Synthesis and cytotoxicity of metal 4-methyl-8-quinolinethiolates

It has been shown that the introduction of a methyl group at position 4 of the quinoline ring in metal 8-quinolinethiolates brings about a significant increase in the selectivity of their cytotoxic activity. It was found that rhodium 4-methyl-8-quinolinethiolate is 46 times less toxic than the unsubstituted 8-quinolinethiolate but with comparable toxicity towards MG-22A tumor cells (LC₅₀ 2 μg/ml). __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 755–758, May, 2007.     

Synthetic transformation of higher terpenoids 31. Synthesis of 1,2,3-triazolyl-containing furan labdanoids and studies of their cytotoxic activity

16-(1-R-1,2,3-Triazol-4-ylethyl)-, 16-(1-R-1,2,3-triazol-4-ylmethoxymethyl)-, and 16-{2-(1-R-1,2,3-triazol-4-yl)-1-[(1-R-1,2,3-triazol-4-ylmethoxy)ethyl]}-substituted derivatives of methyl lambertianate were synthesized by 1,3-cycloaddition of labdanoid alkynes with azides. The compounds obtained possess considerable cytotoxicity toward the human tumor cell lines CEM-13, MT-4, and U-937. The most active compound, methyl 16-(2-{2-[(1-benzyl-1H-1,2,3-triazol-4-yl)acetyl]furan-3-yl}ethyl)lambertianate, was found to inhibit the viability of the tumor cells by 50% (CCID₅₀) in the concentration of 7–12 μmol L^?1.     

Design,synthesis of novel N prenylated indole-3-carbazones and evaluation of in vitro cytotoxicity and 5-LOX inhibition activities

A series of novel N-1 and C-3 substituted indole derivatives (5a–f) were designed, synthesized and evaluated for their cytotoxic properties, viz Brine Shrimp Lethality Bioassay (BSLB) besides 5-Lipoxygenase (5-LOX) inhibitory activities through in vitro assays. Structure Activity Relation (SAR) studies showed that compound 5d with an LC₅₀ of 6.49 μM and 5c with an IC₅₀ of 33.69 μM were found to be interesting for cytotoxicity and 5-LOX inhibitory activity respectively.     

Benzimidazo[1,2-c]quinazoline dimers as potential antitumor agents

The 6-substituted benzimidazo[1,2-c]quinazoline 1 is a lead structure from our DNA intercalator program and is cytotoxic to the human colon cancer tumor line HT-29 with an inhibitory concentration 50, IC₅₀ of 4.00 μM. In order to try and improve the limited cytotoxicity of this class of compound we prepared a series consisting of two benzimidazo[1,2-c]quinazoline moieties linked by a polyalkylamino bridge, of different length and substitution. The compound with the -NH-(CH₂)₃-N(CH₃)-(CH₂)₃-NH-bridge had an inhibitory concentration 50, IC₅₀ of 0.5 μM. When tested in vivo, however, no clear anti-tumor activity was produced in the human breast cancer tumor line MX-1 or the human melanoma tumor line LOX, human tumor xenografts models.     

Synthesis and cytotoxicity of complex compounds of tin, vanadium, and molybdenum with quinolinethiol and its methyl and methoxy derivatives

A series of 8-quinolinethiolates, and 3-methyl-, 4-methyl-, 5-methyl-, 6-methyl-, 7-methyl-, and 6-methoxy-8-quinolinethiolates of tin(II), vanadium(IV), and molybdenum(VI) has been synthesized. Their cytotoxicity on HT-1080 tumor cells (human fibrosarcoma) and MG-22A (mouse hepatoma) cells has been studied. It was established that all of the investigated complexes of 8-quinolinethiol and majority of the complexes of 8-quinolinethiol derivatives possessed very high cytotoxicity towards both cell lines. Their toxicity in relation to mouse embryo fibroblasts NIH 3T3 depended on the position of the substituent in the quinoline ring. Complexes of tin and vanadium with 4-methyl-, 5-methyl-, and 6-methoxy-8-quinolinethiol derivatives were less toxic. 4-Methyl-, 5-methyl-, and 6-methoxy-8-quinolinethiolates of vanadium demonstrated the highest selectivity of cytotoxic action.     

