Acridine derivatives. IV. Synthesis,molecular structure,and antitumor activity of the novel 9-anilino-2,3-methylenedioxyacridines

In the biological and physical investigation of a new class of deoxyribonucleic acid (DNA)-intercalating antitumor agents, novel 9-anilino-2,3-methylenedioxyacridines (twelve compounds) have been synthesized and evaluated for the activity against L1210 leukemia in vivo. A few of them possessed the same potency of the antitumor activity as 4′-(9-acridinylamino)methanesulfonyl-m-anisidine (amsacrine, m-AMSA), which is an important antitumor agent in clinical use. The molecular structure of a typical one, 9a in this series have been determined by the X-ray diffraction method using a single crystal. The results of this X-ray investigation have shown that the new class of acridine derivatives have the methylenedioxy group fused at the 2- and 3-positions of the acridine ring.     

Design,synthesis and insecticidal activities of novel 1-substituted-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives

A series of novel 5-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives(6a–6n, 7a, 7b, and 8a-8f)were synthesised by placing the amide bond at the 4-position of the pyrazole ring. These derivatives differed from the structure of chlorantraniliprole analogues with the amide bond at the 5-position of the pyrazole ring. Preliminary bioassay results revealed that a few title compounds exhibited good insecticidal activities against lepidopteran pests, such as Plutella xylostella, Mythimna separate, Heliothis armigera, and Ostrinia nubilalis. Some title compounds also elicited broad-spectrum insecticidal activities against dipterous insects including Culex pipiens pallens after altering the amide position. Similar to pyrazole-5-carboxamide analogues, compounds 6b and 6e showed 100% insecticidal activity against P. xylostella, C. pipiens pallens, and M. separate at concentrations of 200, 2, and 200 mg/m L, respectively.This finding suggested that 5-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives are potential alternative insecticides for management of agriculture pests.     

吲哚-6-酰腙类化合物的微波合成及其抗菌活性研究

把酰腙类结构引入吲哚环中, 合成一类新型的吲哚-6-酰腙化合物, 以期为新药筛选提供先导化合物. 在微波辐射条件下, 以较高的产率得到14个未见报道的新化合物, 其结构均经1H NMR, IR, MS及元素分析确证, 并测试了化合物的抑菌活性.     

10-甲基吖啶苯酚酯衍生物的合成、表征及化学发光特性

吖啶-9-羧酸苯酚酯是一类效率较高的化学发光试剂.其结构一般有两部分组成,吖啶环发光部分和9-羧酸苯酚酯离去基团.本文对离去基团进行修饰,分别在离去基团苯酚部分的2,5或2,6位引入取代基CF₃、NO₂、Br、CH₃,合成了4个新吖啶酯衍生物,并对它们的分子结构进行了表征.4个新化合物和模型化合物(无取代基)比较,均表现出较好的化学发光效率;发光动力学基本符合文献报道规律.而且化学发光法对其水解稳定性考察显示,取代基的电性和位阻是影响稳定性的两大因素.     

Velutabularins A-J, phragmalin-type limonoids with novel cyclic moiety from Chukrasia tabularis var. velutina

Velutabularins A-J, ten novel phragmalin-type limonoids, were isolated from the stem bark of Chukrasia tabularis var. velutina. In structures of 1-6, the tetrahydrofuran ring from dehydration of OH-15 and OH-17, ring C and 13/14/18-cyclopropanyl moiety formed an unprecedented 8-oxatricyclo[4,3,1^1,6]decane. Compounds 7-10 are derivates of 1-6 opening the tetrahydrofuran ring. All of these compounds possess a novel C-16/C-30 δ-lactone ring, which were reported in phragmalins rarely. The structures of these novel compounds were elucidated based on extensive 1D and 2D spectroscopic analysis. The absolute configuration of 5 and 9 were determined by the calculated electronic circular dichroism (ECD) method. The anti-inflammatory activities of major compounds (2, 4, 5, 9) were evaluated for inhibitory activity against lipopolysaccharide (LPS) induced nitric oxide (NO) production in macrophage (RAW264.7) cell line.     

