 16-DPA

A series of novel steroidal C-20 oxime ester derivatives were prepared from 16-DPA, and their structures were characterized by IR, 1D-NMR and ESI-MS methods. The compounds were tested against NB4, PC-3 and HeLa cancer cells in vitro, five of which showed potent cytotoxicity. Preliminary results indicated that structure modification of C-20 oxime ester may have potential cytotoxicity.     

Six New Sesquiterpenes from Eupatorium lindleyanum

The six new germacrane‐type sesquiterpenoid lactones 1 – 6 were isolated from the CHCl₃ extract of Eupatorium lindleyanum DC. The structures of these compounds were determined by spectroscopic analyses, including interpretation of 1D‐ and 2D‐NMR spectra. Compounds 1 – 6 were tested for cytotoxicity against NB4 and K562 leukemia cell lines, showing that 2 and 5 possess potent cytotoxicity (Table 3).     

Design, synthesis and cytotoxicity of novel podophyllotoxin derivatives

A series of novel podophyllotoxin derivatives were designed using association strategy and synthesized by coupling either podophyllotoxin (1) or 4beta-amino podophyllotoxin (3) with substituted indol-3-yl-glyoxyl chlorides. Their structures were identified using spectroscopic techniques. These novel derivatives have been evaluated for cytotoxicity in vitro against four human cancer cell lines with comparison to the parent compounds 1, 3 and indibulin (2). Some of the compounds (7a, 7c) showed comparable cytotoxicity to that of podophyllotoxin.     

Four New Nortriterpenoids from Schisandra lancifolia

Four new highly oxygenated nortriterpenoids, lancifodilactones O–R ( 1 – 4 ), together with six known ones, i.e., 5 – 10 , were isolated from the leaves and stems of Schisandra lancifolia. Their structures were elucidated by spectroscopic analyses, including 1D‐ and 2D‐NMR experiments and mass spectrometry. Compounds 1 – 3 were evaluated for their cytotoxicity against NB4, A549, SHSY5Y, PC‐3, and MCF‐7 cell lines. No compounds exhibited significant cytotoxicity, the IC₅₀ values being above 50 μM .     

二芳醚基哌嗪类衍生物的合成及细胞毒活性研究

根据拼合原理, 设计并合成了21个未见报道的新的二芳醚基哌嗪类衍生物, 其结构用1H NMR, ESI-MS, HRMS进行了确证, 初步生物活性测定实验证明部分目标化合物具有良好的细胞毒活性. 化合物4i分别对人食管癌(Eca109)细胞株和人鼻咽癌(CNE)细胞株的IC50为7.13和4.54 μmol•L－1, 与对照品顺铂(DDP)相近. 化合物5d对人鼻咽癌细胞株也表现较好的活性, 其IC50为8.49 μmol•L－1.     

Design and synthesis of novel cytotoxic podophyllotoxin derivatives

<正>In order to investigate the effect of different C4 linkage moieties on the cytotoxicity of podophyllotoxin derivatives,novel 4-Nand 4-C-substituted 4'-O-demethylepipodophyllotoxin derivatives were designed and synthesized.All the compounds were tested against A549 and MCF-7 tumor cells in vitro,and six compounds showed significant cytotoxicity.The most active compound 9f was superior to GL-331,and exhibited potent cytotoxicity with IC_(50) value at 10~(-7) mol/L level.     

Synthesis,Anti‐Microbial,and Cytotoxic Activities Evaluation of Some New Pyrido[2,3‐d]Pyrimidines

Novel pyridine derivatives 1d and 7 , pyrido[2,3‐d]pyrimidine derivatives 2a , 2b , 2c , 2d , 3a , 3b , 3c , 3d , 4a , 4b , 4c , 4d , 5a , 5b , 5c , 5d , 6a , 6b , 6c , 6d , 8a , 8b , and 9a , 9b were synthesized and screened for their anti‐microbial and cytotoxic activities. Compounds 2b , 2c , 3b , 3c , 5b , 5c , 6b , 6c , and 7 showed excellent anti‐microbial activities against all the tested bacteria and fungi compared to the reference drugs. Furthermore, they exhibited high safety profile in cytotoxicity test except 2c and 3c . The structures of the newly synthesized compounds were confirmed by spectral data and elemental analysis.     

