Synthesis and antiproliferative activities of aminoalkylated polymethoxyflavonoid derivatives

A series of novel aminoalkylated polymethoxyflavonoid derivatives 3–11 was synthesised from 5-hydroxy-3,7,3′,4′-tetramethoxyflavonoid (1) through extending alkoxy chain at the 5-position, and introducing amine hydrogen bond receptor at the end of the side chain. Their antiproliferative activities were evaluated in vitro on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3). The results showed that all the target compounds exhibited antiproliferative activities against investigated cancer cells with IC₅₀ values of 9.51–53.33 μM. Compounds 5, 7, 8, 11 on Hela cells and compounds 4–9, 11 on HCC1954 exhibited more potency as compared to positive control cis-Platin.     

A review of self-organising 2,5- and 2,4-disubstituted 1,3-thiazole-containing materials: synthesis,mechanisms and tactics

ABSTRACT

2,5- and 2,4-disubstituted 1,3-thiazoles have been incorporated as core units in thermotropic liquid crystalline materials. However, synthetic approaches to these systems have been somewhat limited, and this is reflected in the relatively few reports of these mesogenic systems. This paper highlights both recent and well-established synthetic approaches to these systems using ring closure (Gabriel- and Hantzsch-type approaches) methodology and modifications of an intact 1,3-thiazole ring. The scope and limitations of each of these approaches are discussed.     

Synthesis of 5,6-dihydro-4H-1,3-thiazine containing peptide mimics from N-(3-hydroxypropyl)thioamides and epimerization studies

The first synthesis of 1,3-thiazine fused peptide mimics is described from N-(3-hydroxypropyl)thioamides under MsCl/NEt₃ conditions. The method is amenable to oligopeptidomimics with polar and apolar side chains. Substantial epimerization occurs at chiral C(2) exo methines in non-Pro fused mimics even under neutral conditions. ¹H NMR and crystal structure analyses indicate that the Thi analogues primarily associate with each other through intermolecular hydrogen bonds, involving the nitrogen of 1,3-thiazine and the N–H of the fused residue, which may be the basis for enamination–racemization process in these peptide mimics.     

Oxidation of thiazolo[3,2-a]pyrimidin-3(2H)-ones with DMSO and Lawesson’s reagent

2,2′-Dimers with a central double bond were prepared by the oxidation of 5,6-disubstituted 7-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-3(2H)-ones with DMSO and Lawesson’s reagent at room temperature. The role of DMSO as an oxidizing reagent was confirmed by NMR spectroscopy. The E-configuration of the central CC bond for the two diastereomers of compound 8m was proven by single crystal X-ray data. The dimeric thiazolopyrimidines were orange or red colored and absorption bands at 283–330 and 459–476?nm were observed in the UV spectra.     

Syntheses,characterization of and studies on the electrochemical behaviour of ferrocenyl dithiophosphonates and 4-methoxyphenyl dithiophosphonates

Some 1,3-dithiadiphosphetane 2,4-disulfides (X₂P₂S₄, X: Fc, FcLR; X: CH₃O?C₆H₄?, LR) were allowed to react with alcohols to obtain dithiophosphonic acids (X(OR)PS₂H). These were converted to the corresponding ammonium salts. The salts were of the structures [Fc(OR)PS₂]^?[NH₄]⁺, R: 3-methyl-1-butyl- for I; 1-phenyl-1-propyl- for II; 3-pentyl- for III; 3-phenyl-1-propyl- for IV and [CH₃O?C₆H₄(OR)PS₂]^?[NH₄]⁺, R: 3-methyl-1-butyl- for V and 1-phenyl-1-propyl- for VI. To the best of our knowledge, all the compounds except V were prepared for the first time.

The compounds synthesized were characterized by elemental analysis, NMR (¹H, ¹³C, ³¹P), MS, FTIR, and Raman spectroscopies. Electrochemical behaviors of I–VI at disposable pencil graphite electrode (PGE) were investigated by using cyclic voltammetry (CV) and square-wave voltammetry (SWV). Adsorption and diffusion patterns of all the compounds on the PGE were also studied.

Two electroactive groups were identified in the compounds I–IV and only one in V and VI. The ferrocenyl groups of I-IV were oxidized at around 0.4 V. The same compounds display a second, more intense CV band at 0.8 V. The corresponding band for the compounds V–VI appears at around 0.6 V with a much weaker intensity. It is suggested that the ferrocenyl group introduced into the structures stabilizes the radical species formed as the product of the oxidation of the dithiophosphonato group.     

