Natural isothiocyanates of the genus Capparis as potential agonists of apoptosis and antitumor agents:Mechanisms and implications

In this editorial,we comment on a recent publication,which highlights the important findings from the study,including the antitumor and anti-inflammatory effects of isothiocyanates,their underlying mechanisms,and implications.Additionally,a related perspective is discussed.

Natural isothiocyanates of the genus Capparis as potential agonists of apoptosis and antitumor drugs

BACKGROUND Using gas chromatography-mass spectrometry(GC/MS)analysis,we examined the composition of volatile components present in the yellow and green fruits,seeds,and jam of the scrambling shrub Capparis cartilaginea(C.cartilaginea).These plant samples were collected from Kibbutz Yotvata in Israel.In all the tested samples,isothiocyanates were identified.Utilizing the PASS program,we ascertained the biological activity of these isothiocyanates present in the Capparis genus.The study results highlighted that all isothiocyanates could potentially act as apoptosis agonists,making them strong candidates for antitumor drugs.This information holds significant value for the fields of medicinal chemistry,pharmacology,and practical medicine.AIM To investigate the volatile components present in the yellow and green fruits,seeds,and jam of the C.cartilaginea shrub using GC/MS analysis,to detect isothiocyanates in all the analyzed plant samples,and to assess the biological activity of these isothiocyanates utilizing the PASS program.METHODS We utilized two primary methods to analyze the volatile compounds present in the yellow and green fruits,seeds,and jams of the C.cartilaginea,native to Israel.We identified biologically active isothiocyanates in these samples.Their anticipated biological activities were determined using the PASS program,with the most dominant activities being apoptosis agonist,anticarcinogenic,and antineoplastic specifically for genitourinary cancer.RESULTS Fruits,seeds,and jams containing isothiocyanates,which exhibit antineoplastic and anticarcinogenic activities,could be suggested for cancer prevention and management.Specific isothiocyanates,with therapeutic potential in this realm,could be recommended as potent anticancer agents in practical medicine following clinical trials.CONCLUSION The discovery that isothiocyanates exhibit potent antineoplastic and anticarcinogenic activities was unexpected.Additionally,certain isothiocyanates demonstrated antifungal,antiviral(specifically against arbovirus),and antiparasitic properties.

Studies on Rare Earth Complexes with Crown Ether (ⅩⅩⅣ)——Synthesis and Characterization of Complexes of Lanthanide Isothiocyanates with Dibenzo-30-crown-10

Introduction The study of metal complexes with the crown ether is a quite interesting research field, but the research has mainly focused on the metal complexes with some crown ethers with a relatively small cavity such as 12-crown-4, 15-crown-5 and 18- crown-6 as well as their derivatives. Crown ethers with a larger cavity contain more oxygen atoms, so they have the ability to form the complexes of a higher co-

Synthesis and Determination of Standard Molar Enthalpies of Formation for Complexes of Rare Earth Isothiocyanates with Glycine

Four solid complexes of rare earth isothiocyanates with glycine were synthesized. They were characterized by chemical analysis, elemental analysis, Infrared spectra, X-ray powder diffraction and TO-DSC analysis. Their chemical formulae were proved to be RE(NCS)2.Gly .H2O, where RE is La, Ce, Pr or Nd. The integral heats of solution of RE(NCS)3.3Gly. H2O in water, of RE(NCS)2. 7H2O in aqueous glycine solution and of glycine in water have been measured calorimetricaliy at 298. 15K. By means of a thermochemical cycle suggested in this paper, the standard molar enthalpies of formation for RE(NCS)2. 3Gly.H2O(c) were obtained and their lattice energies were calculated.