Two new isoaurones derivatives from Callistephus chinensis flower

Two new isoaurones derivatives were obtained from Callistephus chinensis flower. Their structures were elucidated on the basis of extensive spectroscopic analyses. Both of the new compounds were evaluated cytotoxic activity. Phytochemical investigation of Callistephus chinensis flower led to the isolation of two new isoaurones derivatives (Z)-4′,4,10-trihydroxy-siamaurone (1) and (E)-4′,4,10-trihydroxy-siamaurone (2). The structures of these new compounds were identified by the interpretation of spectroscopic data (mainly 1D and 2D NMR) and by comparison with data reported in the literature. Both of the new compounds were evaluated for their cytotoxicity.     

Synthesis of New 4,5-Dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-amine–Derived Ureas and Their Anticancer Activity

A new series of 1,2,4-triazolo[4,3-a]-quinoline derivatives were designed and synthesized to meet the structural requirements essential for anticancer activity. N-1-(5-Methylisoxazol-4-yl/4-fluoro-2,3-dihydro-1H-inden-1-yl/aryl)-N’-3-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl) urea derivatives were accomplished in good yields by the reaction of 4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-amine with 3-(3-chloro-5-fluoro-2-methoxyphenyl)-5-methyl-isoxazole-4-carboxylic acid, 4-fluoro-2,3-dihydro-1H-indene-1-carboxylic acid, and various simple aromatic carboxylic acids in the presence of diphenyl phosphoryl azide (DPPA). All the newly synthesized title compounds were characterized by elemental and spectral data. Furthermore, anticancer activity was screened for the title compounds (12a–j) in vitro against human neuroblastoma cell lines (SK N SH) and human colon carcinoma cell lines (COLO 205) by using the MTT cell viability method. A few of them (12a and 12b) possess significant cytotoxicity, and some other compounds 12d-f and 12j displayed moderate cytotoxicity against both cell lines.     

4-Azatricyclo[5.2.2.02,6]undecane-3,5,8-triones as potential pharmacological agents

A series of twenty six arylpiperazine and aminoalkanol derivatives of 4-azatricyclo[5.2.2.0(2,6)]undecane-3,5,8-trione have been prepared. The synthesized compounds were evaluated for their cytotoxicity and anti-HIV-1 activity in MT-4 cells.     

20 （S） -20-O- Camptothecin β-Aminopropionate： Novel Synthesis and Antitumor Activity in vitro

IntroductionCamptothecin(CPT,1, Scheme 1), a pentacyclicalkaloid isolated from theCamptotheca acuminatebyWallet al. in 1966, shows a broad-spectrum antitumoractivity[1]. However, because of its lowwater solubilityand high toxicity, its clinical applicatio…     

Synthesis and characterization of a novel functionalized azanonaborane cluster for boron neutron capture therapy

The reactivity of an azanonaborane cluster containing free amino groups {H2N(CH2)4H2NB8H11NH(CH2)4NH2} towards ketones and aldehydes is investigated. In a one step reaction, the reductive amination of some ketones and aldehydes (namely acetone, benzaldehyde, 3-hydroxybenzaldehyde, 4-hydroxybenzaldehyde, 4-nitrobenzaldehyde, 4-acetoxybenzaldehyde, and 4-acetamidobenzaldehyde) with an azanonaborane cluster in the presence of H3BNH2(CH2)4NH2 gives monoalkylamino derivatives of the azanonaborane cluster {RHN(CH2)4H2NB8H11NH(CH2)4NHR} where (R =(Me)2CH-, C6H5CH2-, 3-OHC6H4CH2-, 4-OHC6H4CH2-, 4-NO2C6H4CH2-, 4-MeOCOC6H4CH2-, or 4-NH2COC6H4CH2-). The functionalized derivatives of the {B8N} cluster can be used in boron neutron capture therapy for tumors (BNCT). Similarly, the reductive amination of 5-(4"-formylphenyl)-10,15,20-triphenylporphyrin with the {B8N} cluster gave a porphyrin bearing azanonaborane cluster, while a porphyrin dimer linked by an azanonaborane moiety was obtained following the same method, starting with a 2:1 molar ratio of porphyrin:{B8N} cluster. 5,10,15,20-Tetraformylphenylporphyrin gave the chance to increase the percentage of boron in the resulting boronated porphyrin, which is considered an important factor for a BNCT delivery agent. With these compounds, the cell toxicity using V79 cells was carried out to determine whether these compounds would have favorable biological properties.     

