(1iR,1iiR,2iR,2iiR)-Ni,Nii-(1,3-亚苯基双(亚甲基))环己烷-1,2-二胺作为配体的双核铂配合物的合成及其抗癌活性

以(1ⁱR,1ⁱⁱR,2ⁱR,2ⁱⁱR)-Nⁱ,Nⁱⁱ-(1,3-亚苯基双(亚甲基))环己烷-1,2-二胺(HL)作为配体,设计并合成了7种双核铂配合物,并利用IR,¹H NMR,¹³C NMR,ESI-MS和元素分析等进行了表征。通过MTT法测定目标双核铂配合物对人类HepG-2,A549,HCT-116和MCF-7四种癌细胞系的细胞毒性。结果表明,所有的化合物对HepG-2,A549和HCT-116细胞系均表现了良好的细胞毒活性,但对MCF-7细胞系均无活性。其中,以3-羟基环丁烷-1,1-二羧酸为离去基团的配合物P7对HepG-2和A549细胞系的活性优于卡铂,对HCT-116细胞系的活性接近于奥沙利铂。     

缩氨基硫脲Ni（Ⅱ）配合物的合成、晶体结构、DNA相互作用及抗肿瘤活性研究

合成了一种缩氨基硫脲Ni（Ⅱ）配合物[Ni（QCMT）₂]Cl₂·2CH₃OH·1.5H₂O（QCMT为喹啉-2-甲醛-N⁴-甲基缩氨基硫脲）。该配合物晶体属于三斜晶系,P1空间群,a=1.0002（2）nm,b=1.0939（2）nm,c=1.5836（3）nm,α=93.99（3）°,β=105.25（3）°,γ=108.46（3）°。中心离子Ni²⁺处于变形八面体配位环境中。电子吸收光谱、荧光光谱及圆二色谱分析表明该配合物通过静电作用方式与DNA相结合。测定了该Ni（Ⅱ）配合物与配体（QCMT）对人乳腺癌细胞系MCF-7、人卵巢癌细胞系SKOV-3及人非小细胞肺癌耐顺铂细胞系A-549/CDDP的体外细胞毒活性。结果表明,Ni（Ⅱ）配合物对MCF-7细胞系的细胞毒活性强于顺铂,同时该配合物对MCF-7和SKOV-3两种细胞系的细胞毒活性明显优于其配体。     

多羟基甾醇25(R)-异螺甾环-5-烯-2β,3α,19-三醇的合成

以薯蓣皂素为原料, 经过磺酰酯化、N-溴代丁二酰亚胺(NBS)氧化加成、Pb(OAc)₄远程氧化关环、消去反应、间氯过氧苯甲酸(mCPBA)氧化、高氯酸开环及锌粉还原7步反应, 合成多羟基甾体25(R)-异螺甾环-5-烯-2β,3α,19-三醇. 并用IR, ¹H NMR, ¹³C NMR, MS及元素分析对各中间体及目标化合物进行了表征.     

N, N’-双(3-吡啶醛)-(1R, 2R)-环己二胺席夫碱Ag(Ⅰ)配合物的合成、结构和荧光性质研究

以3-吡啶醛和（1R,2R）-环己二胺进行缩合得到Schiff碱配体L¹,然后,用配体L¹和AgNO₃进行配位反应,得到配合物[Ag（L¹）（NO₃）]_n（1）,并用元素分析、FT-IR、X-射线单晶衍射、热重分析、粉末衍射对其进行了表征。晶体结构表明：配合物1属于单斜晶系,C2空间群,Ag（Ⅰ）的配位环境均为扭曲四面体,分别和硝酸根的氧原子,配体中的2个吡啶氮原子以及1个亚胺氮原子配位,配体L¹有2种配位模式,其中,1个配体用两臂的2个吡啶氮原子分别和2个Ag（Ⅰ）离子配位,另外1个配体用两臂的2个吡啶氮原子分别和2个Ag（Ⅰ）离子配位,同时2个亚胺氮原子也分别和2个Ag（Ⅰ）离子配位,这样配合物形成3D孔状结构。同时研究了配合物的固体荧光性质。     

不对称大环双核铜(Ⅱ)配合物[Cu2(C23H26Cl2N4O2)](ClO4)2的合成、晶体结构及磁性

大环双核铜(Ⅱ)配合物由N,N′-二甲基-N,N′-二(3-甲酰基-5-氯水杨醛)乙二胺和1,3-丙二胺,与铜(Ⅱ)反应形成的,经过X-射线单晶衍射结果表明：a=0.871 05(16) nm,b=0.957 78(18) nm,c=1.810 4(3) nm,β=100.761(18)°,V=1.483 8(5) nm³,Z=2,D_c=1.762 Mg·m^-3,μ=1.85 mm^-1,F(000)=796,and final R₁=0.061,wR₂=0.126。晶体结构表明：两个铜离子位于双核大环中间,与大环的胺、亚胺以及酚羟基的氧进行配位。磁性结果表明配合物为反铁磁性。     

