吸铜海洋真菌Fusarium sp.#ZZF51的代谢产物二（5-丁基-2-吡啶甲酸）合铜络合物的研究

A copper coordination compound ZZF51(A) named bis(5‐butyl‐2‐pyridinecarboxylato‐N1,O2)‐copper, the first time found in the nature, was isolated from a marine endophytic fungus Fusarium sp. ZZF51 from the South China Sea coast. Its structure was elucidated using spectroscopic methods and single crystal X‐ray diffraction analysis. The antimicrobial cytotoxicity experiments exhibited that ZZF51(A) had mutagenicity activities against four aerobic reference strains Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Salmonella enteritidis with respective MIC values of 12.5, 25, 12.5, and 50 µg/mL. The anti‐cancer tests showed that the compound had strong inhibitory activities against three human cancer lines KB, KBv200, and HepG2 with IC₅₀ values of 3.54, 3.68 and 25.12 µg/mL respectively. In the course of investigating the source of ZZF51(A) in biomass, it was found that the output of ZZF51(A) was largely influenced by the amount of CuCl₂ in the liquid medium, and the fungus (No. ZZF51) had two notable characteristics:endurance of high concentration Cu(II) ions and biosorption of Cu(II) ions.     

Cytotoxic Isoprenylated Flavonoids from the Roots of Sophora flavescens

Three new flavonoids, which are isoprenylated by fused 2,2‐dimethyl‐3,4‐dihydro‐2H‐pyran moieties, were isolated from the roots of Sophora flavescens and named flavenochromanes A–C ( 1 – 3 ). Their structures were elucidated by spectroscopic methods, including 2D‐NMR techniques. Flavenochromane C ( 3 ) showed strong cytotoxic activity against A549 (lung carcinoma), 1A9 (ovarian carcinoma), KB (epidermoid carcinoma of the nasopharynx), and KB‐Vin (drug‐resistant variant KB) cell lines with IC₅₀ values ≤1.7 μM , and significant activity against the MCF‐7 (breast adenocarcinoma) cell line with an IC₅₀ value of 3.6 μM . Flavenochromane B ( 2 ) displayed slightly lower inhibitory effects (IC₅₀ 3.2–6.9 μM ) as compared with 3 .     

Non‐Flat Bisbenzylisoquinoline Alkaloid Fangchinoline As a Class of Potent G‐Quadruplex Stabilizer with Anti‐cancer Activity

Compounds selectively binding and stabilizing G‐quadruplex structures could inhibit the telomerase or down‐ regulate the oncogenes and may act as anti‐cancer drugs. An alkaloid with non‐flat structure, fangchinoline, showed to strongly stabilize the intermolecular and intramolecular parallel stranded G‐quadruplex structure, increasing melting temperature by 20 and 23°C, respectively. The binding mode was investigated by using NMR and molecular modelling methods. Four human cell lines (HL‐60, BGC‐823, Bel‐7402 and KB) were taken to test the anti‐proliferation effects of fangchinoline and the IC₅₀ values were ranged from 16 to 32 µmol/L. These results showed that the fangchinoline or related moiety derivatives may represent a class of telomere‐targeted agents as potential anti‐cancer drugs.     

N‐(Substituted benzyl)‐3,5‐bis(benzylidene)‐4‐piperidones: Synthesis and Preliminary Anti‐leukemia Activity (I)

A series of novel N‐(substituted benzyl)‐3,5‐bis(benzylidene)‐4‐piperidones 5a – 5o were synthesized with substituted benzylamines as raw materials via a series of Michael addition, Dieckmann condensation, hydrolysis decarboxylation and aldol condensation. The structures were confirmed by ¹H NMR, IR, MS techniques and elemental analysis. Assay‐based antiproliferative activity study using leukemic cell lines K562 revealed that most of the title compounds have high effectiveness in inhibiting leukemia K562 cells proliferation, among which the compounds 5g (IC₅₀=7.81 µg·mL⁻¹), 5k (IC₅₀=6.35 µg·mL⁻¹), 5l (IC₅₀=7.20 µg·mL⁻¹), and 5o (IC₅₀=5.79 µg·mL⁻¹) have better inhibition activities than standard 5‐fluorouracil (IC₅₀=8.56 µg·mL⁻¹).     