Cytotoxicity of constituents from Mexican propolis against a panel of six different cancer cell lines

The cytotoxicity of 39 compounds, including eighteen flavonoids (flavanones, 1-10; flavones, 11-17; flavanol, 18), sixteen phenolic acid derivatives (aromatic acids, 19-24; aldehyde, 25; esters, 26-34) and five glycerides (35-39), isolated from Mexican propolis, were evaluated against a panel of six different cancer cell lines; murine colon 26-L5 carcinoma, murine B16-BL6 melanoma, murine Lewis lung carcinoma, human lung A549 adenocarcinoma, human cervix HeLa adenocarcinoma and human HT-1080 fibrosarcoma. A phenylpropanoid-substituted flavanol, (2R,3S)-8-[4-phenylprop-2-en-1-one]-4',7-dihydroxy-3',5-dimethoxyflavan-3-ol (18), showed the most potent cytotoxicity against A549 cells (IC50, 6.2 microM) and HT-1080 cells (IC50, 3.9 microM), stronger than those of the clinically used anticancer drug, 5-fluorouracil (IC50, 7.5 microM and 5.4 microM, respectively). Based on the observed results, the structure-activity relationships are discussed.     

DNA binding and biological activity of some platinum(II) intercalating compounds containing methyl-substituted 1,10-phenanthrolines

This study documents the first detailed investigation into the relationship between molecular structure and biological activity of platinum(II) complexes containing methylated derivatives of 1,10-phenanthroline (phen). A series of square planar platinum(II) compounds incorporating methylated derivatives of phen, 4-methyl-1,10-phenanthroline (4-Mephen), 5-methyl-1,10-phenanthroline (5-Mephen), 4,7-dimethyl-1,10-phenanthroline (4,7-Me2phen), 5,6-dimethyl-1,10-phenanthroline (5,6-Me2phen) and 3,4,7,8-tetramethyl-1,10-phenanthroline (3,4,7,8-Me4phen) were synthesised and the relationship between their structure and biological activity investigated. The biological activity of these compounds was quantified using the in vitro cytotoxicity assay against the L1210 Murine leukaemia cell line. Large variation in cytotoxicities with different methylation was observed. The 5- and 5,6-methylated derivatives of phen displayed a greater biological activity, with IC50 values of 2.8 +/- 0.8 microM and 1.5 +/- 0.3 microM respectively, compared with the phen compound, with an IC50 value of 9.7 +/- 0.3 microM, while all the others were inactive with IC50 values over 50 microM. Binding constants were determined using circular dichroism spectroscopy (CD) and induced circular dichroism (ICD). ICD was used to highlight any differences in the spectra. Viscometry studies and linear dichroism (LD) experiments indicate that the platinum(II) complexes intercalate although for [Pt(en)(4-Mephen)]Cl2 and [Pt(en)(4,7-Me2phen)]Cl2 this mode of binding appears to be concentration dependent. The binding of the platinum(II) complexes to the oligonucleotide d(GTCGAC)2 was studied using two-dimensional 1H NMR spectroscopy. The addition of each metal complex to the hexamer d(GTCGAC)2 produced upfield shifts of the metal complex resonances, characteristic of intercalation. Through the observation of NOE cross-peaks, two-dimensional NMR studies provided insight into the site and groove preferences of these compounds when binding to DNA.     