烷氧基酸为离去基团的铂(Ⅱ)配合物的体外活性研究

合成了5个以直链和带支链烷氧基乙酸为载体配基的顺铂类配合物,通过红外光谱、核磁共振氢谱和质谱对配合物进行了表征,并测试了化合物对肺腺癌SPC-A1和胃腺癌BGC823的体外抗肿瘤活性。生物活性测试结果表明,配合物的活性与离去基团有很大关系。配合物4(顺-二(异丙氧基乙酸根)·[(1R,2R)-1,2-反式环己二胺]合铂(Ⅱ))在2个细胞系中均显示最高的体外抗肿瘤活性,甚至超过顺铂。     

1R，3S-1，2，2-三甲基-1，3-环戊二胺为配体的铂(Ⅱ) 配合物的合成、表征和抗肿瘤活性

本文合成了9种含有由天然D(+)-樟脑衍生的1R，3S-1，2，2-三甲基-1，3-环戊二胺(A)为配体的铂(Ⅱ)配合物[Pt(Ⅱ)AX]{其中，X=(CH₂)₃C(COO^-)₂(1，1-环丁烷二羧酸根)，2CH₃OCH₂COO^-，2CH₃CH₂OCH₂COO^-，2CH₃(CH₂)₃OCH₂COO^-，[OCH(CH₃)COO]^2-(乳酸根)，(OCH₂COO)^2-(乙醇酸根)，2CH₃OCH₂CH₂OCH₂COO^-，2CH₃CH₂OCH₂CH₂OCH₂COO^-和2CH₃(CH₂)₃OCH₂CH₂OCH₂COO^-}。通过元素分析、热重分析、红外光谱、¹H核磁共振谱和电喷雾质谱等对配合物进行了表征。体外生物活性测试表明，部分配合物对A549人肺癌细胞和HCT-116人结肠癌细胞具有较强的抗肿瘤活性。     

［Eu2(o-ClC6H4OCH2COO)6(C12H8N2)2(H2O)2］·(CH3)2SO的晶体结构和荧光光谱

标题配合物M=1892.01,单斜晶系,空间群P2₁/c, a=1.2975(3) nm, b=2.6591(9) nm, c=1.2118(3) nm, β=96.95(1)°, Z=2, D_c=1.577 g/cm³, T=293(2)K。最终的偏离因子R=0.0583。该配合物以二聚体形式存在,通过其中的桥联羧基形成了双核分子。该分子中羧基具有桥联双齿、桥联三齿和单齿三种配位模式,Eu-Eu之间的距离为0.4019(1) nm。在77K下测得配合物中Eu(Ⅲ)离子仅有一种格位。 ⁵D₀→ ⁷F_J(J=0～2)跃迁光谱说明Eu(Ⅲ)离子格位具有C₂对称性。     

N-{2-氯-5-[3-甲基-2,6-二氧-4-三氟甲基-2,3-二氢嘧啶-1(6H)-基]苯基}酰胺类化合物的合成及除草活性

为了寻找高效、安全的除草活性化合物, 合成了12个全新的N-{2-氯-5-[3-甲基-2,6-二氧-4-三氟甲基-2,3-二氢嘧啶-1(6H)-基]苯基}酰胺类化合物, 其化学结构经IR, ¹H NMR, LC/MS和元素分析确证. 初步生物活性测定结果表明, 该类化合物具有一定的除草活性, 如7a, 7b, 7c, 7g, 7h, 7i, 7k和7l在有效成分75 g/hm²剂量下, 茎叶处理对苘麻(Abutilon theophrasti)、刺苋(Amaranthus spinosus)等阔叶杂草具有良好的除草活性, 其抑制率达100%.     

p,p′-芳炔桥连的四联萘拓扑环芳分子的设计与合成

基于联萘衍生物手性构型高度稳定的特点, 以光学活性的(R)-2,2'-二乙炔基-1,1'-联萘为模板, 设计了3个有趣的拓扑环芳分子——含有4个手性联萘单元的(R,R,R,R)-2a～2c, 并探讨了它们的合成. 合成路线涉及三甲基硅(Me₃Si-)保护基的控制导入, 对位取代的芳基连接桥的链接, 保护基的脱去以及分子间偶合成环4个步骤. 用比旋光度([α]_D), MS, IR, UV-Vis, ¹H和¹³C NMR以及元素分析表征了这些化合物.     

