Synthesis of new cyclotriphosphazene derivatives bearing Schiff bases and their thermal and absorbance properties

In this study, a series of cyclotriphosphazene derivatives containing a Schiff base (3a–3d) were synthesized by the reactions of hexachlorocyclotriphosphazene (1) with bis-aryl Schiff bases ( 2a – 2d ) having different terminal groups (H, F, Cl, and Br). The products ( 3a – 3d ) were characterized by elemental and mass analyses, FT-IR, and ¹ H, ¹³ C, and ³¹ P NMR spectroscopies. Furthermore, the structure of compound 3a was also determined by X-ray crystallography. The thermal behaviors and the spectral properties of the new cyclotriphosphazene compounds ( 3a – 3d ) were investigated and the results were compared in the series.     

哌嗪取代查尔酮衍生物的合成及其细胞毒活性

以4-甲氧基苯甲醛与2-溴-4’-氟苯乙酮为原料,经羟醛缩合脱水、取代反应生成4-甲氧基-4’-(1-哌嗪基)查尔酮(2),再通过酰化反应合成了10个新型含哌嗪的查尔酮衍生物,其结构经~1H NMR、~(13)C NMR及HRMS确证。采用MTT法初步测试了目标化合物的体外细胞毒活性,结果表明,化合物3e和4d对肿瘤细胞株Hela和A549均表现出较好的细胞毒活性,可做进一步研究。     

Synthesis,structural characterization and cytotoxic activity of organotin derivatives of indomethacin

The synthesis, characterization and cytotoxic properties in vitro of tri‐n‐butyltin 1‐(4‐chlorobenzoyl)‐5‐methoxy‐2‐methyl‐1H‐indole‐3‐acetate ( 1 ), tri‐phenyltin 1‐(4‐chlorobenzoyl)‐5‐methoxy‐2‐methyl‐1H‐indole‐3‐acetate ( 2 ), tetra‐n‐butyltin[bis‐1‐(4‐chlorobenzoyl)‐5‐methoxy‐2‐methyl‐1H‐indole‐3‐acetato]distannoxane ( 3 ) and di‐n‐butyltin bis‐1‐(4‐chlorobenzoyl)‐5‐methoxy‐2‐methyl‐1H‐indole‐3‐acetate ( 4 ) are described. These compounds have been characterized by ¹H, ¹³C and ¹¹⁹Sn NMR spectroscopy in solution and ¹¹⁹Sn NMR in the solid state, infrared spectroscopy, elemental analysis and X‐ray diffraction for compound 1 . The growth inhibition effects of compounds 1–4 against the lung adenocarcinoma cell line SK‐LU‐1 as well as the cervical cancer cell line HeLa were determined. Compounds 1 and 2 exhibit cytotoxic activity, whereas compounds 3 and 4 are inactive. Copyright © 2008 John Wiley & Sons, Ltd.     

含N-取代哌嗪片段的查尔酮衍生物的合成及其细胞毒活性

以4-甲氧基苯甲醛与2-溴-4’-氟苯乙酮为原料,经缩合、取代反应后,再与α-溴代酮或α-溴代酯反应,合成得到8个查尔酮哌嗪衍生物(3a~3h),其结构经1H NMR、13C NMR和HRMS确证。采用MTT法初步测试了所合成化合物的体外细胞毒活性,结果表明,哌嗪环上含酮基取代的化合物对肿瘤细胞株A549和SGC7901均表现出良好的抑制活性,特别是化合物3a(IC50=0.28μmol/L,2.53μmol/L)活性最高,值得进一步深入研究。     

Marine cytotoxic macrolides haterumalides and biselides, and related natural products

Marine animals and plants are rich sources of bioactive natural products. Haterumalides and biselides, isolated from Okinawan marine animals, are 14-membered macrolides with strong cytotoxicity against human cancer cell lines. This review highlights the isolation, structures, bioactivities, and total synthesis of haterumalides, biselides, and related natural products.     