Design,syntheses and antitumor activities evaluation of 1,5-diaryl substituted pyrazole secnidazole ester derivatives

According to the drug hybridization principle, a series of novel 1,5-diaryl substituted pyrazole secnidazole ester derivatives ( 6aa – 6gc ) have been synthesized by the combinations of various 1,5-diarylpyrazole-3-carboxylic acids with secnidazole. The in vitro antitumor/cytotoxicities activities against tumor and normal cell lines, including NCI-H460 (lung tumor cell), MCG-803 (gastric tumor cell), Skov-3 (ovarian tumor cell), BEL-7404 (liver tumor cell) and HL-7702 (normal liver cell), have been evaluated using MTT assay. All compounds showed promising inhibitory activities against four tumor cell lines. The IC₅₀ of 6bc against the BEL-7404 cell was 2.03 μM, and those of 6fc against the NCI-H460, MCG-803 and Skov-3 were 1.34, 0.14, and 0.87 μM, respectively. All these values were much lower than those of the cisplatin. Furthermore, 6fc and 6bc were also verified to be considerably safe for normal human liver cell, since the lower IC₅₀ values than cisplatin. Based on these results, the cell cycle analysis, apoptosis ratio detection and mitochondrial membrane potential assay of 6fc and 6bc were further performed aiming to investigate their inhibition mechanism of BEL-7404 cells. It is revealed that they have effectively inhibited the cell growth by arresting the BEL-7404 cells at S phase and induced apoptosis through the mitochondria-mediated pathway.     

Novel coumarin derivatives containing 1,2,4-triazole, 4,5-dicyanoimidazole and purine moieties: synthesis and evaluation of their cytostatic activity

We report here on the synthesis and in vitro anti-tumor effects of a series of novel 1,2,4-triazole (compounds 3-6), 4,5-dicyanoimidazole (compound 7), and purine (compounds 8-13) coumarin derivatives and their acyclic nucleoside analogues 14-18. Structures of novel compounds 3-18 were deduced from their ¹H- and ¹³C-NMR and corresponding mass spectra. Results of anti-proliferative assays performed on a panel of selected human tumor cell lines revealed that compound 6 had moderate cytostatic activity against the HeLa cell line (IC₅₀ = 35 μM), whereas compound 10 showed moderate activity against the HeLa (IC₅₀ = 33 μM), HepG2 (IC₅₀ = 25 μM) and SW620 (IC₅₀ = 35 μM) cell lines. These compounds showed no cytotoxic effects on normal (diploid) human fibroblasts.     

A Brief Review of the Anticancer Activity of α-Aminophosphonic Acid Derivatives and a Report on the in Vitro Activity of Some Dialkyl α-aryl- (or Heteroaryl)-α-(Diphenylmethylamino)Methanephosphonates

Abstract

Reports on the anticancer activity of representative α-aminophosphonic acid derivatives are briefly reviewed, with comments where possible on modes of action. Preliminary in vitro screening results are also presented for selected dialkyl α-aryl (or heteroaryl)-α-(diphenylmethylamino)methanephosphonates against the National Cancer Institute (NCI) 60-cell line panel of human tumor cells, which showed average response parameters for active compounds of GI₅₀ between 4.81 × 10^?6 and 2.40 × 10^?5 M, TGI between 1.88 and 6.28 × 10^?5 M, and LC₅₀ between 5.71 and 9.37 × 10^?5 M. The highest activity was shown by the α-phenyl compound for which GI₅₀ 10^?7 M was recorded against leukemia cell line MOLT-4.     

Immunotoxicity of Organic Arsenic Compounds in Marine Animals

In the present study, we demonstrated for the first time the immunotoxic effects of organic arsenic compounds in marine animals, namely arsenocholine [AsCho; trimethyl(2-hydroxyethyl)arsonium cation], arsenobetaine [AsBe; the trimethyl(carboxymethyl)arsonium zwitterion] and the tetramethylarsonium ion (TetMA), to murine principal immune effector cells (macrophages and lymphocytes), comparing them with the effects of inorganic arsenicals in vitro . Inorganic arsenicals (arsenite and arsenate) showed strong cytotoxicity to both macrophages and lymphocytes. The concentration of arsenite that reduced the number of surviving cells to 50% of that in untreated controls (IC₅₀) was 3–5 μmol dm⁻³, and the cytotoxicity of arsenate (IC₅₀=100 μ-1 m mol dm⁻³) was lower than that of arsenite. Compared with these findings, trimethylarsenic compounds in marine animals, AsCho and AsBe, were less toxic even at a concentration over 10 mmol dm⁻³ to both macrophages and lymphocytes; however, TetMA had weak, but significant, cytotoxicity to these cells (IC₅₀ was about 6 mmol dm⁻³).     

