A contribution to the study of the modified Marschalk reaction: Hydroxymethylation of 6,8-O-dimethyl emodin

<正>Hydroxymethylation of 6,8-O-dimethyl emodin was easily achieved in good yields by the modified Marschalk reaction.The influence of the amount of solvent,base and formaldehyde toward the hydroxymethylation was discussed.The results showed that a relatively dilute reaction solution facilitated the generation of the desired 2-hydromethyl product,while the thick reaction solution benefited the generation of the methylated quinizarins.     

Synthesis and antitumor activity of N1-acetylamino-(5-alkyl/aryl-1,3,4-thiadiazole-2-y1)-5-fluorouracil derivatives

A new series of N1-acetylamino-(5-alkyl/aryl- 1,3,4-thiadiazole-2-y1)-5-fluorouracil derivatives were designed and synthesized.These compounds have not been reported in literature,and their structure chemical were confirmed by IR,1H NMR and MS (HRMS).The results of antitumor inhibitory activity test showed that some compounds possess more potent antitumor inhibitory activity than 5-fluorouracil.     

氨基酸5—氟尿嘧啶酯类衍生物的合成及其抗肿瘤活性研究

用氨基酸作抗癌药物载体以提高对癌细胞选择性的研究引起了人们的浓厚兴趣。在前文中,我们报道了5-氟尿嘧啶乙酰和丙酰氨基酸及其氨基酸的3-(N′-5-氟尿嘧啶基)-丙醇酯的合成及其抗肿瘤试验研究。本文将报道一系列氨基酸(5-氟尿嘧啶-1,3-双丙基)酯盐酸盐的合成及其体外抗肿瘤活性的研究。 合成路线如下:     

A synthesis of emodin anthrone

Summary A novel high yield (74% overall) synthesis of five steps to prepare emodin anthrone, which serves as a valuable precursor of hypericin, was devised using the benzamideortho lithiation strategy for the key step.Dedicated to Prof. K. Schaffner on the occasion of his 60th birthday     

Synthesis and antibacterial activity of emodin and its derivatives against methicillin-resistant Staphylococcus aureus

Synthesis of the antibacterial emodin was improved using Friedel-Crafts acylation as a key step leading to 37% overall yield. In addition, 21 analogues were synthesized by structural modification of the hydroxyl and methyl groups, as well as the aromatic ring of emodin. Antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and cytotoxicity against noncancerous Vero cells were evaluated. A structure-activity relationship (SAR) study indicated that the hydroxyl groups and the methyl group in the emodin skeleton were crucial for anti-MRSA activity. Furthermore, the presence of an iodine atom or ethylamino group on the aromatic ring enhanced the anti-MRSA activity with higher selectivity indices, while derivatives containing bromine, chlorine atoms or quaternary ammonium salt were as active as emodin. The quaternary ammonium group on the aromatic ring also led to non-cytotoxicity against Vero cells.     

Synthesis and antitumor activity of N^1-acetylamino-（5-alkyl/aryl-1,3,4-thiadiazole-2-yl）-5-fluorouracil derivatives

A new series of N^1-acetylamino-（5-alkyl/aryl- 1,3,4-thiadiazole-2-yl）-5-fluorouracil derivatives were designed and synthesized. These compounds have not been reported in literature, and their structure chemical were confirmed by IR, ^1H NMR and MS （HRMS）. The results of antitumor inhibitory activity test showed that some compounds possess more potent antitumor inhibitory activity than 5-fluorouracil.     

氨基酸5-氟尿嘧啶酯类衍生物的合成及其抗肿瘤活性研究

以N-保护的氨基酸钾盐与1-(ω-溴丙基)-5-氟尿嘧啶和1-(ω-溴丁基)-5-氟尿嘧啶反应,制备了18种氨基酸的ω-(N¹-5-氟尿嘧啶基)-丙醇酯和丁醇酯的盐酸盐,并确定了它们的结构。动物试验的初步结果表明,酪氨酸、苯丙氨酸的3-(N¹-5-氟尿嘧啶基)-丙醇酯盐酸盐对小鼠艾氏腹水癌的抑制率分别为88.1%和86.7%。     

短肽5－氟尿嘧啶前体药物的合成及其抗肿瘤活性研究

短肽５－氟尿嘧啶前体药物的合成及其抗肿瘤活性研究罗毅,卓仁禧,范昌烈（武汉大学化学系,武汉,４３００７２）关键词氨基酸,短肽,５－氟尿嘧啶,抗肿瘤活性５－氟尿嘧啶（５－ＦＵ）是一种治疗癌症的广谱性抗代谢药物,但由于其毒副作用较大,从而限制了它在临床上...     