N-(5-芳苄叉基饶丹宁)左氧氟沙星酰胺的合成及抗肿瘤活性

为进一步发现氟喹诺酮药物向抗肿瘤活性转化的结构修饰新策略,用酰氨基为左氧氟沙星(1)C-3羧基的电子等排体,5-芳苄叉基饶丹宁为其功能修饰基,设计合成了N-(5-芳苄叉基饶丹宁)左氧氟沙星酰胺类目标化合物(6a-6n)。 体外抗肿瘤活性结果表明,所合成的14个化合物的活性均强于母体左氧氟沙星,且对正常细胞表现出较低的细胞毒性作用。 构效关系表明,增大芳基取代基的体积或供电性均导致抗肿瘤活性的明显降低,反之,吸电子取代苯基或芳香杂环类目标化合物的抗肿瘤活性强于其他取代基类。 其中,硝基化合物6l、呋喃6m和吡啶6n对人胰腺癌细胞株(Capan-1)的半数抑制浓度(IC₅₀) 与对照抗肿瘤药阿霉素(1.6 μmol/L)相当,分别为1.8、0.8和1.3 μmol/L。 因此,芳苄叉基饶丹宁修饰的酰氨基替代C-3羧基有利于提高氟喹诺酮的抗肿瘤活性。     

Isoquino[4,5-bc]acridines: design, synthesis and evaluation of DNA binding, anti-tumor and DNA photo-damaging ability

Several novel isoquino[4,5-bc]acridine derivatives have been designed and synthesized. Their DNA-binding, anti-tumor and DNA-photo-damaging properties were investigated. A4 exhibited the highest anti-tumor activities against both A 549 (human lung cancer cell) and P388 (murine leukemia cells). All these compounds were found to be more cytotoxic against P388 than against A549. Under 365-nm light irradiation, A3 damaged plasmid DNA pBR322 at <2 microM and cleaved DNA from form I to 100% form II by 50 microM. The mechanism studies revealed that A3 damaged DNA by electron transfer mechanism and singlet oxygen species.     

Synthesis and Tumor Cytotoxicity of Novel 1, 2, 3-Triazole-substituted 3-Oxo-oleanolic Acid Derivatives

Fifteen novel 3-oxo-oleanolic acid esters bearing aryl substituted 1,2,3-triazolyl methyl moiety were synthesized via the method of Copper(I)-catalyzed Huisgen cycloaddition. The cytotoxicity evaluation results of these compounds against five human tumor cell lines show that most of these compounds presented potent activity and selectivity against A375-S2 and HT1080 cells. Compound 6c, with a p-NO₂ at the bezene ring, possesses the best inhibitory activity against A375-S2(IC₅₀=2.82 μmol/L) and HT1080(IC₅₀=1.69 μmol/L).     

Synthesis and antitumor activities of novel benzoylphenylurea derivatives.

Seventy novel benzoylphenylurea compounds were synthesized and their antitumor activities were examined in vivo against P388 leukemia. N-(2-Nitrobenzoyl)-N'-[4-(2-pyrimidinyloxy)phenyl]ureas showed the highest antitumor activities when dosed intraperitoneally or orally. Their structure-activity relationships were examined with particular focus on the position and the variety of substituent on each aryl ring.     

新型含噻唑和三唑环的亚胺类化合物的合成及生物活性研究

设计合成了一系列新型含有噻唑和三唑环的亚胺类化合物, 其结构经元素分析、1H NMR和X射线晶体衍射确证. 生物活性测试结果表明, 部分化合物在50 μg/L浓度下对苹果轮纹菌具有一定的杀菌活性.     

Syntheses of Lactam Derivatives of Chenodeoxycholic Acid and in vitro Antiproliferative Activity

With chenodeoxycholic acid as starting material,a series of lactam derivatives of chenodeoxycholic acid was synthesized and their antiproliferative activities against some cancer cells were determined.Among the synthesized derivatives,compounds 6 and 18 displayed distinct antiproliferative activity against PC-3,H-292,SKBR3 and Hey-1B cancer cells,and compounds 10,17 and 18 showed significant antiproliferative activity against SKBR3 cells.Our results reveal that the position of hydroximino on ring A or B of the parental scaffold dramatically affects the antiproliferative activity of these compounds.The conversion of 7-hydroximino to other substituent or 7-hydroximino to 3-hydroximino in the compounds resulted in a dramatic decrease of the antiproliferative activity,suggesting the importance of 7-hydroximino group for the biological activity of the compounds.The structure/activity correlation generated from the studies provides valuable information for the further design of novel chemotherapeutic drugs.     