Synthesis and antiproliferative activities of 5-azacytidine analogues in human leukemia cells

Twenty-six 5-azacytidine analogues have been synthesized, including 4-amino- 6-alkyl-1-pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H)-ones 1a-j, 6-amino-4-alkyl/aryl-1- pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H)-ones 2a-f and 4-amino-6-alkyl-1,3,5-triazin-2- yl-1-thio-pyranosides/ribofuranosides 3a-j. The antiproliferative activities of these synthetic analogues were investigated in human leukemia HL-60 cells. Ribofuranosyl S-nucleoside 3a, a bioisostere of 5-azacytidine, had a similar antiproliferative ability as that of the latter. Introduction of a methyl at the 6 position of 5-azacytidine and/or replacement of the ribofuranosyl moiety with pyranosyl sugars or disaccharides significantly decreased the antiproliferative activities of the 5-azacytidine derivatives. Several compounds with the replacement of pyranosyl sugars enhanced all-trans retinoic acid-induced differentiation ability in human leukemia HL-60 cells.     

Echinophora tenuifolia L. branches phytochemical profile and antiproliferative activity on human cancer cell lines

Abstract

The methanolic extract of Echinophora tenuifolia L. branches and its fractions were evaluated for their in vitro cell growth inhibitory activity on different human cancer cell lines (C32, LoVo and SKBr3) and the normal BJ fibroblasts. All tested samples were effective against the melanoma cell line C32, with IC₅₀ values ranging from 22.8?±?0.8 to 78.7?±?1.2?μg/mL, the antiproliferative activity of the dichloromethane fraction being significantly higher. This fraction was also effective against the LoVo adenocarcinoma cell line, with an IC₅₀ value of 53.0?±?2.1?μg/mL. The ethyl acetate and dichloromethane fractions showed the highest lipid peroxidation inhibitory activity, verified by means of the β-carotene bleaching test. The phytochemical profiles of E. tenuifolia branches extract were established by means of GC-MS and HPTLC. Overall, branches of E. tenuifolia L. could represent a rich source of bioactive compounds, potentially useful in the pharmaceutical field.     

Composition,antibacterial, antioxidant and antiproliferative activities of essential oils from three Origanum species growing wild in Lebanon and Greece

The essential oils from Origanum dictamnus, Origanum libanoticum and Origanum microphyllum were analysed by GC-MS, finding carvacrol, p-cymene, linalool, γ-terpinene and terpinen-4-ol as major components. The antioxidant activity by the DPPH and FRAP tests and the antiproliferative activity against two human cancer cell lines, LoVo and HepG2, were investigated, showing that the essential oil of O. dictamnus was statistically the most inhibitory on both the cell lines, while all the oils exerted a weak antioxidant activity. Furthermore, the samples were tested against 10 Gram-negative and Gram-positive bacteria; all the oils were active on Gram-positive bacteria but O. dictamnus essential oil was the most effective (MIC = 25–50 μg/mL), showing also a good activity against the Gram-negative Escherichia coli (MIC = 50 μg/mL). Data suggest that these essential oils and particularly O. dictamnus oil could be used as valuable new flavours with functional properties for food or nutraceutical products.     

Synthesis,antimicrobial and antiproliferative activities of new self-assembly benzimidazole-bridged aren ruthenium rectangles in human breast cancer cells

Journal of Inclusion Phenomena and Macrocyclic Chemistry - Some novel benzimidazole-bridged aren ruthenium rectangle compounds of the general structure...     

Synthesis,structure and antiproliferative and optical activities of two new biphenyl‐derived Schiff bases

Two novel Schiff bases derived from indole and biphenyl have been designed and synthesized, namely 3‐((E)‐{(E)‐[1‐(biphenyl‐4‐yl)ethylidene]hydrazinylidene}methyl)‐1‐methyl‐1H‐indole ( 3‐BEHMI ) acetonitrile monosolvate, C₂₄H₂₁N₃·CH₃CN, and 3‐((E)‐{(E)‐[1‐(biphenyl‐4‐yl)ethylidene]hydrazinylidene}methyl)‐1‐methyl‐1H‐indole ( 3‐BEHEI ) acetonitrile monosolvate, C₂₄H₂₁N₃·CH₃CN. Their structures were characterized by elemental analysis, quadrupole time‐of‐flight MS, NMR and UV–Vis spectroscopy. The single‐crystal packing structure of 3‐BEHMI is largely dominated by C—H…π interactions and weak van der Waals interactions. The in vitro cytotoxicity of the two title compounds have been evaluated against two tumour cell lines (A549 human lung cancer and 4T₁ mouse breast cancer) and two normal cell lines (MRC‐5 normal lung cells and NIH 3T3 fibroblasts) by MTT assay. The results indicate that 3‐BEHEI exhibits a slightly weaker antiproliferative capability (IC₅₀ = ～50 µM) than the previously reported similar Schiff base 3‐BEHI (IC₅₀ = ～20 µM). This is in line with docking results. 3‐BEHMI demonstrates a weak cytotoxic activity, with IC₅₀ values around 110 µM, which disagrees with its docking results. Overall, the tested compounds manifest relevant cytotoxicities on the selected cancer cell lines and normal cell lines. The UV–Vis and fluorescence spectra were recorded and reproduced through the TD‐DFT method with four types of hybrid density functionals, including B3LYP, M062X, PBE1PBE and WB97XD.     