5-氟尿嘧啶N1-甲酰基氨基酸、短肽的合成及抗肿瘤活性

5-氟尿嘧啶N¹-甲酰氯分别与Gly、Val、Leu、Ile、Phe、Asp和Glu的苄酯反应,制备了7种5-氟尿嘧啶-N¹-甲酰基氨基酸苄酯。氢解后得到了相应的5-氟尿嘧啶N¹-甲酰氨基酸。将其进一步与氨基酸甲酯或二肽甲酯缩合,制备了5-氟尿嘧啶N¹-甲酰基二肽甲酯和三肽甲酯。5-氟尿嘧啶-N¹-甲酰基二肽甲酯也可采用5-氟尿嘧啶-N¹-甲酰氯与二肽甲酯直接反应制备。     

Synthesis and Biological Evaluation of Novel Uracil and 5-Fluorouracil-1-yl Acetic Acid-Colchicine Conjugate

A series of novel uracil and 5-fluorouracil-1-yl-acetic acid-colchicine derivatives(6a-6n) was synthesized via coupling uracil and 5-fluorouracil(5-FU) with C-10 analogues of colchicine. The antitumor activities of the target compounds against human hepatocellular carcinoma(BEL7402) cells, human ovary carcinoma(A2780) cells, human lung adenocarcinoma(A549) cells and human breast carcinoma(MCF7) cells were tested in vitro, and the structure-activity relationship(SAR) of the compounds was also studied. The bioassay results demonstrate that most of the tested compounds display significant activity and particularly, compounds 6a, 6e, 6h and 6l show more potent cytotoxic activities than 5-fluorouracil and colchicine. The results show that the new derivatives of colchicine are potential suppressors on human cancer.     

含5-氟尿嘧啶生物可降解聚磷酰胺的合成及其抗肿瘤活性研究

通过L-赖氨酸(N¹-5-氟尿嘧啶)烷基酯双盐酸盐与二氯磷酸乙酯、二氯膦甲酸乙酯、二氯膦乙酸乙酯共聚,合成了三类12种侧链含5-氟尿嘧啶的聚磷酰胺。聚合物的结构经UV、IR、¹H NMR及元素分析鉴定。聚合物用微量细胞培养四氮唑实验方法(MTT法)进行了对人肝癌细胞系Bel-7402细胞的微量培养实验。     

Synthesis and Antitumor Activity of Poly-L-Lysine Containing 5-Fluorouracil as Pendent Group

Homopolymers of L-amino acids such as poly(L-glutamic acid) and poly (Llysine) not only have good biocompatibility and biodegradability, but also lack of immunogenicity. It has been reported that homopoly(L-amino acids) were used as the carriers of antitumor drugs such as mustard, methotrexate (MTX), cyclophosphamide, daunomycin(DM) and adriamycin (ADR). 5-Fluorouracil(5-FU) is most useful for the treatment of patients with carcinoma of the breast and gastrointestinal     

Synthesis,physico-chemical studies and biological evaluation of new metal complexes with some pyrazolone derivatives

A series of N-substituted-4-thiocarbamoyl-5-pyrazolone derivatives (HL¹-HL⁴) is presented as chelating agents for complexation with Fe(III), Ni(II) and Cu(II) metal ions. The synthesized pyrazolone ligands and their newly metal complexes are characterized by different spectral and analytical methods such as UV–Vis, IR, ¹H NMR, ¹³C NMR, ESR, MS, magnetic measurement, and TGA. The spectral data reveal that ligands coordinated to metal ions in a bidentate pattern via O & N atoms of the OH group at C(5) and thiocarbamoyl (–CSNHR) at C(4) of the pyrazolone ring. Also, the analytical data suggest the stoichiometries 2:3 (M:L) for both Cu(II) & Ni(II) complexes and 1:3 for Fe(III) complexes. Besides, the normal magnetic moments values for Fe(III) complexes confirm high spin octahedral structure while the diamagnetic nature of all Ni(II) complexes is consistent with square planar geometry. However, the subnormal magnetic values for Cu(II) complexes suggest the proposal of their binuclear structures. The ESR spectra of the Cu(II) complexes support the distorted square planar geometry with a considerably strong intradimeric spin-exchange interaction. Moreover, the anticancer, antibacterial and antifungal activities are screened. Among the synthesized compounds, HL⁴ ligand exhibits a significant broad spectrum of action against Gram-positive (S. aureus), Gram-negative bacteria (P. vulgaris), and antifungal potency against A. fumigatus & C. albicans in comparison with gentamicin and ketoconazole drug. Such potency of HL⁴ could be related to the insertion of the p-chloro in the phenyl group attached to the pharmacophoric thiocarbamoyl group at C(4). Furthermore, IC₅₀ values of two Cu(II) complexes derived from HL² and HL³ display nearly twofold or threefold more cytotoxicity impact against three cell lines (MCF-7, HCT116 and HepG-2) compared with cis-platin as positive control.     