Nucleus‐Targeted Organoiridium–Albumin Conjugate for Photodynamic Cancer Therapy

An organoiridium–albumin bioconjugate ( Ir1‐HSA ) was synthesized by reaction of a pendant maleimide ligand with human serum albumin. The phosphorescence of Ir1‐HSA was enhanced significantly compared to parent complex Ir1 . The long phosphorescence lifetime and high ¹O₂ quantum yield of Ir1‐HSA are highly favorable properties for photodynamic therapy. Ir1‐HSA mainly accumulated in the nucleus of living cancer cells and showed remarkable photocytotoxicity against a range of cancer cell lines and tumor spheroids (light IC₅₀; 0.8–5 μm , photo‐cytotoxicity index PI=40–60), while remaining non‐toxic to normal cells and normal cell spheroids, even after photo‐irradiation. This nucleus‐targeting organoiridium‐albumin is a strong candidate photosensitizer for anticancer photodynamic therapy.     

Triphenylamine‐Appended Half‐Sandwich Iridium(III) Complexes and Their Biological Applications

Organometallic half‐sandwich Ir^III complexes of the type [(η⁵‐Cp^x)Ir(N^N)Cl]PF₆ (Cp^x: Cp* or its phenyl Cp^xph or biphenyl Cp^xbiph derivatives; N^N: triphenylamine (TPA)‐substituted bipyridyl ligand groups) were synthesized and characterized. The complexes showed excellent bovine serum albumin (BSA) and DNA binding properties and were able to oxidize NADH to NAD⁺ (NAD=nicotinamide adenine dinucleotide) efficiently. The complexes induced apoptosis effectively and led to the emergence of reactive oxygen species (ROS) in cells. All complexes showed potent cytotoxicity with IC₅₀ values ranging from 1.5 to 7.1 μm toward A549 human lung cancer cells after 24 hours of drug exposure, which is up to 14 times more potent than cisplatin under the same conditions.     

Allyl palladium complexes bearing carbohydrate-based N-heterocyclic carbenes: Anticancer agents for selective and potent in vitro cytotoxicity

Novel allyl palladium compounds stabilized by carbohydrate-based N-heterocyclic carbenes (NHCs) were prepared and characterized by nuclear magnetic resonance, high-resolution mass spectrometry and elemental analysis. The antiproliferative activity of the compounds was tested on a panel of different tumor lines, especially ovarian cancer and MRC-5 human lung fibroblasts (nontumor cells). These experiments showed that both mixed NHC/PPh₃ and NHC/PTA (PTA = 1,3,5-triaza-7-phosphaadamantane) allyl complexes have IC₅₀ (half maximal inhibitory concentration) values comparable and sometimes even significantly lower than cisplatin. Moreover, the mixed NHC/PTA allyl complexes exhibit good activity toward the seven tumor lines tested with a substantial inactivity against normal cells, a necessary condition to avoid the general cytotoxicity of a metallo-drug. Furthermore, this subclass of compounds proved particularly active on the A549 lung cancer tumor line (up to 100-fold more cytotoxic than cisplatin) and exhibited satisfactory cytotoxicity against KURAMOCHI and OVCAR3 cell lines, which are currently considered the best in vitro models for serous ovarian cancer, the most lethal tumor for women worldwide.     

Insecticidal effects of organotin(IV) compounds on Plutella xylostella (Linnaeus) larvae I: Topical application toxicity and antifeedant effect