Perspective on dietary isothiocyanates in the prevention,development and treatment of cancer

Epidemiological evidence has highlighted the association of specific diets and a lower incidence of cancer.Foremost,the Mediterranean diet provides high levels of polyphenolics and a high consumption of healthier fats,e.g.,as from olive oil.In the Mediterranean region the consumption of vegetables is elevated providing a class of compounds,the isothiocyanates(ITCs)as found in the cabbage family.The ITCs have raised great interest for their health benefits over the past few decades.Some of the key ITC compounds,sulforaphane,phenethylisothiocyanate and benzyl isothiocyanate,have been studied in vitro and in vivo and the data support their promise for cancer chemoprevention,as anti-tumor agents,and for chemoprotection of normal tissues and organs.Along with other polyphenolic compounds in the diet,in general,they also possess key anti-inflammatory properties thus satisfying the criteria for compounds that could intervene in cancer initiation and progression.In this review we provide a larger overview of the advantages of including ITCs in the diet as food or as supplements and speculate on what could constitute a valuable therapeutic strategy for improving and sustaining good health and countering cancer disease in humans.

A Phelipanche ramosa KAI2 protein perceives strigolactones and isothiocyanates enzymatically

Phelipanche ramosa is an obligate root-parasitic weed that threatens major crops in central Europe.In order to germinate,it must perceive various structurally divergent host-exuded signals,including isothiocyanates(ITCs)and strigolactones(SLs).However,the receptors involved are still uncharacterized.Here,we identify five putative SL receptors in P.ramosa and show that PrKAI2d3 is involved in the stimulation of seed germination.We demonstrate the high plasticity of PrKAI2d3,which allows it to interact with different chemicals,including ITCs.The SL perception mechanism of PrKAI2d3 is similar to that of endogenous SLs in non-parasitic plants.We provide evidence that PrKAI2d3 enzymatic activity confers hypersensitivity to SLs.Additionally,we demonstrate that methylbutenolide-OH binds PrKAI2d3 and stimulates P.ramosa germination with bioactivity comparable to that of ITCs.This study demonstrates that P.ramosa has extended its signal perception system during evolution,a fact that should be considered for the development of specific and efficient biocontrol methods.

Efficient synthesis of thiohydantoin derivatives from amino acid esters and isothiocyanates in alkaline Al_2O_3

Various amino acid esters were reacted with different isothiocyanates in alkaline Al2O3 at room temperature for 1 h affording thiohydantoins in moderate to excellent yields.

Quantification of Total Glucosinolates and Isothiocyanates for Common Brassicaceous Vegetables Consumed in the US Market Using Cyclocondensation and Thiocyanate Ion Measurement Methods

Glucosinolates are a group of important sulfur and nitrogen containing plant secondary metabolites found in Brassicaceous vegetables that are associated with many health benefits.There is a growing interest in assessing dietary glucosinolates and their degradation products’isothiocyanates exposure to humans.Determination of glucosinolates in plants is a very challenging task.In this study,the total glucosinolates from 22 commonly consumed Brassicaceous vegetables in the US market were determined by employing 1,2-benzenedithiol cyclocondensation for the determination of isothiocyanates(ITCs)from non-indole glucosinolates and a colorimetric method for the determination of thiocyanate ion(SCN^(−))from indole glucosi-nolates.The total glucosinolates were determined from the sum of these two methods.In the 22 investigated vegetables,the highest level of total ITCs was found in horse radish(5189.0±544.8 nmol/g dry weight)and the highest level of total SCN^(−)level was found in brussel sprouts(1294.0±141.6 nmol/g dry weight).The total glucosinolates ranged from 18.6±3.2 to 2271.2±215.3 nmol/g dry weight.The total glucosinolate and ITC data are necessary for the USDA glucosinolates database and important for establishing the relationship of glucosinolates to human nutrition.

Diversity of glucosinolates among common Brassicaceae vegetables in China

Brassicaceae vegetables are an important traditional daily food in China and around the world, which provide nutrients and phytochemicals that are beneficial for human health. Among them, Brassica and Raphanus are widely cultivated and eaten, have been evolved and/or bred for special characteristics during the long history of cultivation. Epidemiological studies suggest that the health benefits of Brassicaceae vegetables are mainly associated with glucosinolates(GSLs) and their hydrolytic products. In this review, we discuss the diversity of common consumed Brassicaceae vegetables and their GSL composition in edible parts. We also discuss the diversity factors affecting GSL content, and the diversity roles and functions of GSL. The information in this review provides guidance for consumers to select vegetables with a high GSL content,optimum edible stages, suitable edible methods, and provides a theoretical basis for crop molecular breeding and market development of GSL products.