Synthesis and Anti‐tumor Evaluation of Novel C‐37 Modified Derivatives of Gambogic Acid

Gambogic acid (GA, 1 ), the most prominent representative of Garcinia natural products, has been reported to be a promising anti‐tumor agent. In order to further explore the structure‐activity relationship of GA and discover novel GA derivatives as anti‐tumor agents, 17 novel C‐37 modified derivatives of GA were synthesized and evaluated for their in vitro anti‐tumor activities against A549, HCT‐116, BGC‐823, HepG2 and MCF‐7 cancer cell lines. Among them, 11 compounds were found to be more potent than GA against some cancer cell lines. Notably, compound 8 was almost 5–10 folds more active than GA against A549 and BGC‐823 cell lines with the IC₅₀ values of 0.12 µmol·L^?1 and 0.57 µmol·L^?1, respectively. Chemical modification at C‐37 position of GA by introducing of hydrophilic amines could lead to increased activity and improved drug‐like properties. These findings will enhance our understanding of the structure‐activity relationship (SAR) of GA and lead to the discovery of novel GA derivatives as potential anti‐tumor agents.     

Structure elucidation and NMR assignments for two xanthone derivatives from a mangrove endophytic fungus (No. ZH19)

The structure elucidations and complete ¹H and ¹³C NMR assignments are reported for two new xanthone derivatives: 1,7‐dihydroxy‐2‐methoxy‐3‐(3‐methylbut‐2‐enyl)‐9H‐xanthen‐9‐one (1) and 1‐hydroxy‐4,7‐dimethoxy‐6‐(3‐oxobutyl)‐9H‐xanthen‐9‐one (2). Both of these secondary metabolites were isolated from the fermentation medium of a mangrove endophytic fungus (No. ZH19). High‐resolution electron impact mass spectrometry (HREIMS), Fourier transform infrared (FT‐IR) absorption spectrometry, and NMR experiments including gCOSY, gHMQC, and gHMBC were used for the determination of the structures and NMR spectral assignments. Preliminary pharmacological test showed that compounds (1) and (2) inhibited KB cells with IC₅₀ values of 20 and 35 µmol/ml, and KB_V200 cells with IC₅₀ values of 30 and 41 µmol/ml, respectively. Copyright © 2009 John Wiley & Sons, Ltd.     

First carbonyl metallo immunoassay in the environmental area: application to the herbicide chlortoluron

We report a new, non‐isotopic, immunoassay (CMIA) for chlortoluron, a pesticide of the phenylurea family. The novel feature of this assay is the use of metal carbonyl complexes as tracers and Fourier‐transform infrared (FT‐IR) spectroscopy as the detection method. We describe the synthesis of three tracers, derivatives of chlortoluron with an attached cyclopentadienyl manganese tricarbonyl moiety. Quantitative analysis of these tracers, by FT‐IR spectroscopy was performed by simple measurement of the absorbance peak at 2033 cm^?1, characteristic of the ν_CO of the metal‐carbonyl unit. Immunoassays were carried out using the IgG fraction of rabbit antiserum. Standard curves obtained by CMIA for the three tracers showed the feasibility of this technique for chlortoluron assay. However, the IC₅₀ and IC₉₀ values obtained with the three tracers varied widely, with the long‐chain tracer 12 giving the most sensitive assay for chlortoluron, with an IC₅₀ value of 50 pmol (21 µg l^?1) and an IC₉₀ of 6.5 pmol (2.7 µg l^?1). Copyright © 2002 John Wiley & Sons, Ltd.     