Structure–activity relationship studies were conducted with early fourth-instar larvae of a highly resistant strain of the diamondback moth, Plutella xylostella (Linnaeus) on (1) toxicity by topical appliction of 43 organotin compounds, and (2) the antifeedant effect of a selected number (17) of these compounds on treated Brassica chinensis (Chinese cabbage) leaves. The toxicity data revealed that the triorganotins (R₃SnX) were, without exception, more toxic than the commercial sample of malathion (84% active ingredient) used in the tests. Among the diorganotins, phenylcyclopentyltin oxide proved to be as active as malathion. Within the triorganotin series, the tricyclohexyltins were generally more toxic than the triphenyltins, the most active tricyclohexyltin compound being (c-C₆H₁₁)₃Sn(2-pyridinethiolato N-oxide) (LC₅₀ 0.03 μg μl^?1), which was almost 500-fold more active than malathion. The most active compound in the triphenyltin class was O, S-bis(triphenyltin)mercaptoacetate (LC₅₀ 0.30 μg μl^?1). Variations in the anionic X group resulted only in marginal changes in activity in the (c-C₆H₁₁)₃Sn series, but significant changes in activity were obtained with the Ph₃Sn compounds, especially the ring-substituted phenoxyacetates, (4-ZC₆H₄)OCH₂(O)COSnPh₃. In the mixed triorganotin compounds an increase in activity was observed when one of the phenyl groups in Ph₃SnOH was replaced by the p-chlorophenyl group. In the antifeedant tests, the tricyclohexyltins were found to be generally more effective than the triphenyltins. In most cases, antifeedant activity paralleled the toxicity by topical application trends in the (c-C₆H₁₁)₃Sn series, but in the Ph₃Sn series an inverse trend was observed. The diorganotin compound (c-C₅H₉)PhSnO exerted a relatively pronounced antifeedant activity which was comparable with that of a number of triphenyltin derivatives. It was established from histological studies of the mid-gut cross-sections of the treated larvae that, in most cases, the organotins affected the columnar cells physiologically; an exception was noted for Ph₃SnOC(O)C₆H₄COOH-4 which, like malathion, caused severe morphological damage to the cell membrane.     

Semisynthetic derivatives of haemanthamine and their in vitro antiproliferative activity evaluation against a panel of human cell lines

In this study, a new series of aliphatic, cyclic, and heterocyclic derivatives of haemanthamine was designed and synthesized to enhance its inhibitory effect on the proliferation and viability of cancer cells. A library of haemanthamine derivatives was subjected to 10 μM single-dose cytotoxicity screening against a panel of human cell lines of various histotypes. Initial cytotoxicity evaluation of the parent haemanthamine (1) and a series of twenty-nine (2–30) semisynthetic analogues showed that for some of the newly formed derivatives, a certain cytotoxic effect was observed, in one case even higher than that of the parent compound. Specifically, 11-O-(4-chloro-3-nitrobenzoyl)haemanthamine (21) showed an enhanced antiproliferative effect, where the mean growth percent (GP) value was 5% compared to haemanthamine, leading to a decrease in the GP to 25%. Among ten cell lines tested, derivative 21, bearing a substituted aromatic ester bond via C-11 of haemanthamine, had excellent activity for inhibiting the growth of HeLa (IC₅₀ = 0.2 ± 0.1 μM), A549 (IC₅₀ = 1.7 ± 0.1 μM) and HT-29 (IC₅₀ = 2.2 ± 0.1 μM) cells. When evaluating response kinetics, we found that 21 and haemanthamine dose- and time-dependently suppressed the proliferation of A549 cells. In contrast to haemanthamine (1), Trypan blue and lactate dehydrogenase (LDH) release assay revealed that 21 was capable of reducing the survival of A549 cells.     

Convenient method for the synthesis of some novel chiral methyl 2-(2-oxo-2H-benzo[e][1,3]oxazin-3(4H)-yl)propanoate derivatives and biological evaluation of their antioxidant,cytotoxic, and molecular docking properties