Syntheses of 2- or 6-Substituted Chromones and Chromone Ring-opening Reaction in Polyphosphoric Acid

In an attempt to find new antitumor agents, a novel class of chromone compounds with a benzimidazoleor a benzoxazole ring in positions 2 or 6 were synthesized νia condensation in polyphosphoric acid(PPA) byusing chromone acids as the starting materials. During the preparation process, it was found that PPA couldcleave the chromone ring to produce a ring-opening compound(6). The molar ratio of the chromone com-pound (5) to the ring-opening compound (6) varied with the change of reaction temperature and time. Basedon MTT protocol, the antitumor activity of each of the compounds obtained was evaluated against three hu-man cancer cell lines: KB(oral epidermal), A2780(ovary) and Be17402 (liver). The IC50 varied from 54.7μmol/L to more than 180 μmol/L.     

Synthesis and Biological Activities of Novel 1,2,4-Triazole Derivatives Containing 1,2,3-Thiadiazole Ring

A series of novel 1,2,4-triazole derivatives containing 1,2,3-thiadiazole ring was designed and synthesized. Their structures were confirmed by IR, 1^H NMR, high resolution mass spectrometer（HRMS） and electrospray ionization-mass spectromcter（ESI-MS） combined with melting points and elemental analysis. Preliminary bioassays indi- cate that these compounds exhibit good insecticidal activity against Aphis laburni at 100 μg/mL, especially compound 6b shows mortality of no less than 95%. Most of the compounds show good activities against tobacco mosaic virus（TMV） with different modes in vivo at 100 μg/mL. Compound 6d standed out, showing a good insecticidal activity and very high induction effects against TMV in vivo. Collectively, our data demonstrate a new strategy for insect and virus control.     

An efficient one pot I2/DMSO mediated synthesis and molecular modeling of novel fused pyrimidine-chromone hybrids bearing potential antibacterial and antifungal pharmacophores sites

A series of novel ethyl-l, 1, 2, 3, 6-tetrahydro-4-methyl-1-(6-methyl-4-oxo-4H-chromene-2-yl)-2-oxo/thioxo-6-phenyl pyrimidine-5-carboxylate compounds ( 2a–2k ) were synthesized using I₂/DMSO as a competent and cost-effective catalyst in one pot green solvent system from corresponding chalcones ( 1a–1k ) in better yields. IR, ¹H-NMR, ¹³C-NMR, Mass, and X-ray diffraction spectroscopic techniques were used for the characterization of newly synthesized compounds. All the compounds were tested for in-vitro antibacterial activities against gram-positive and gram-negative bacteria like Staphylococcus aureus, Salmonella abony, Staphylococcus epidermidis, and Escherichia coli. Antifungal activities were also performed against Candida albicans and Aspergilus niger. It was found that the presence of electron withdrawing group on the aromatic ring attached to chromone ring increases the antibacterial activities ( 2g , 2h , and 2k ); while the presence of electron releasing groups decreases activities. The presence of electron donating groups (─OCH₃, ─Cl), on the phenyl ring attached to pyrimidine skeleton influenced negatively for the antibacterial activities.     

溴代甲氧基二苯甲酮咪唑类化合物的合成及对过氧化氢致EA. hy 926细胞损伤的保护作用

本文旨在引入咪唑环,对溴代甲氧基二苯甲酮类化合物进行结构衍生,以发现对血管内皮细胞具有更高保护活性的化合物。通过以2-甲基-5-溴-苯甲酸为起始原料,经过酰氯化、傅克酰化、溴代、与N-溴代丁二酰亚胺(NBS)自由基取代及与取代咪唑的亲核取代等多步反应,合成了8个新型溴代甲氧基二苯甲酮咪唑类化合物。目标化合物的结构均经质谱(MS)、核磁共振波谱仪(NMR)和高分辨质谱(HRMS)进行确证。并采用噻唑蓝(MTT)法考察了目标化合物对过氧化氢损伤的EA.hy 926细胞的保护活性,结果表明,目标化合物6a、6g、6h具有显著的细胞保护活性,其半抑制浓度(EC50)分别为1.9、4.0和3.2μmol/L,优于阳性对照槲皮素(EC_(50)为18μmol/L),表明该类化合物在心血管疾病的治疗方面有潜在的应用前景。     