Evaluation of newly synthesized derivatives of bis(hydrazine‐1‐carbothioamide) and their metal complexes synthesized in bulk and nano size as potent anticancer agents

A series of new metal complexes were synthesized in both bulk and nano size using green methods, starting with the reaction of (E)‐N′‐[(E)‐2‐bromobenzylidene]‐4‐oxo‐4‐(piperidin‐1‐yl)but‐2‐enehydrazide with thiosemicarbazide and different metal halides such as CuI·2H₂O, CuCl₂·2H₂O, CoCl₂·2H₂O, and ZnCl₂·2H₂O, and metal nitrate such as Ga(NO₃)₃·2H₂O. Structures of these metal complexes were confirmed using different spectroscopic methods, elemental analysis, electronic spectra, and microanalytical methods (scanning electron microscopy and transmission electron microscopy) for nano complexes. The distorted octahedral geometry for all complexes was suggested based on magnetic moments and electronic spectral studies. The cytotoxic activity of the compounds was investigated against human hepatocellular carcinoma (HepG2) and human colorectal carcinoma (HCT‐116) cell lines. Most tested compounds had higher inhibitory activity than the standard vinblastine drug. Interestingly, the nano‐sized Ga(III) complex 11 was the most potent compound against the two tested cell lines, with 50% inhibitory concentration (IC₅₀) of 2.56 μg/mL for HepG2, compared with the reference drug vinblastine (IC₅₀ 15.6 μg/mL), and IC₅₀ 4.64 μg/mL for HCT‐116, compared with the standard (IC₅₀ 13.9 μg/mL). The bioassay results helped us identify new potent and selective anticancer agents.     

Study on the Synthesis and Bioactivity of Novel Mahkoside A Derivatives

Abstract

A series of novel Mahkoside A derivatives was synthesized, and their in vitro cytotoxic activities were evaluated against the human cancer cell line Ec‐9706. A Preliminary structure–activity relationship study showed compounds 7 and 8 have obvious cytotoxic activities (IC₅₀: 30.0 and 12.5 µg · mL^?1, respectively).     

Synthesis and Anti‐cancer Activity of 1,3,4‐Thiadiazole and 1,3‐Thiazole Derivatives Having 1,3,4‐Oxadiazole Moiety

Reaction of 1,3,4‐oxadiazolyl‐phenylthiourea 3 with hydrazonoyl halides gave the corresponding 1,3,4‐oxadiazolylimino‐1,3,4‐thiadiazoles. Also, treatment of 3 with ethyl chloroacetate and α‐haloketones afforded the corresponding thiazolidinone and thiazole derivatives, respectively. The structures of the synthesized products were confirmed by spectral data. Ten compounds were evaluated for their anti‐cancer activity against the colon carcinoma cell line (HCT‐116). The results revealed that 1,3,4‐thiadiazole derivatives 13d and 19c (IC₅₀ = 0.73 and 0.86 µg/mL, respectively) have promising antitumor activity against colon carcinoma (HCT‐116), and most of the tested compounds showed moderate anti‐cancer activity.     

Investigation of the Effect of Four Organic Acids in Radix Isatidis on E. coli Growth by Microcalorimetry

The inhibitory effects of four organic acids (OAs) in Radix Isatidis, a traditional Chinese medicinal herb, on Escherichia coli (E. coli) growth were investigated by microcalorimetry. The power‐time curves of E. coli growth with and without OAs were acquired, meanwhile the extent and duration of inhibitory effects on the metabolism were evaluated by growth rate constants (k₁, k₂), half inhibitory ratio (IC₅₀), maximum heat output (P_max) and peak time (t_p). The values of k₁ and k₂ of E. coli growth in the presence of the four OAs decreased with the increasing concentrations of OAs. Moreover, P_max was reduced and the value of t_p increased with increasing concentrations of the four drugs. The sequence of anti‐microbial activity of the four OAs was: syringic acid>2‐amino‐benzoic acid>salicylic acid>benzoic acid. IC₅₀ of the four OAs was respectively 56 µg/mL for syringic acid, 75 µg/mL for 2‐amino‐benzoic acid, 86 µg/mL for salicylic acid and 224 µg/mL for benzoic acid. The existence of the functional groups on phenyl ring improves the anti‐microbial activity compared to benzoic acid. The functional groups methoxyl at C(3) and C(5) improve anti‐microbial activity more strongly than the other functional groups, and the functional group amino at C(2) improve anti‐microbial activity more strongly than hydroxyl at C(2) on phenyl ring.     