Synthesis and in vitro cytotoxicity of novel dinuclear platinum(II) complexes containing a chiral tetradentate ligand

A series of novel dinuclear platinum(II) complexes with a chiral tetradentate ligand, (1R,1′R,2R,2′R)-N¹,N¹′-(1,2-phenylenebis(methylene))dicyclohexane-1,2-diamine (HL), and mono-carboxylic acid derivatives as ligands have been designed, synthesized, and characterized. In vitro cytotoxicity evaluation of synthesized complexes against human HepG-2, A549, HCT-116, and MCF-7 cancer cell lines has been conducted by MTT assays. All compounds showed antitumor activity to HepG-2 and HCT-116 cell lines. Compound L2 exhibited better cytotoxicity than that of carboplatin against HepG-2 and A549 cell lines and also showed comparable activity against HCT-116 cell line.     

Synthesis and in vitro cytotoxicity of platinum(II) complexes with chiral N-monosubstituted 1,2-cyclohexyldiamine derivatives as the carrier groups

Eight platinum(II) complexes with the new chiral ligands, (1R,2R)-N ¹-(pyridine-2-ylmethyl) cyclohexane-1,2-diamine (R) or (1S,2S)-N ¹-(pyridine-2-ylmethyl) cyclohexane-1,2-diamine (S) as the carrier groups were designed, synthesized, and spectrally characterized. All platinum(II) complexes showed much better aqueous solubility than cisplatin and oxaliplatin. In vitro cytotoxicity of the compounds against human HepG-2, MCF-7, A549, and HCT-116 cell lines was evaluated. Results indicate that all compounds with R as the carrier group showed cytotoxicity against HCT-116, A549, and MCF-7 cell lines; however, all compounds with S as carrier group exhibited disappointing cytotoxicity against tested cell lines. Compound R2, bearing ClCH₂COO^- as leaving group, exhibited better cytotoxicity than that of carboplatin against A549 and MCF-7 cell lines and also showed close activity to oxaliplatin against HCT-116 cell line.     

Synthesis, characterization and biological evaluation of platinum(II) complexes with a chiral N-monosubstituted 1,2-cyclohexyldiamine derivative

Eight platinum(II) compounds with a new chiral ligand, 2-(((1R,2R)-2-aminocyclohexylamino)methyl)phenol (HL), were designed, prepared and spectrally characterized. All compounds showed better aqueous solubility than cisplatin and oxaliplatin. In vitro cytotoxicity of these compounds against human HepG-2, MCF-7, A549 and HCT-116 cell lines was evaluated. Results indicated that all compounds showed cytotoxicity against A549 and HepG-2 cell lines. Particularly, compounds B1 and B8, which have CF?SO?? and (CH?)?COCH?COO(-) as leaving groups, respectively, exhibited better cytotoxicitiy than that of carboplatin in these two cell lines.     

Preparation and in vitro cytotoxicity of oxaliplatin derivatives with chiral amino acid as the carrier group

Eight oxaliplatin derivatives with chiral amino acid, 2-{[(1R,2R)-2-aminocyclohexyl]amino}propanoic acid, as the carrier group, were designed, synthesized, and spectrally characterized by IR, ¹H NMR, MS spectra, and microanalyses. In vitro cytotoxicities against human HepG-2, MCF-7, A549, and HCT-116 cell lines were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazo-liumbromide assay. Results indicated that all compounds exhibited sensitivity to HepG-2 cell line, and among them, compounds P3 and P4 which have CH₃(CH₂)₆COO^– and CH₃(CH₂)₈COO^– as the leaving groups, respectively, gave better antitumor activity than carboplatin against HepG-2 and A549 cell lines.     

Synthesis and biological evaluation of water-soluble trans-[bicyclo[2.2.2]octane-7R,8R-diamine]platinum(II) complexes with linear or branched alkoxyacetates as leaving groups

Four platinum(II) complexes, trans-[bicyclo[2.2.2]octane-7R,8R-diamine]bis(alkoxyacetato-O,O’) platinum(II) (alkoxyacetate = methoxyacetate (2), ethoxyacetate (3), isopropoxyacetate (4), and tert-butoxyacetate (5)) were synthesized and spectrally characterized. The cytotoxicity of these water-soluble complexes was evaluated by CCK-8 assay in vitro against HCT-116, HepG-2, and A549 cancer cell lines. Most of the complexes had cytotoxic activity against the tested cancer cell lines. Among them, 3 showed more potent antitumor effect than cisplatin or oxaliplatin. Complex 3 could cause HCT-116 cell line death based on an apoptotic pathway since it has a dicyclic moiety similar to 1R,2R-diaminocyclohexane in oxaliplatin. Agarose gel electrophoresis on the interaction between 3 and DNA indicated that it has different behavior from that of cisplatin or oxaliplatin, which has a high correlation with the ligand used.     