Ten chiral methyl 2-(2-oxo-2H-benzo[e][1,3]oxazin-3(4H)-yl)propanoate derivatives 6a-6j have been synthesized from optically pure amino methyl phenol 5 and 4-nitrophenyl chloroformate. These derivatives 6a-6j are characterized by ¹H NMR, ¹³C NMR, FT-IR, and HRMS spectral techniques. Optical purity of these derivatives was confirmed by chiral HPLC method. Ten synthesized ester derivatives 6a-6j were screened for their in vitro antioxidant activity. Among the compounds 6b-d and 6h-j have exhibited comparable antioxidant activity with ascorbic acid as a standard. Compounds 6a and 6e-g have shown moderate antioxidant activity. Further, the in vitro cytotoxicity of these compounds were studied through MTT cell proliferation assay in addition the effect on LDH leakage and NO release. Among the derivatives, 6j showed extremely best activity and the IC₅₀ value (12.54 ± 0.71 μM) is very close to doxorubicin (7.2 ± 0.58 μM) as a standard. Compounds 6b , 6h , and 6i showed better inhibition next to compound 6j on the viability of HepG2 cells with an IC₅₀ value (μM) of 56.02 ± 1.4, 41.76 ± 0.58, and 38.17 ± 0.34, respectively. Also, molecular docking studies have been carried out with STAT-3 (PDB ID: 1BG1) and BCL-2 (PDB ID: 4AQ3) proteins against the four active compounds 6b , 6h , 6i , and 6j . The binding energies of the tested compounds were in the range of −7.76 to −8.41 kcal/mol, which is very close to doxorubicin (−8.53 kcal/mol) as a standard. These molecular docking results are in good agreement with the in vitro studies.     

Design,Synthesis, and In Vitro Antileishmanial and Antitumor Activities of New Tetrahydroquinolines

A novel series of tetrahydroquinolines containing acetohydrazide, oxopyrazole, oxothioxodihydropyrazole, and thioxotriazole have been synthesized. Antileishmanial, antitumor, and cytotoxicity activities of synthesized compounds were evaluated in vitro. Antileishmanial activity of the most synthesized compounds showed tremendous activity towards Leishmania major. Most of the test compounds exhibited significant level of tumor inhibition. The tetrahydropyrano[2,3‐b]quinolin‐2‐one 6 and 4‐oxo‐4H‐pyrazol‐3‐yloxytetrahydroquinoline‐3‐carbonitrile derivatives 18 showed 100% tumor inhibition comparable with standard drug vincristine (100% tumor inhibition). Tetrahydroquinolines under investigation showed cytotoxicity with LD₅₀ values in the range 0.56–3.01 μg/mL compared with standard drug MS‐222 with LD₅₀ value of 4.30 μg/mL. The presence of a pyrazole ring markedly improved the activity profiles of tetrahydroquinoline. All newly synthesized compounds were characterized by IR, ¹H NMR, and MS.     

Ferrocene conjugated copper(II) complexes of terpyridine and traditional Chinese medicine (TCM) anticancer ligands showing selective toxicity towards cancer cells

Six novel mixed‐ligand copper(II) complexes, namely, [Cu(R‐tpy)(L)]NO₃ ( 1–6 ), where R‐tpy is 4′‐phenyl‐2,2′:6′,2′′‐terpyridine (Ph‐tpy; 1–3 ) and 4′‐ferrocenyl‐2,2′:6′,2′′‐terpyridine (Fc‐tpy; 4–6 ), L is the bidentate O,O donor monoanion of plumbagin (5‐hydroxy‐2‐methyl‐1,4‐naphthoquinone; plum in 1 , 4 ), chrysin (5,7‐dihydroxyflavone; chry in 2 , 5 ) and curcumin (bis(4‐hydroxy‐3‐methoxyphenyl)‐1,6‐diene‐3,5‐dione; curc in 3 , 6 ) have been synthesized and characterized and their in vitro cytotoxicity against cancer cells is evaluated. The energy optimized structures and the frontier orbitals of the complexes have been obtained from the DFT calculations. Complexes 4–6 with a conjugated ferrocenyl moiety and TCM anticancer ligands, namely, plum (in 4 ), chry (in 5 ) and curc (in 6 ) showed potent cytotoxicity giving respective IC₅₀ values of 1.2 μM, 0.62 μM and 0.21 μM in HeLa and 2.0 μM and 1.0 μM and 0.34 μM in MCF‐7 cancer cells while being much less toxic to MCF‐10A normal cells (IC₅₀: 8.3‐17.1 μM). In contrast, complexes 1–3 with a conjugated phenyl moiety were appreciably less toxic to HeLa cells with respective IC₅₀ values of 10.4 μM, 8.1 μM and 5.5 μM when compared with their ferrocenyl analogues 4–6 . Mechanistic studies using Hoechst staining and Annexin‐V‐FITC assays on cancer cells revealed an apoptotic pathway of cell death induced by the complexes. Fluorescence imaging study showed that complex 6 having curcumin as ligand localized primarily in the mitochondria of HeLa cells. Thus, we demonstrate in this study that ferrocene conjugation to copper(II) complexes of TCM anticancer ligands significantly increases the selectivity and cytotoxicity of the resulting complexes towards cancer cells over normal cells.     