Cytotoxic activity of two polyaspartamide‐ based monoamineplatinum(II) conjugates against the HeLa cancer cell line

In this screening study in vitro, two polymer‐conjugated, square‐planar platinum(II) complexes bound to the carrier via a single primary amine ligand were tested for antineoplastic activity against the HeLa human cervical epithelioid carcinoma cell line. In the first of these conjugates, 1‐Pt , the spacer connecting the metal complex with the carrier backbone is a short oligo(ethylene oxide) segment, whereas a long poly(ethylene oxide) chain represents the spacer unit in the second conjugate, 2‐Pt . IC₅₀ data, expressed as conjugate concentration at 50% cell growth inhibition, are 48 µg Pt ml⁻¹ for 1‐Pt and 120 µg Pt ml⁻¹ (estimated) for 2‐Pt , the long tether in the latter conjugate presumably causing retarded enzymic release and lysosomal membrane crossing of the monomeric complex. The IC₅₀ value of 1‐Pt is close to that (44 µg Pt ml⁻¹) of a similar conjugate of an earlier investigation, 3‐Pt , in which the metal is chelated by two carrier‐attached, cis‐oriented amino groups in conformance with the ligand arrangement in cisplatin. It thus appears that, in the carrier‐bound state, both monoamine‐ and cis‐diamine‐coordinated platinum(II) complexes of suitable structures may well show similar biological performance patterns. Copyright­© 1999 John Wiley & Sons, Ltd.     

Synthesis,structure and in vitro cytotoxicity of platinum(II) complexes containing eugenol and a quinolin‐8‐ol‐derived chelator

The synthesis of potassium (η²‐4‐allyl‐2‐methoxyphenol)trichloridoplatinate(II), K[PtCl₃(C₁₀H₁₂O₂)], ( 1 ), starting from Zeise's salt and Ocimum sanctum L. oil has been optimized. Starting from ( 1 ), three new platinum(II) complexes, namely (η²‐4‐allyl‐2‐methoxyphenol)chlorido(2‐methylquinolin‐8‐olato‐κ²N ,O )platinum(II), ( 2 ), (η²‐4‐allyl‐2‐methoxyphenol)chlorido(5‐nitroquinolin‐8‐olato‐κ²N ,O )platinum(II), ( 3 ), and (η²‐4‐allyl‐2‐methoxyphenol)chlorido(5,7‐dichloroquinolin‐8‐olato‐κ²N ,O )platinum(II), [Pt(C₉H₄Cl₂NO)Cl(C₁₀H₁₂O₂)], ( 4 ), containing eugenol and a quinolin‐8‐ol derivative (R‐OQ), have been synthesized and characterized by elemental analyses, MS, IR, ¹H NMR and NOESY spectra. For ( 1 ) and ( 4 ), single‐crystal X‐ray diffraction studies were also carried out. Complexes ( 2 )–( 4 ) show good inhibiting abilities on three human cancer cell lines, i.e. KB, Hep‐G2 and LU, with IC₅₀ values of 1.42–17.8 µM . Complex ( 3 ) gives an impressively high activity against KB, Hep‐G2, LU and MCF‐7, with IC₅₀ values of 1.42–4.91 µM , which are much lower than those of cisplatin and some other platinum(II) complexes.     

Study on the New Fluorescence Immunoassays for the 2,4,6‐Trichlorophenol in the Environmental Water

Abstract

This study reported that the hapten of 2,4,6‐trichlorophenol (2,4,6‐TCP) was synthesized by using 2,4,6‐TCP reacted with chloroactic acid in alkaline solution. The hapten was conjugated to bovine serum albumin (BSA) with the modified active ester method to form artificial immune antigen. The anti‐TCP polyclonal antibodies were obtained by using the artificial immuneantigen (TCP‐BSA) to immunize the rabbits. Using the purified antiserum of highest specificity, an antibody‐coated fluoroimmunoassay was developed that shows an IC₅₀ of 4.8 µg/L with a limit of detection of 0.25 µg/L. The antibody showed negligible cross‐reactivity with other phenols, which makes their assays suitable for the selective detection of 2,4,6‐TCP. It shows a good accuracy and suitability to analyze, 2,4,6‐TCP in environmental water.     