Novel antitumor dinuclear platinum (II) complexes with a new chiral tetradentate ligand as the carrier group

Seven dinuclear platinum(II) complexes with a novel chiral tetradentate ligand, (1R,1′R,2R,2′R)‐N¹,N^1′‐(1,4‐phenylenebis(methylene))dicyclohexane‐1,2‐diamine, were designed, synthesized and spectrally characterized. All the complexes were evaluated for their in vitro cytotoxicity against human HepG‐2, A549, HCT‐116 and MCF‐7 cancer cell lines. The results indicated that all compounds showed positive biological activity against HepG‐2, A549 and HCT‐116 cancer cell lines. In particular, compounds D7 and D2 showed better activity than carboplatin against HepG‐2 and A549 and compound D7 also showed an activity close to that of oxaliplatin. Copyright © 2015 John Wiley & Sons, Ltd.     

Derivatives of 5-nitro-1H-benzo[de]isoquinoline-1,3(2H)-dione: design, synthesis, and biological activity

Abstract  

A series of mono and bis-2-(2-(dimethylamino)-ethyl)-5-nitro-1H-benzo[de]isoquinoline-1,3(2H)-diones with different amino side chains, a novel family of antitumor agents, has been designed and synthesized. Their antitumor activity was evaluated against HeLa, A549, P388, HL-60, MCF-7, HCT-8, and A375 cancer cell lines in vitro. Preliminary results showed that most of the derivatives had antitumor activity comparable with that of mitonafide, with IC ₅₀ values of 10⁻⁶–10⁻⁵ M. More importantly, the derivatives had distinct antitumor selectivity against different cancer cell lines. This work provided a novel class of mitonafide-based lead compounds with improved antitumor selectivity against cancer cell lines for further optimization.     

Convenient synthesis and antitumor evaluation of some new 9-ethyl-3-(hetaryl)carbazoles

Abstract

In continuing our efforts to develop new potent anticancer candidates, a new series of 9-ethylcarbazoles carrying at position 3 various heterocyclic substituents such as 2-imino-2H-chromenes 5a–e, 2-oxo-2H-chromenes 6a–e, 3-imino-3H-benzo[f]chromene 8, 3-oxo-3H-benzo[f]chromene 9, 2-pyridones 11, 14, pyrazole 19, pyrimidine 23, pyrido[1,2-a]pyrimidine 27, 2H-pyran-2-one 30, and pyrano[2,3-d]pyrimidinetrione 34 were efficiently synthesized, characterized and evaluated for their in vitro antitumor activity. The mechanism for the synthesis of compounds was also discussed. Most of the synthesized compounds were displayed the considerable anticancer activities against three human tumor cells lines, in particular, colon carcinoma (HCT-116), hepatocellular carcinoma (HepG-2) and breast cancer (MCF-7). Compound 6d proves as most active molecule in this study with special effectiveness against the human HCT-116 and HepG-2 as its IC₅₀ values are 1.50, 0.90?μM, respectively, when doxorubicin is compared. Compound 34 was also found to have high activity against HepG-2, HCT-116 and moderate activity against MCF-7.     

Design,synthesis and in vitro cytotoxicity of novel dinuclear platinum(II) complexes with a tetradentate carrier ligand

Four novel dinuclear platinum complexes with a tetradentate ligand, (1R,1′R,2R,2′R)‐N¹,N^1′‐(1,2‐phenylenebis(methylene))dicyclohexane‐1,2‐diamine, as the carrier group, have been designed, synthesized and characterized, and their in vitro cytotoxicity against HepG‐2, A549, HCT‐116 and MCF‐7 cell lines evaluated using MTT assay. Results indicate that the targeted dinuclear platinum complexes H1 , H2 , H3 , H4 exhibit significant growth inhibitory properties against HepG‐2, A549 and HCT‐116 cell lines, but none of them show activity against MCF‐7 cell line. Compound H4 shows better antitumor activity than carboplatin against HepG‐2, A549 and HCT‐116 cell lines. Copyright © 2015 John Wiley & Sons, Ltd.