Synthesis,cytotoxic activity,and fluorescence properties of a set of novel 3-hydroxyquinolin-4(1H)-ones

The targeted solid-phase synthesis of 3-hydroxyquinolin-4(1H)-one derivatives is described. Primary and secondary amines, 3-amino-4-(methoxycarbonyl)benzoic acid and 2-bromo-1-(4-chloro-3-nitrophenyl)ethanone were used as starting materials. The structures of the final compounds were designed in accordance with previous information obtained from structure–activity relationship studies of similar cytotoxic derivatives. Representative prepared compounds were subjected to in vitro screening of cytotoxic activity against various cancer cell lines; the results obtained are discussed. Fluorescence properties of selected compounds were also studied to compare the data with those obtained in analogous derivatives.     

Solid-phase synthesis of cyclic hexapeptides wollamides A,B and desotamide B

Solid-phase synthesis of antibacterial cyclohexapeptides including wollamides A, B and desotamide B has been developed. Briefly, the protected linear hexapeptides were assembled on 2-chlorotrityl chloride resin using standard Fmoc chemistry and diisopropylcarbodiimide/hydroxybenzotriazole coupling reagents, cleaved off-resin with hexafluoroisopropanol/dichloromethane to keep side-chain protecting groups intact, and cyclized in solution. Final global removal of all protecting groups using a cocktail of trifluoroacetic acid/triisopropylsilane/dichloromethane afforded the desired cyclic hexapeptides, which were characterized by ¹H, ¹³C NMR, and HRMS. Subsequent investigation of macrocyclization parameters such as terminal residues, coupling reagents, and cyclization concentration revealed the optimized conditions for the synthesis of this class of cyclic hexapeptides.     

Synthesis of new diverse macrocycles from diol precursors

The formation of a library of diverse macrocycles with different ring sizes from two easily accessible building blocks is presented. Reacting diol precursors with electrophilic reagents lead to 17-membered sulfites and 19-membered malonates in 34-79% yield. Double-reductive amination of dialdehyde analogs of the diol precursors leads to 15-membered amines in yields ranging from 9 to 60%, reflecting large differences in reactivity based on steric environment.     

液相法制备具有双尺寸粗糙度的超疏水铜表面

基于简单的液相法,以硫代硫酸钠和氯化铜为原料在铜片表面上构筑了具有微/纳米双尺寸粗糙度的硫化铜膜.用X射线衍射(XRD)仪、扫描电镜(SEM)、能量色散X射线(EDX)光谱仪及光学视频接触角仪对处理前后的铜表面进行了表征和分析.处理后的超亲水铜表面经硬脂酸修饰后具有超疏水效应,静态接触角高达161°,5μL水滴滚动角低至2.5°左右.超疏水性能归因于表面具有双尺寸粗糙度和低表面能的硬脂酸.该方法简单,无需复杂制备过程和苛刻设备,所得超疏水铜表面具有优异的不粘附性、长时间储存的稳定性和一定的耐摩擦性能.     

The First Total Synthesis of Preverecynarmin

Preverecynarmin, isolated from a pennatulacean coral, has been synthesized from E,E-farnesol. The key steps are alkylation of the cyanohydrin trimethylsilyl ether 5 with the halide 6 , the regioselective epoxidation of the siloxyl ether 9 , and the intramolecular macrocyclization of the siloxyl ether 12 induced by Ti(0).     

Synthesis and cytotoxic evaluation of new colchicine derivatives bearing 1, 3, 4-thiadiazole moieties

In search of novel anticancer agents, a series of N-methyl colchiceinamide derivatives (7a-7i) containing 1,3,4-thiadiazole moieties were synthesized, and their structures were confirmed by spectral analysis. Cytotoxicity of these compounds was evaluated by MTT assay in vitro against four human tumor cell lines, i.e. A2780, A549, BEL7402, and MCF-7. The results indicated that most of the derivatives showed significant anticancer activities, particularly, compounds 7h and 7i showed more potent cytotoxic activities of all screened cancer cells than colchicine.     