Synthesis and cytotoxicity of methyl-substituted 8-quinolineselenolates of ruthenium,rhodium, osmium,and iridium

A series of 2-methyl, 4-methyl, and 2,4-dimethyl-8-quinolineselenolates of ruthenium, rhodium, osmium, and iridium has been synthesized and their cytotoxicity towards HT-1080 (human fibrosarcoma) and MG-22A (mouse hepatoma) tumor cells studied. It was found that all of the osmium complexes had a high cytotoxicity towards both cell lines. Their toxicity towards the normal mouse embryonic fibroblasts NIH-3T3 depends on the position and number of methyl groups in the quinoline ring and decreases in the order 2-Me > 4-Me > 2,4-Me₂. The greatest selectivity in cytoxic activity is noted for iridium 4-methyl-8-quinolineselenolate and ruthenium 2-methyl-8-quinolineselenolate. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 230–236, February, 2009.     

Influence of Halogen Substitution in the Ligand Sphere on the Antitumor and Antibacterial Activity of Half‐sandwich Ruthenium(II) Complexes [RuX(η6‐arene)(C5H4N‐2‐CH=N‐Ar)]+

New complexes [(η⁶‐p‐cymene)Ru(C₅H₄N‐2‐CH=N–Ar)X]PF₆ [X = Br ( 1 ), I ( 2 ); Ar = 4‐fluorophenyl ( a ), 4‐chlorophenyl ( b ), 4‐bromophenyl ( c ), 4‐iodophenyl ( d ), 2,5‐dichlorophenyl ( e )] were prepared, as well as 3a – 3e (X = Cl) and the new complexes [(η⁶‐arene)RuCl(N‐N)]PF₆ (arene = C₆H₅OCH₂CH₂OH, N‐N = 2,2′‐bipyridine ( 4 ), 2,6‐(dimethylphenyl)‐pyridin‐2‐yl‐methylene amine ( 5 ), 2,6‐(diisopropylphenyl)‐pyridin‐2‐yl‐methylene amine ( 6 ); arene = p‐cymene, N‐N = 4‐(aminophenyl)‐pyridin‐2‐yl‐methylene amine ( 7 )]. X‐ray diffraction studies were performed for 1a , 1b , 1c , 1d , 2b , 5 , and 7 . Cytotoxicities of 1a – 1d and 2 were established versus human cancer cells epithelial colorectal adenocarcinoma (Caco‐2) (IC₅₀: 35.8–631.0 μM), breast adenocarcinoma (MCF7) (IC₅₀: 36.3–128.8.0 μM), and hepatocellular carcinoma (HepG2) (IC₅₀: 60.6–439.8 μM), 3a – 3e were tested against HepG2 and Caco‐2, and 4 – 7 were tested against Caco‐2. 1 – 7 were tested against non‐cancerous human epithelial kidney cells. 1 and 2 were more selective towards tumor cells than the anticancer drug 5‐fluorouracil (5‐FU), but 3a – 3e (X = Cl) were not selective. 1 and 2 had good activity against MCF7, some with lower IC₅₀ than 5‐FU. Complexes with X = Br or I had moderate activity against Caco‐2 and HepG2, but those with Cl were inactive. Antibacterial activities of 1a , 2b , 3a , and 7 were tested against antibacterial susceptible and resistant Gram‐negative and ‐positive bacteria. 1a , 2b , and 3a showed activity against methicillin‐resistant S. aureus (MIC = 31–2000 μg · mL^–1).     

3-芳基噻唑烷-4-酮-2-酰胺的合成及其抗肿瘤活性研究

合成了系列新的3-芳基噻唑烷-4-酮-2-酰胺衍生物,并测试了化合物抑制肿瘤细胞增殖活性.部分化合物对A-549和Hela肿瘤细胞有弱的细胞毒性,而对BGC-823没有抑制作用,表现出一定的选择性.其中,化合物7ad对A-549有较强的抑制活性(IC50=21.0μmol·L-1),与阳性对照顺铂的抑制活性(IC50=19.4μmol·L-1)相当.初步的构效关系表明化合物的立体结构可能对其抗肿瘤活性影响较大.