Synthesis and in vitro cytotoxic activities of sorafenib derivatives

A series of novel sorafenib derivatives have been designed and synthesized.The cytotoxic activities of these compounds were tested in three tumor cell lines.Most of the compounds showed potent antiproliferative activity against the tested cell lines with IC50= 0–20 mmol/L.Some compounds demonstrated competitive antiproliferative activities to sorafenib against all three cancer cell lines.Among them,compound 5g demonstrated significant inhibitory activity against A549,ACHN and MDAMB-231 cell lines with IC50values of 1.29,1.99,3.11 mmol/L,respectively.     

Synthesis,structural characterization,and cytotoxic activity of new spirocyclic octachlorocyclotetraphosphazenes

Octachlorocyclotetraphosphazene, N₄P₄Cl₈, (1) was reacted with N, N′-dibenzylethylenediamine to synthesize partially substituted monospiro- (2), dispiro- (5) and tetraspirocyclotetraphosphazene (8) derivatives. The reactions of 2 and 5 with excess pyrrolidine and morpholine produced fully substituted pyrrolidino (3 and 6) and morpholino (4 and 7) spirocyclotetraphosphazenes. The structures of the compounds were determined with 1D (¹H, ¹³C, ³¹P, and DEPT) NMR, 2D (HSQC) NMR, ESI-MS, FTIR, and elemental analysis. The solid-state structures of 6 and 7 were examined by X-ray crystallography. In 7, intramolecular C-H…O hydrogen bonds link the molecules into centrosymmetric dimmers. The cytotoxic activity of all the compounds against human cervix carcinoma cell lines (HeLa) was investigated. The study showed that these compounds exert limited cytotoxic, apoptotic and necrotic effects on HeLa cancer cell lines.     

The cytotoxic activities of imidazole derivatives prepared from various guanylhydrazone and phenylglyoxal monohydrate

Abstract

A series of imidazole derivatives were synthesized from two-component condensation reaction of phenylgloxal monohydrate with guanylhydrazone. They were characterized by spectroscopic and analytical techniques. The in vitro anticancer evaluation of these compounds was done on human breast cancer (MCF-7) and human liver cancer (HepG2) cell lines using the MTT assay method. Most of the newly synthesized compounds displayed cytotoxic activity against these cancerous cells. In fact, compounds 3a, 3e, and 3?h exhibited more cytotoxic activities than the positive control drugs, fluro-5, and irinocam, against the MCF-7 cell line. Almost all the compounds, except for three, 3b, 3d, and 3f, gave more cytotoxic results than cisplatin. Therefore, these compounds could be considered for further development as anticancer drug candidates.     

Callyptide A,a new cytotoxic peptide from the Red Sea marine sponge Callyspongia species

In the course of our continuing efforts to allocate bioactive secondary metabolites from Red Sea marine invertebrates, we have investigated the sponge Callyspongia species. The cytotoxic dichloromethane fraction of the methanolic extract of the sponge afforded a new cytotoxic peptide named callyptide A (1). Its structure was determined by extensive 1D and 2D NMR (COSY, HSQC and HMBC) studies and high-resolution mass spectral determination. The configuration of the amino acids was determined by Marfey’s analysis. Callyptide A was found to exhibit growth inhibitory activity when tested against different cancer cell lines.     

Isolation and structural modifications of ananixanthone from Calophyllum teysmannii and their cytotoxic activities

Two naturally occurring xanthones, ananixanthone (1) and β-mangostin (2), were isolated using column chromatographic method from the n-hexane and methanol extracts of Calophyllum teysmannii, respectively. The major constituent, ananixanthone (1), was subjected to structural modifications via acetylation, methylation and benzylation yielding four new xanthone derivatives, ananixanthone monoacetate (3), ananixanthone diacetate (4), 5-methoxyananixanthone (5) and 5-O-benzylananixanthone (6). Compound 1 together with its four new derivatives were subjected to MTT assay against three cancer cell lines; SNU-1, K562 and LS174T. The results indicated that the parent compound has greater cytotoxicity capabilities against SNU-1 and K562 cell lines with IC₅₀ values of 8.97 ± 0.11 and 2.96 ± 0.06 μg/mL, respectively. Compound 5 on the other hand exhibited better cytotoxicity against LS174T cell line with an IC₅₀ value of 5.76 ± 1.07 μg/mL.     