Potent cytotoxic rocaglamide derivatives from the fruits of Amoora cucullata

Two new rocaglamide derivatives, 1-O-formylrocagloic acid (1) and 3'-hydroxy rocagloic acid (2), together with five known compounds, rocaglaol (3), rocagloic acid (4), 3'-hydroxymethylrocaglate (5), 1-O-formylmethyl rocaglate (6), and methylrocaglate (7), were isolated from the fruits of Amoora cucullata. Their structures were elucidated by spectroscopic methods. Compounds 1-3, 6, and 7 exhibited potent cytotoxicity against KB, BC, and NCI-H187 cell lines, whereas 4 and 5 showed selective cytotoxicity against NCI-H187 cell line.     

Synthesis and pharmacological activity of urea and thiourea derivatives of 4-azatricyclo[5.2.2.0(2,6)]undec-8-ene-3,5-dione

A series of nineteen new thiourea and urea derivatives of 10-isopropyl-8-methyl-4-azatricyclo[5.2.2.0(2,6)]undec-8-ene-3,5-dione, 1-isopropyl-7-methyl-4-azatricyclo[5.2.2.0(2,6)]undec-8-ene-3,5-dione and 1,7,8,9,10-pentamethyl-4-azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione have been prepared and studied by (1)H-NMR. The compound k1a (1-(1,7,8,9,10-pentamethyl-3,5-dioxo-4-aza-tricyclo[5.2.1.0(2,6)]dec-8-en-4-yl)-3-phenyl-urea) was tested for pharmacological activity on animal central nervous system (CNS). The activities of synthesized compounds were evaluated for their cytotoxicity and anti-HIV-1 activity in MT-4 cells. Antimicrobial activity of the newly obtained derivatives was tested against some Gram-positive and Gram-negative bacteria and fungi of the Candida species.     

Melophlins P, Q, R, and S: four new tetramic acid derivatives, from two Palauan marine sponges of the genus Melophlus

Four new tetramic acid derivatives, named melophlins P, Q, R, and S (1-4), were isolated from two marine sponges of the genus Melophlus collected at Palau, together with seven known melophlins A, D, E, G, H, I, and O. The structures of the new compounds were elucidated on the basis of their spectral data. The absolute stereochemistries at the tetramic acid moieties of the new compounds were determined as 1 : 1 mixtures (racemic) by ESI-LC/MS analysis of derivatives obtained by oxidation and hydrolysis of the respective parent compounds. Melophlins P-S (1-4) showed cytotoxicity against the murine leukemia cell line L1210 with IC(50) values of 20.0, 10.5, 0.85, and 5.13 muM, respectively.     

Electron ionization mass spectra of 8‐aryl‐3,4‐dioxo‐2H,8H‐6,7‐dihydroimidazo[2,1‐c][1,2,4]triazines. Do they exhibit tautomerism in the gas phase?

The electron ionization mass spectra of the title compounds (1: a R = H, b 2-CH(3), c 4-CH(3), d 2,3-diMe, e 2-OCH(3), f 4-OCH(3), g 2-Cl, h 3-Cl, i 4-Cl, j 3,4-diCl) were recorded at 70 eV to determine the effects of substituents and the possible keto-enol tautomerism. The compounds showed several common fragment ions but also fragment ions which divided them into three classes, namely 1a-1d (parent compound and Me-substituted derivatives), 1e and 1f (MeO-substituted derivatives), and 1g-1j (Cl-substituted derivatives). The presence of the HOCN(+.) ion as well as the exponential dependence of its total ion current in the case of p- and also 3-Cl-substituted compounds (1a, c, f, h-j) on the Hammett sigma constants and the loss of CHO or one or two HOCN moieties can be somewhat easier explained by the presence of the enol form but as a whole the results support the predominance of the keto form, in parallel to the situation in solution.     

Synthesis of novel 1,3,4-oxadiazole derivatives and their nucleoside analogs with antioxidant and antitumor activities

A series of new (1,3,4-oxadiazol-2-yl)-1H-benzo[h]quinolin-4-one derivatives were synthesized, including glucose and xylose hydrazones that were obtained by the reaction of hydrazides with monosaccharides. Cyclization of the sugar hydrazones with acetic anhydride afforded substituted oxadiazoline derivatives. The newly synthesized compounds were evaluated for their antioxidant properties and cytotoxicity, and showed moderate to high activities.