Efficient Synthesis of New 2H‐Chromene Retinoids Hybrid Derivatives by Suzuki Cross‐coupling Reactions

In an attempt to improve anticancer activity, a series of retinoids–chromene hybrids was described. The novel heterocyclic chromene–retinoids hybrid including oxygen as a heteroatom in a six‐membered cyclic ring (2H‐chromene or 2H‐1‐benzopyran) was designed and synthesized by introducing different groups such as an aromatic or styrylphenyl ring in 6‐position of 2H‐chromene. These novel compounds were synthesized by using the efficient cascades one‐pot process involving Wittig–Horner–Emmons reaction and Suzuki–Miyaura cross‐coupling pallado‐catalyzed reactions with 60% to 90% overall yields. These new compounds were tested against glioblastoma multiforme brain cancer, medulloblastoma, neuroblastoma cell lines, and breast cancer MCF‐7 cell lines. Two of them exhibited an appreciable anti‐tumor activity in the low micromolar range, which opens new perspectives for therapeutic application on humans.     

Study on the synthesis and antimicrobial activity of novel cationic porphyrins

A novel series of quaternary ammonium cationic derivatives based on tetrapyridyl-porphyrin was synthesized.All the compounds were evaluated for their in vitro antibacterial activities against S.aureus,E.coli and P.aeruginosa,and antifungal activities against C.albicans,where microorganisms were exposed and unexposed to the irradiation.The results revealed that some of these compounds,especially,3a and 4a displayed satisfactory antibacterial activity against Gram-positive bacteria S.aureus and moderate an...     

Mono-, and dibenzacridine imines. Synthesis of 1a,11b- dihydrobenz[c]azirino[α]acridine, 4b,5a-dihydrodibenz[c,h]- azirino[α]acridine and 1a,13b-dihydrodibenz[c,j]azirino[α]acridine

The syntheses of the K-imine derivatives of benz[c]acridine, dibenz[c,h]acridine and dibenz[a,h]acridine are described. The parent hydrocarbons 1, 6 and 11 were oxidized with sodium hypochlorite under phase transfer conditions to the corresponding K-oxides 4,9 and 14 , which in turn were reacted with sodium azide. The resulting azido alcohols were then cyclized with tributylphosphine to the title compounds 5,10 and 15.     

Guanidiniocarbonylpyrrole–Aryl Derivatives: Structure Tuning for Spectrophotometric Recognition of Specific DNA and RNA Sequences and for Antiproliferative Activity

We present a systematic study of different guanidiniocarbonylpyrrole‐aryl derivatives designed to interact with DNA or RNA both through intercalation of an aromatic moiety into the base stack of the nucleotide and through groove binding of a guanidiniocarbonylpyrrole cation. We varied 1) the size of the aromatic ring (benzene, naphthalene, pyrene and acridine), 2) the length and flexibility of the linker connecting the two binding groups, and 3) the total number of positive charges present at different pH values. The compounds and their interactions with DNA and RNA were studied by UV/Vis, fluorescence and CD spectroscopy. Antiproliferative activities against human tumour cell lines were also determined. Our studies show that efficient interaction with, for example, DNA requires a significantly large aromatic ring (pyrene) connected through a flexible linker to the pyrrole moiety. However, a positive charge, as in 12 , is also needed. Compound 12 allows for base‐pair‐selective recognition of ds‐DNA at physiological pH values. The antiproliferative activities of these compounds correlate with their binding affinities towards DNA, suggesting that their biological effects are most probably due to DNA binding.     

Hetarylation of pyrazolones by salts of N-acylheteroaromatic cations

Isoquinoline, acridine, benzimidazole, and benzoxazole residues were introduced into the pyrazolone ring by reaction of N-heteroaromatic compounds with pyrazolones in the presence of acylating agents.See [1] for our preliminary communication [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1394–1397, October, 1977.