萝卜苗中异硫氰酸盐的动态变化及体外抗氧化活性

测定不同生长时期的6种萝卜苗(长春白萝卜苗、盛丰白萝卜苗、象牙白萝卜苗、德国特白萝卜苗、抚顺红萝卜苗及满堂红萝卜苗)正己烷提取物的总异硫氰酸盐和4-methylthio-3-butenyl isothiocyanate(MTBITC)含量,分别用FRAP法、ABTS法、抗超氧阴离子自由基(O-2·)和抗羟自由基(.OH)能力4种方法测定提取物的体外抗氧化性能。结果显示:萝卜苗中MTBITC含量占总异硫氰酸盐的80%以上;5～10d的萝卜苗中含有较高的MTBITC含量;同生长期的苗中,长春白萝卜苗、盛丰白萝卜苗、象牙白萝卜苗、德国特白萝卜苗的MTBITC含量比抚顺红萝卜苗和满堂红萝卜苗高。长春白萝卜苗、盛丰白萝卜苗、象牙白萝卜苗、德国特白萝卜苗4种萝卜苗的抗氧化性能与MTBITC含量呈正相关。而满堂红和抚顺红萝卜苗中MTBITC含量较低,但却表现出较强的抗氧化性能。

萝卜苗中异硫氰酸盐的提取工艺

以正己烷和二氯甲烷为溶剂,4-methylthio-3-butenyl isothiocyanate(MTBITC)和4-methylsulfinyl-3-butenyl isothiocyanate(Sulforaphene)的总量为提取效率研究萝卜苗中异硫氰酸盐的提取工艺。结果表明:提取萝卜苗中异硫氰酸盐的最佳工艺条件为自身酶解时间3～5min、液固比2:1(mL/g)、按正己烷-二氯甲烷-二氯甲烷的溶剂顺序各提取1次、提取时间3min/次。

Molecular mechanisms of chemopreventive phytochemicals against gastroenterological cancer development

Cancer is one of the leading causes of death worldwide.Commonly used cancer treatments,including chemotherapy and radiation therapy,often have side effects and a complete cure is sometimes impossible.Therefore,prevention,suppression,and/or delaying the onset of the disease are important.The onset of gastroenterological cancers is closely associated with an individual's lifestyle.Thus,changing lifestyle,specifically the consumption of fruits and vegetables,can help to protect against the development of gastroenterological cancers.In particular,naturally occurring bioactive compounds,including curcumin,resveratrol,isothiocyanates,(-)-epigallocatechin gallate and sulforaphane,are regarded as promising chemopreventive agents.Hence,regular consumption of these natural bioactive compounds found in foods can contribute to prevention,suppression,and/or delay of gastroenterological cancer development.In this review,we will summarize natural phytochemicals possessing potential antioxidant and/or anti-inflammatory and anti-carcinogenic activities,which are exerted by regulating or targeting specific molecules against gastroenterological cancers,including esophageal,gastric and colon cancers.

Antioxidant Activity of Isothiocyanate Extracts from Broccoli

Isothiocyanates(ITCs) extracts were prepared from fresh broccoli.Their antioxidant properties were evaluated by using the in vitro bioassays,including superoxide anion radical( 2 O·-) ,hydroxyl radical(HO·-) and 2,2-diphenyl-1-picrylhydracyl(DPPH·) radical-scavenging methods,lipid peroxidation assay,and reducing power assay.The ITCs extracts exhibited significant dose-dependent antioxidant activities(P<0.01) .Its antioxidant-stability was affected by temperature and storage condition,although it was more stable than vitamin C(Vc) .GC-MS iden-tified sulforaphane in the ITCs extracts.The antioxidant activity of sulforaphane was approximately one tenth to one fifth of that of Vc.Sulforaphane was experimented to be one of dominating contributors to antioxidant capacity of ITCs extracts.However,there was no direct antioxidant activity found for benzyl isothiocyanate(BITC) in vitro. Therefore,it could be concluded that the general group(-N=C=S) was not the essential part for the antioxidant activity of sulforaphane.It is suggested that the ITCs extracts from broccoli can be developed into a promising food additive for healthy food.