Synthesis and cytotoxic activity of novel 4-amino-5-cyano-2-sulfonylpyrimidines

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Synthesis and cytotoxic activity of new annulated furazan derivatives

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Oxadiazole: Synthesis,characterization and biological activities

The synthesis of novel achiral and chiral amides incorporating 1,3,4-oxadiazole ring are reported. All the synthesized amides are characterized ¹H, ¹³C, FTIR and elemental analysis techniques. Synthesized compounds are screened for microbial and cytotoxic activities.     

Synthesis,structural characterization and antimicrobial activities of cyclochlorotriphosphazene derivatives derived from N-(1-Naphthyl)ethylenediamine

Abstract

The nucleophilic substitution reactions of cylochlorotriphosphazene (N₃P₃Cl₆) with N-(1-Naphthyl)ethylenediamine resulted in the following formation of partially and fully substituted cyclotriphosphazene derivatives: 2,4,4,6,6-pentachloro-2-open-chain-N-(1-Naphthyl) ethylendiamino-cyclotriphosphazatriene (3); 4,4,6,6-tetrachloro-2,2-spiro-N-(1-Naphthyl) ethylendiamino-cyclotriphosphazatriene (4); 2,6,6-trichloro-2-open-chain-4,4-spiro-N-(1-Naphthyl)ethylendiamino-cyclotriphosphazatriene (5); 2,4-dichloro-2,4-ansa-6,6-spiro-N-(1-Naphthyl)ethylendiamino)-cyclotriphosphazatriene (6); and 2,4,6-trichloro-2,4,6-non-gem-open-chain-N-(1-Naphthyl)ethylendiamino)-cyclotriphosphazatriene (7); 2,2,4,4,6,6-tri-spiro-N-(1-Naphthyl)ethylendiamino)-cyclotriphosphazatriene (8); 2,4-dichloro-2,4-cis-open-chain-6,6-spiro-N-(1-Naphthyl)ethylendiamino)-cyclotriphosphazatriene (9); and 2,4,6,6-tetrachloro -2,4-ansa-N-(1-Naphthyl)ethylendiamino)-cyclotriphosphazatriene (10). The reactions produced the 4,4,6,6-tetrachloro-2,2-spiro-N-(1-Naphthyl) ethylendiamino-cyclotriphosphazatriene (4) and 2,4,6,6-tetrachloro-2,4-ansa-N-(1-Naphthyl)ethylendiamino)-cyclotriphosphazatriene (10) derivatives as the major products in this system. The structures of the compounds were characterized by FT-IR, elemental analysis, TLC-MS, FT-IR, ¹H, and ³¹P NMR spectral data. All the derived compounds (3–10) were screened for antimicrobial activity by using the broth-agar microdilution technique for the determination of MIC and MCC values. In this context, the compounds were examined against three different human pathogens; Escherichia coli W3110, Staphylococcus aureus ATCC 25923 and Candida albicans ATCC 10231. Except compounds 6 and 9, the rest of the compounds exhibited significant antimicrobial activity on E. coli (W3110), S. aureus (ATCC 25923) and C. albicans (ATCC 1023). Among the synthesized derivatives, compound 4 is the most active agent against the referenced bacteria.     