1-芳磺酰基-3-N-(β-D-乙酰基吡喃半乳糖-1-基)-5-氟脲嘧啶的合成和表征

在相转移催化条件下,２,３,４,６－四－Ｏ－乙酰基－１－溴－１－脱氧α－Ｄ－吡喃半乳糖与１－芳磺酰基－５－氟脲嘧啶反应合成了７个新的１－芳磺酰基－３－Ｎ－（β－Ｄ－乙酰基吡喃半乳糖－１－基）－５氟脲嘧啶类化合物,其结构经元素分析,ＩＲ及＾１ＨＮＭＲ证实。     

Synthesis and antiviral activities of novel 1,4-pentadien-3-one derivatives bearing an emodin moiety

A series of 1,5-diaryl-1,4-pentadien-3-one derivatives bearing an emodin group were designed and synthesized by the combination of natural products. The antiviral activities against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) in vivo were evaluated. Some of the derivatives displayed promising curative effect and protective activity against TMV. Compound D5 showed appreciable curative bioactivity on TMV approximately of 50% at 306.2 mg/mL, which was superior to ningnanmycin (409.3 mg/mL).     

A new series of mesogenic pyran derivatives

4-[4-(3,6-Dihydro-4-methyl-2H-pyran-3-ylhydroxy)phenylaminocarbonylmethoxy]benzylidene-4-alkoxyanilines, which have the properties of smectic and nematic liquid crystals, were synthesized.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1628–1630, December, 1993.     

高分子药物研究——ⅩⅦ. 二羟烷基嘧啶与N,N’-双(2-氯乙基) 二氯磷酰胺缩聚物的合成及其抗肿瘤活性研究

本文通过七种二羟烷基嘧啶单体与N,N’一双(2-氯乙基)氯磷酰胺进行缩聚反应,制得了七种新的含核酸碱基或其类似物和氮芥的聚磷酸酯,用核磁、红外光谱及元素分析确定了单体和聚合物的结构。部分聚合物试验结果表明,既含氮芥又含5-氟尿嘧啶的聚合物具有较高的抗癌活性和较低的毒性,聚合物(Ⅲ_a)对小鼠艾氏腹水癌的抑制率可达66％。     

侧链含5-氟尿嘧啶甲壳胺的合成及其抗肿瘤活性的研究

本文报道了以不同分子量的甲壳胺为载体,制备了侧链含5-氟尿嘧啶的一系列高分子载体药物;通过定氮分析测定了H_2N-基的反应率;由IR、UV和~(13)C-NMR确定了载体药物的结构;模拟生理条件考查了在不同pH的缓冲溶液中5-氟脲嘧啶或其衍生物的水解释放率。体外初步实验结果表明,具有Ⅰ和Ⅱ结构的载体药物对艾氏腹水癌细胞有较强的杀伤作用。     

Anticancer potential of novel 5-Fluorouracil co-crystals against MCF7 breast and SW480 colon cancer cell lines along with docking studies

In the present investigation, 5-Fluorouracil co-crystals with four cyclic dimers of amino acids (Glycine, Tryptophane, Leucine and Alanine conformers are prepared via co-crystallization route, with an aim to improve its anticancer effectiveness and to minimize its associated drawbacks. The prepared co-crystals were characterized by FTIR and PXRD techniques. FTIR revealed the presence of respective functional groups in the prepared co-crystals. Frequencies (v) of NH (3416 cm^?1) and carbonyl group (1671 cm^?1) in the 5-Fu (FTIR) spectrum were considerably moved in all co-crystal’s spectra exhibiting the development of new interactions. 5-Fu peak at 2θ = 28.48° was visibly transformed in the co-crystal’s graphs of PXRD. MTT assays was studied on MCF7 breast and SW480 colon cancer cell lines using 0.78 to 200 μg mL^?1 dose concentration. Co-crystals with Tryptophane and Leucine cyclic dimers revealed highest potential (99 % and 100 %) respectively, against colon cancer cell line Likewise Alanine and Tryptophane dimers furnished promising efficiency (100 %) against MCF7 cell line Genetic Optimization for Ligand Docking/GOLD was applied to evaluate the latent anti-tumor behaviors against the proteins [C-myc. (PDB ID: 6G6K, Thymidylate synthase (PDB ID:1HVY) and protein kinase (PDB ID: 2X18). Results revealed that the developed 5-Fluorouracil co-crystals have promising antitumor efficacy as compared to already reported 5-Fu co-crystals and 5-Fu alone.     

A new series of mesogenic derivatives of pyrimidine-substituted

Analogs of known mesogenic 2,5-diarylpyrimidines, 5-[p-alkyl(alkoxy)phenyl]-2-(o-hydroxy-p-alkoxyphenyl)pyrimidines (I), have been synthesized that have a wider mesogenic phase temperature range. Pyrimidines I show smectic C and A phases but not the nematic phase.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 377–381, March, 1992.