Sulforaphane as a Promising Natural Molecule for Cancer Prevention and Treatment

Tumorigenicity-inhibiting compounds have been identifled in our daily diet.For example,isothiocyanates(ITCs)found in cruciferous vegetables were reported to have potent cancer=prevention activities.The best characterized ITC is sulforaphane(SF).SF can simultaneously modulate multiple cellular targets involved in carcinogenesis,including(1)modulating carcinogen-metabolizing enzymes and blocking the action of mutagens;(2)inhibition of cell proliferation and induction of apoptosis;and(3)inhibition of neo-angiogenesis and metastasis.SF targets cancer stem cells through modulation of nuclear factor kappa B(NF-κB),Sonic hedgehog(SHH),epithelial-mesenchymal transition,and Wnt/βcatenin pathways.Conventional chemotherapy/SF combination was tested in several studies and resulted in favorable outcomes.With its favorable toxicological profile,SF is a promising agent in cancer prevention and/or therapy.In this article,we discuss the human metabolism of SF and its effects on cancer prevention,treatment,and targeting cancer stem cells,as well as providing a brief review of recent human clinical trials on SF.

Sulforaphene and sulforaphane in commonly consumed cruciferous plants contributed to antiproliferation in HCT116 colon cancer cells

Objective: To analyze two isothiocyanates(sulforaphene and sulforaphane) and their antiproliferative effect of 11 indigenous cruciferous vegetables.Methods: Phytoconstituents identification was conducted by high performance liquid chromatography and gas chromatography-mass spectrometer techniques. The antiproliferation was evaluated in colon cancer cell line HCT116 by MTT assay.Results: Isothiocyanate identification by high performance liquid chromatography showed that broccoli, cabbage, "Khi-Hood"(Raphanus sativus L. var. caudatus Alef) and Chinese radish contained isothiocyanates sulforaphane. Sulforaphene and sulforaphane in broccoli, cabbage and "Khi-Hood" were characterized by the gas chromatography-mass spectrometer analysis. Antiproliferation screening by MTT assay found that the potent plants which possessed IC_(50) below 50 mg/m L were cabbage and "Khi-Hood", while the others had low antiproliferation with IC_(50) higher than 50 mg/m L. Difference in antiproliferation was probably due to difference existed phytochemical constituents in each plant. "Khi-Hood" possessed the highest antiproliferation against HCT116 with the lowest IC_(50)at(9.42 ± 0.46) mg/m L. The IC_(50) of chemotherapeutic drug(mitomycin C)was(19.12 ± 1.00) mg/m L, while both melphalan and 5-fluorouracil possessed the IC_(50) value higher than 50 mg/m L.Conclusions: Commonly consumed cruciferous vegetables exerted varied antiproliferation and isothiocyanate contents. High isothiocyanate content in "Khi-Hood" was contributed to high antiproliferation. Among 11 plants studied, "Khi-Hood" could be an alternative chemopreventive diet.

Sulforaphene in Raphanus sativus L. var. caudatus Alef increased in late-bolting stage as well as anticancer activity

Objectives: To evaluate the concentration differences of sulforaphene and sulforaphane at various ages and in different parts of Raphanus sativus L. var. caudatus with respect to their potential cancer preventive effect on HCT116 colon cancer cells.Methods: FTIR–ATR and GC–MS were used to characterize the isothiocyanates in the plant extracts followed by HPLC for quantification. Antiproliferation and apoptosis induction were determined by using MTT assay and flow cytometry, respectively.Results: The respective rank of anticancer activity of Raphanus sativus were as follows:vegetative(3 week) < older rosette(4 week) < early-bolting(5 week) < senescence(7 week) < late-bolting(6 week). The low to high concentration of sulforaphene and sulforaphane occurred in the same stage order.Conclusions: The reproductive parts(flower, pod, and dry seed) of Raphanus sativus have the greatest isothiocyanate concentration, evidenced by a sulforaphene concentration higher than the sulforaphane. This result should inform the selection of the most appropriate harvesting stage and plant part for use as a potential chemopreventive agent.