Synthesis,characterization, antitumor,and cytotoxic activity of mononuclear Ru(II) complexes

In the search for antitumor active metal complexes several ruthenium complexes have been reported to be promising. A series of mononuclear Ru(II) complexes, [Ru(T)₂(S)]²⁺, where T?=?2,2′-bipyridine/1,10-phenanthroline and S?=?CH₃-bitsz, Cl-bitsz, Br-bitsz, tmtsz, dmtsz, have been prepared and characterized by UV-Vis, IR, ¹H-NMR, FAB-mass spectroscopy, and elemental analysis. The complexes were subjected to in vivo anticancer activity against a transplantable murine tumor cell line Ehrlich's ascitic carcinoma (EAC) and in vitro cytotoxic activity against human cancer cell line Molt 4/C₈, CEM, and murine tumor cell line L1210. Ruthenium complexes showed promising biological activity especially in decreasing tumor volume and viable ascitic cell counts. Treatment with these complexes prolonged the life span of EAC-tumor-bearing mice by 10–48%. In vitro evaluation of these ruthenium complexes revealed cytotoxic activity from 0.21 to 24?µmol?L^?1 against Molt 4/C₈, 0.16–19?µmol?L^?1 against CEM, and 0.75–32?µmol?L^?1 against L1210 cell proliferation, depending on the nature of the compound.     

First Total Synthesis of 1,2-Dehydronephthenol

The first total synthesis of 1,2-Dehydronephthenol (15-hydroxy-cembra-1,3,7,11-tetraene), a novel cembranoid diterpene, was accomplished starting from trans, trans-farnesol through seven steps in an overall yield of 17% by employing titanium-induced intramolecular keto aldehyde reductive olefination-coupling as the key macrocyclization step.     

Synthesis,structure, urease inhibitory,and cytotoxic activities of two complexes with protocatechuic acid derivative and phenanthroline

Two complexes, [Cu^II(L¹)(phen)₂](ClO₄) (1) and [Ni^II₂(L¹)₂(phen)₂(MeOH)₂](ClO₄)₂ (2), with HL¹, a ligand derived from protocatechuic acid (=2,3-dihydrobenzo[b][1,4]dioxine-6-carboxylic acid) and phen (=1,10-phenanthroline) were synthesized and characterized by C, H, and N elemental analysis, UV–vis, FT-IR, and single-crystal X-ray diffraction, which revealed that 1 is mononuclear and 2 is dinuclear. Both complexes crystallized in monoclinic space group C2/c. The urease inhibitory activity and in vitro cytotoxic activity of 1 and 2 were tested. The complexes showed strong inhibitory activity against jack bean urease and significantly suppressed the growth of A549, L929, and SW620 cell lines.     

First Total Synthesis of (±)-13-Hydroxyneocembrene

First total synthesis of (±)-13-hydroxyneocembrene ( 1 ), starting from 6-methyl-5-hepten-2-one ( 6 ) and geraniol ( 7 ), is described. The key steps are (i) the addition of sulfur-stabilized carbanion 12 to aldehyde 9 , (ii) the synthesis of 18 by using phase-transfer catalyzed coupling reaction, and (iii) low-valent titanium-induced intramolecular coupling of oxo aldehyde 3 to afford the target molecule after the final deprotection.     

Synthesis of the 11-membered ring of the marine alkaloids, madangamines

The first successful attempt at synthesizing the 11-membered ring of madangamine alkaloids is described. The synthesis involves intramolecular N,O-acetalization of a cyclohexanone derivative, cross-coupling reaction with (Z)-vinylstannane, and intramolecular reductive amination for elaboration of the 11-membered macrocycle.     

Synthesis and cytotoxic activity of new indolylpyrrole derivatives

The current approach described the synthesis of a new series of indolylpyrrole derivatives through multicomponent reaction of α-cyano chalcones, appropriate aldehydes, and ammonium acetate in refluxed acetic acid. The chemical structures of the designed compounds were confirmed with spectroscopic data and elemental analysis and then tested for their in vitro cytotoxic activity by SRB assay method towards three cell lines involving human Prostate adenocarcinoma; metastatic cells (PC-3), human ovary adenocarcinoma (SKOV3) and human dukes' type B, colorectal adenocarcinoma (LS 174 T). Most significant activity provided with compounds 5c, 5h and, 5j against prostate cancer cells (PC-3) with IC50s of 3.30 ± 0.20, 3.60 ± 0.10, and 3.60 ± 0.90 µg/ml, respectively. In human ovarian carcinoma (SKOV3), the compounds 5a, and 5i have stronger cytotoxicity with IC50s of 1.20 ± 0.04, 1.90 ± 0.50 µg/ml, respectively than the standard doxorubicin (IC50 = 2.20 ± 0.02 µg/ml). On the other hand, only compound 5a has the ability to diminish the viability of LS174T cells in an active manner with IC50 2.80 ± 0.10 µg/ml. Consequently, this effort offers groundwork for additional examination of nominated indolylpyrroles as antiproliferative agents.     