低聚水溶性壳聚糖修饰阿魏酸及细胞毒活性研究

阿魏酸（Ferulic acid,FA）,化学学名为4-羟基3-甲氧基苯丙烯酸,是当归、川芎、木贼、升麻、樟白皮等中药材水溶性提取物中主要的单体活性成份,属天然酚酸类化合物,由于其优良的抗氧化性,故对一些肿瘤表现出抑制作用,但活性不是很好。另外,由于FA的稳定性差,在人体内不参与肝肠循环等缺陷也影响其药效的发挥。     

Synthesis,antimicrobial, antiquorum-sensing and cytotoxic activities of new series of benzothiazole derivatives

New series of benzothiazole derivatives were designed and synthesized. The newly synthesized compounds were screened for their antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus cereus. Compounds 6j and 6o showed the highest activity against E. coli and S. aureus. The antifungal activity of these compounds was also tested against Candida albicans and Aspergillus fumigatus293. Compounds 4c, 4g and 6j exhibited the highest activity against C. albicans. In addition, compounds4 a and 6j displayed promising activity against A. fumigatus 293. The same compounds were examined for their antiquorum-sensing activity against Chromobacterium violaceum ATCC 12472, whereas compounds4 a, 6j and 6p showed moderate activity. The in vitro cytotoxicity testing of the synthesized compounds was performed against cervical cancer(Hela) and kidney fibroblast cancer(COS-7) cell lines. Results indicated that all tested compounds have IC50 values 50 mmol/L against both cell lines. Molecular properties, toxicities, drug-likeness, and drug score profiles of compounds 4a–c, 5a, 6g,h, 6j, 6l, 6o and7 c,d were also assessed.     

A new aromatic glycoside and its anti-proliferative activities from the leaves of Bergenia purpurascens

Chemical investigation of the ethanolic extracts of the dried leaves of Bergenia purpurascens led to the isolation and identification of a new aromatic glycoside, 1-O-β-D-glucopyranosyl-2-methoxy-3-hydroxyl-phenylethene (1), along with other 19 known compounds (2–20). The structure of compound 1 was determined by a detailed analysis using various analytical techniques, including 1D and 2D NMR. In vitro anti-proliferative activities of compound 1 on five human cancer cell lines were evaluated. The results showed that compound 1 possessed the most potent effects with the IC₅₀ values of 14.36 ± 1.04 μM against T24 cells. The further bioactivity analysis showed that compound 1 induced apoptosis of T24 cells, and altered anti- and pro-apoptotic proteins, leading to mitochondrial dysfunction and activation of caspase-3 for causing cell apoptosis. The present investigation illustrated compound 1 might be used as a potential antitumour chemotherapy candidate.     

Synthesis and antibacterial activities of pleuromutilin derivatives

Six new pleuromutilin derivatives were designed and synthesized, confirmed by MS, IR and 1H NMR techniques. And the antibacterial activities were primarily evaluated in vitro. The results indicated that most of the derivatives showed more potent activities against corresponding bacterial strains than that of pleuromutilin. Especially, compounds 4d and 5b had obvious activities against salmonella compared with pleuromutifin.     

Synthesis, X-ray structural analysis, and cytotoxic activity of some new androstane d-homo lactone derivatives

A series of d-homo lactones 4?C10 from dehydroepiandrosterone 1 via 16-hydroximino derivatives 2 and 3 were synthesized. The d-homo lactone 4 was transformed by the Oppenauer oxidation to obtain compound 5. The (Z)-2-hydroxymethylene-4-en-3-one compound 6, was obtained through reaction of 4-en-3-one compound 5 with ethyl formate and sodium hydride. The epoxides 8 and 9 were prepared from compound 7 by oxidation with m-chloroperbenzoic acid. Compound 10 was obtained by treating epoxides 8 and 9 with chromium(VI)-oxide. The structure of compounds 6 and 10 were confirmed by X-ray structural analysis. These derivatives were screened for antitumor activity against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7, human breast adenocarcinoma ER?, MDA-MB-231, prostate cancer AR?, PC-3), and one human non-tumor cell line, MRC-5. Compounds 4, 7, 8, and 10 exhibited significant antitumor activity against MDA-MB-231 cells, while compound 5 showed strong cytotoxicity against MDA-MB-231. No compounds displayed toxicity against MRC-5 cells.