Synthesis and Biological Evaluation of Novel Homopiperazine Derivatives as Anticancer Agents

In search of new anticancer agents, a series of novel 1-benzhydryl-4-(substituted phenylcarboxamide / carbothioamide)-1,4-diazepane derivatives were designed, synthesized and characterized using 1H NMR, LCMS and elemental analysis. These molecules were evaluated for their anti-cancer activity by trypan blue exclusion and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on B-cell leukemic cell line, Reh. Carboxamide moiety containing derivatives showed good activity compared to the corresponding carbothioamide derivatives. In particular, 4-benzhydryl-N-(3-chlorophenyl)-1,4-diazepane-1-carboxamide showed good activity with IC50 value of 18 μM.

Protective effects of Asian green vegetables against oxidant induced cytotoxicity

AIM： To evaluate the antioxidant and phase II detoxification enzyme inducing ability of green leaf vegetables consumed in Asia.METHODS： The antioxidant properties of six commonly consumed Asian vegetables were determined using the ABTS, DPPH, deoxyribose, PR bleaching and ironascorbate induced lipid peroxidation assay. Induce of phase II detoxification enzymes was also determined for each respective vegetable extract. Protection against authentic ONOO- and HOCl mediated cytotoxicity in human colon HCT116 cells was determined using the MTT 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrasodium bromide） viability assay.RESULTS： All of the extracts derived from green leaf vegetables exhibited antioxidant properties, while also having cytoprotective effects against ONOO- and HOCI mediated cytotoxicity. In addition, evaluation of the phase II enzyme inducing ability of each extract, as assessed by quinone reductase and glutathione- S-transferase activities, showed significant variation between the vegetables analyzed.CONCLUSION： Green leaf vegetables are potential sources of antioxidants and phase II detoxification enzyme inducers in the Asian diet. It is likely that consumption of such vegetables is a major source of beneficial phytochemical constituents that may protect against colonic damage.

Simple and Efficient Synthesis of Novel Glycosyl Thiourea Derivatives Derived from Thiophene as Potential Antitumor Agents

The practical synthesis of pseudonucleosides incorporating thiourea derivative by coupling of monosaccharides （D-glucose and D-galactose） per-O-acetylated glycosyl isothiocyanates and different heterocyclic hydrazide derivatives is reported. The method involves the preparation ofper-O-acetylated glycosyl isothiocyanates from per-O-acetylated sugars （two-step synthesis）, which couple with heterocyclic hydrazides from amines to give thiourea-linked pseudonucleosides. All newly synthesized pseudo-nucleosides were assayed against human lung cancer-cell lines （PG） and human liver cancer-cell lines （BEL-7402） in vitro. The 6,6-dimethyl-benzothiophen-3-carbo-hydrazide-4-one pseudonucleosides showed moderate inhibition against these two cancer-cell lines with ECs0 from 22.8 to 76.4 mM and from 54.9 to 82.4 mM, respectively. And the other compounds did not demonstrate any significant cytotoxicity even at concentrations up to 200 mM.

Synthesis, Characterization and Anti-Angiogenic Effects of Novel 5-Amino Pyrazole Derivatives on Ehrlich Ascites Tumor [EAT] Cells in-Vivo

In search of synthetic chemotherapeutic substances capable of inhibiting, retarding, or reversing the process of multi-stage carcinogenesis, we synthesized a series of novel 5-amino pyrazole derivatives 11(a-h) by a nucleophilic substitution reaction and characterized by 1H nuclear magnetic resonance (NMR), liquid chromatography mass spectrometry (LC/MS), Fourier-transform infrared (FTIR), and elemental analysis. These novel compounds were evaluated for their efficacy in inhibiting Ehrlich ascites tumor [EAT] cells in-vivo. In the present study we designed, synthesized, characterized and investigate the anti-angiogenic effects of these compounds, on Ehrlich ascites tumor [EAT] cells in-vivo. The compounds were subsequently tested for their ability to inhibit neovascularisation in chorio allantoin membrane (CAM) model. From the Structure Activity Relationship (SAR) studies, it reveals that, the substitution at N-terminal in pyrazole ring plays key role in the antitumor and anti-angiogenic effects.