Preparation, properties, and reactions of metal-containing heterocycles: Part CV. Synthesis and structure of polyoxadiphosphaplatinaferrocenophanes

A series of novel heterobimetallic crown ether-like polyoxadiphosphaplatinaferrocenophanes cis-[1,1′-Fc(CH₂O(CH₂CH₂O)_nCH₂CH₂PPh₂)₂]PtCl₂ (n=1–3) (4a–c) was synthesized in good yield by cyclization of the bis(phosphine) ligands 1,1′-Fc(CH₂O(CH₂CH₂O)_nCH₂CH₂PPh₂)₂ (n=1–3) (3a–c) and (PhCN)₂PtCl₂ under high dilution conditions in CH₂Cl₂. The bisphosphines 3a–c are obtained by reaction of the corresponding diols 1,1′-Fc(CH₂O(CH₂CH₂O)_nCH₂CH₂OH)₂ (n=1–3) (1a–c) with: (i) CH₃SO₂Cl in CH₂Cl₂ and (ii) LiPPh₂ in THF. Although the X-ray crystal structure of 4a shows that the cavity is large enough for the encapsulation of small metal cations, inclusion experiments of 4a–c with Group 1 cations, and Mg²⁺, or NH₄⁺ in solution applying NMR titration and cyclovoltammetric methods reveal no evidence for the formation of host–guest complexes for 4a,b. In the case of 4c only the addition of Na⁺ or K⁺ leads to an insignificant effect.     

Synthesis and cytotoxic activities of a series of novel N-methylbisindolylmaleimide amino acid ester conjugates

A series of novel N-methylbisindolylmaleimides and natural amino acid conjugates were synthesized and evaluated for their inhibitory activity against six tumor cell lines.Most of the compounds exhibited moderate in vitro cytotoxic activities in the range of 10-100μmol/L.     

Solution-phase synthesis of a muramyl dipeptide analogue MDA

The solution-phase synthesis of a muramyl dipeptide(MDP) analogue of N~α-[4-chlorocinnamoyl-L-alanyl-D-isoglutaminyl]-L-lysine (MDA,2) is reported that possesses the features of easy feasibility,safety and low cost in large scale of synthesis.     

Parallel solution-phase synthesis of substituted 2-(1,2,4-triazol-3-yl)benzimidazoles

A solution-phase synthesis for the preparation of substituted 2-(1,2,4-triazol-3-yl)benzimidazoles from triazole aldehydes and ortho-phenylenediamines has been developed for the purpose of producing diverse lead generation libraries. Crude products were obtained and further purified by mass-guided preparative HPLC.     

Convergent synthesis of oligomers of triazole-linked DNA analogue (DNA) in solution phase

A convergent route for the solution-phase synthesis of oligomeric triazole-linked analogues of DNA (^TLDNA) has been developed. A one-pot procedure for desilylation of masked acetylene and the ensuing copper-catalyzed Huisgen coupling reaction between oligomers allowed the solution-phase synthesis of 7-mer and 8-mer ^TLDNA in good yield.     

Synthesis and preliminary cytotoxic evaluation of substituted indoles as potential anticancer agents

A variety of indole derivatives were designed,synthesized and preliminarily evaluated for their in vitro cytotoxic activity in the A431 and H460 cell lines.All the compounds examined conferred unusual potency in a tumor cell cytotoxicity assay.The findings showed the indole derivatives would be a promising candidate for the development of new anticancer agents.     

Solution-phase synthesis of ICG-001, a β-turn peptidomimetic molecule inhibitor of β-catenin–Tcf-mediated transcription

The solution-phase synthesis of the β-turn peptidomimetic ICG-001, a selective inhibitor of Wnt/β-catenin signalling, which has been found to be important for both initiation and progression of cancers of different tissues and has been exploited as an extremely useful chemogenomic tool, was developed. This route is particularly suitable for the multigram scale preparation of ICG-001.