Synthesis and Cytotoxicity of Some Thieno[2,3‐d]pyrimidine Derivatives

A series of compounds 5‐amino‐2‐ethylmercapto‐4‐phenyl‐6‐subistitutedthieno[2,3‐d]pyrimidines ( 8a–d ), 4‐chloro‐7‐ethylmercapto‐9‐phenylpyrimido[5′,4′:4,5]thieno[3,2‐d]triazine ( 9 ), and 2‐ethylmercapto‐8‐oxo‐4‐phenyl‐7‐(4‐chlorophenyl)pyrimido [4′,5′:4,5]thieno[2,3‐d]pyrimidine ( 10 ) were synthesized and their structures were confirmed by ¹H NMR , ¹³C NMR, and MS . All compounds were evaluated for their IC₅₀ values against three cancer cell lines (MCF ‐7, HUH ‐7 and BHK ) and WISH cells. The IC₅₀ of compound ( 8d ) was calculated for each cell line. Interestingly, the IC₅₀ for the normal human amnion WISH cell line was much higher (723 µg/mL) than those found for the tumor cell lines BHK (17 µg/mL), HUH ‐7 (5.8 µg/mL), and MCF ‐7 (8.3 µg/mL). The proliferation inhibition of normal (WISH ) and tumor (BHK , HUH ‐7, and MCF ‐7) cells by compound ( 8d ) was investigated using MTT assay, and the IC₅₀ was calculated after 48 h of treatment for each cell line.     

Bioguided Isolation and Antiproliferative Activity of Constituents from Smilax korthalsii A.D.C. Leaves

Ethyl acetate extract of Smilax korthalsii A.D.C. leaves exhibited antiproliferative activity on leukaemia carcinoma K562, hepatic liver cancer cells WRL and colorectal carcinoma with IC₅₀ of 125.20, 46.10 and 160.00 μM respectively. Isolation of the bioactive ethyl acetate extract of Smilax korthalsii A.D.C. leaves gave eight compounds; 3β‐hydroxyspirost‐5‐ene (diosgenin), 1 , β‐sitosterol, 2 , lup‐5,11,20‐trien‐23‐ol, 3 , uneicos‐9‐enoic acid, 4 , ethylheptadecan‐17‐oic‐9‐enoate, 5 , cis‐octadec‐9‐enoic acid, 6 , hexadec9‐enoic acid, 7 and 11‐methyltridec‐12‐en‐1‐ol, 8 . The isolated compounds were tested against four human cancer cell lines: leukaemia carcinoma, K‐562; hepatic liver cancer cells, WRL; colorectal carcinoma, COLO; and breast carcinoma, MCF‐7 using the MTT assay. Diosgenin 1 exhibited significant antiproliferative activity against all four cell lines (IC₅₀; K562=6.25, WRL=14.34, COLO=38.00, MCF‐7=12.40 μM), while compounds 3, 6 and 7 inhibited the growth of K‐562 at 20, 50 and 100 μM concentrations with IC₅₀ of 90.20, 75.92 and 50.72 μM respectively. Other isolated compounds also showed cytotoxic properties against K‐562, WRL and COLO, but showed low inhibition of MCF‐7.     

Anticancer metallopharmaceutical agents based on mixed‐ligand palladium(II) complexes with dithiocarbamates and tertiary organophosphine ligands

Mixed‐ligand palladium(II) complexes of the type [(DT)Pd(PR₃)Cl], where DT = diethyldithiocarbamate (1), dibutyldithiocarbamate (2,3), dipropyldithiocarbamate (4,5), bis(2‐methoxyethyl)dithiocarbamate; PR₃ = benzyldiphenylphosphine (1,4), diphenyl‐o‐tolylphosphine (2), diphenyl‐t‐butylphosphine (3), P‐chlorodiphenylphosphine (5) and triphenylphosphine (6), have been synthesized and characterized by elemental analyses and FT‐IR, Raman and multinuclear NMR spectroscopy. The structures of compounds 1 and 2 were determined by single‐crystal X‐ray diffraction (XRD) measurements and these analyses showed that the complexes have pseudo square‐planar geometry around the Pd(II) and that the dithiocarbamate ligand is bound in a bidentate fashion, while the remaining two positions are occupied by a tertiary organophosphine and a chloride ligand. The anticancer studies showed that the Pd(II) complexes are highly active against cisplatin‐resistant DU145 human prostate carcinoma (HTB‐81) cells with the highest activity shown by compound 6 (IC₅₀ = 2.12 µm ). The redox behavior and ds‐DNA‐denaturing ability of the complexes were studied by cyclic voltammetry and two reduction and one oxidation waves were observed. The decrease in the reduction peak currents illustrated the consumption of the mixed‐ligand drug by the DNA molecule. Copyright © 2013 John Wiley & Sons, Ltd.     

Design,synthesis, in vitro and in silico studies of naproxen derivatives as dual lipoxygenase and α-glucosidase inhibitors

A series of 28 novel naproxen derivatives (4a-f, 5a-f, 6a-d, 7a-f, and 8a-f) have been designed, synthesized, and characterized. The synthesized derivatives were assessed as dual inhibitors for 15-lipoxygenase (LOX) and α-glucosidase enzymes and checked for cytotoxicity and ADME studies. The inhibitory potential of naproxen derivatives for 15- LOX was checked through two different methods, the UV absorbance method and the Chemiluminescence method. The biological activities result revealed that through the UV absorbance method, compound 4f (IC₅₀ 21.31 ± 0.32 µM) was found potent among the series followed by compounds 4e (IC₅₀ 36.53 ± 0.51 µM) and 4d (IC₅₀ 49.62 ± 0.12 µM) against standard drug baicalein (IC₅₀ 22.46 ± 1.32 µM) and quercetin (IC₅₀ 2.34 ± 0.35 µM), while through chemiluminescence method tested compounds showed significant 15-LOX inhibition at the range of IC₅₀ 1.13 ± 0.62 µM ?123.47 ± 0.37 µM. Among these compounds, 4e (IC₅₀ 1.13 ± 0.62 µM), 5b (IC₅₀ 1.19 ± 0.43 µM), 8c (IC₅₀ 1.23 ± 0.35 µM) were found most potent inhibitors against quercetin (IC₅₀ 4.86 ± 0.14 µM), and baicalein (IC₅₀ 2.24 ± 0.13 µM). The chemiluminescence method was found more sensitive than the UV method to identify 15-LOX inhibitors. Interestingly all synthesized compounds showed significant α-glucosidase inhibitory activity (IC₅₀ 1.0 ± 1.13 µM ? 367.2 ± 1.23 µM) even better than the standard drug acarbose (IC₅₀ 375.82 ± 1.76 µM), while compound 6c (IC₅₀ 1.0 ± 1.13 µM) and 7c (IC₅₀ 1.1 ± 1.17 µM) were found most potent compounds among the series even many folds better than the standard drug. The cell viability results showed that all compounds were less toxic, maintained cellular viability at the range of 99.8 ± 1.3% to 63.7 ± 1.5%. ADME and molecular docking studies supported drug-likeness and binding interactions of compounds with the targeted enzymes.     

Total Synthesis,Absolute Configuration,and Biological Activity of Xyloallenoide A

The novel natural product xyloallenoide A, isolated from the marine mangrove endophytic fungus from the South China Sea, and its diastereoisomer xyloallenoide A1, which contain N‐methyl‐substituted amino acids, were synthesized. The absolute configurations of the amino acid units of xyloallenoide A were finally confirmed to be L ‐Lys, Me‐D ‐Val, and Me‐L ‐Ala. This report represents a practical and attractive alternative for the synthesis of N‐methyl‐substituted cyclotripeptides. In the preliminary bioassay, synthetic xyloallenoide A showed marginal activities against KB (IC₅₀=9.6 μM ) and KBv200 cells (IC₅₀=10.3 μM ), and xyloallenoide A1 was inactive against KB and KBv200 cells.