Anti-inflammatory and antiproliferative activities of Ixora brevifolia Benth. (Rubiaceae)

The crude extract and fractions from the branches of Ixora brevifolia, a tree found in the Brazilian Cerrado, were tested for anti-inflammatory and in vitro antiproliferative effects. The crude extract and n-hexane fraction exhibited significant inhibition of ear oedema in mice, while n-hexane-precipitated and chloroform fractions strongly inhibited the myeloperoxidase activity in ear tissue. The n-hexane and n-hexane-precipitated fractions showed strong growth inhibition for glioma cell line and the hydromethanolic fraction inhibited the growth of leukaemia cell line.     

Facile Synthesis of Five-membered Phosphoroheterocycles Bearing N-P-N and S-P-N Moieties

In past decades, Lawesson reagent (LR) has aroused extensive interests of chemists. Various papers on LRs structure, physical and chemical properties appeared in literature1~5, application of its unique reactivity in the synthesis of bio-active compounds also attracted much attention6,7. In particular, some potential bio-active phosphorus heterocycles could be novelly prepared by reacting LR with proper functional compound8. Peterson reported that the reaction of LR with 3-oxo-propaneni…     

Thionation of Chalcone and Aurone Derivatives by Lawesson's Reagent

Abstract

The reaction of Lawesson's reagent (LR 5) with chalcones (4a–h) and aurones (12a–h) proceeds in refluxing toluene to give the respective benzofuranylprop-2-en-1-thiones (8a–h) and benzodifuran-3-thiones (13a–h). Correct elemental analyses and spectroscopic data were obtained for the new compounds.     

Synthesis and antimicrobial evaluation of some novel pyrido[3,2-f][1,2,3]thiadiazaphosphepinone compounds,bearing a pyridine moiety

Several pyridothiadiazaphosphepinones (3–9) were synthasized by combining tetraphosphorus decasulfide, Lawesson's reagent, phosphorus tribromide, and P,P-dichlorophenyl phosphine with 2-(aminosulfanyl)-6-(3,4-dichlorophenyl)-4-(furan-2-yl)-5-oxo-5,6-dihydropyridine-3-carbonitrile (2). The reaction mechanisms for these products were discussed. On the basis of elemental analysis and spectrum data, the structures of the newly synthesized compounds were determined. The biological activity of every synthesized compound was examined against various microorganisms using the disc diffusion method. The bulk of the microorganisms tested are effectively inhibited by the newly synthesized chemicals.     

Scope and Limitation of the Reactions of 3-Imino Derivatives of Pentane-2,4-Diones with Organophosphorus Reagents

Abstract

3-(Hydroxyimino)pentane-2,4-dione reacts with phosphonium ylides, Wittig–Horner reagents, trialkyl phosphites, and Lawesson's reagents to give the olefinic and cyclic products, the phosphonate adducts, the dialkyl phosphate products, the phosphinodithioic acid, and 2,4-dithione products, respectively. Furthermore, the reaction of 3-(phenylimino)pentane-2,4-dione with Wittig, Wittig–Horner reagents and trialkyl phosphite resulted in the formation of 2,5-diendioate, diethoxy phosphoryl hexanoate and the phosphate products. Possible reaction mechanisms are considered and the structural assignments are based on analytical and spectroscopic results. The antibacterial and antifungal activities for some of the new compounds are also reported.     

Synthesis,Spectroscopic Analysis,and In-Vitro Antimicrobial Evaluation of some Tetrahydrobenzo[a]Xanthene-11-Thiones

Abstract

A series of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-thiones were synthesized by the reaction of substituted 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-ones with Lawesson's Reagent in toluene under standard reaction conditions. All synthesized compounds were characterized by IR, NMR (¹H and ¹³C), and mass spectra. Moreover, 2D-NMR (HOMOCOSY, HSQC, and HMBC) studies were also performed for compound 10b. The synthesized compounds were also screened for their antibacterial activities.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental files: Additional figures.]     

Synthesis,crystal structures,antiproliferative activities and reverse docking studies of eight novel Schiff bases derived from benzil

Eight novel Schiff bases derived from benzil dihydrazone ( BDH ) or benzil monohydrazone ( BMH ) and four fused‐ring carbonyl compounds (3‐formylindole, FI ; 3‐acetylindole, AI ; 3‐formyl‐1‐methylindole, MFI ; 1‐formylnaphthalene, FN ) were synthesized and characterized by elemental analysis, ESI–QTOF–MS, ¹H and ¹³C NMR spectroscopy, as well as single‐crystal X‐ray diffraction. They are (1Z,2Z)‐1,2‐bis{(E)‐[(1H‐indol‐3‐yl)methylidene]hydrazinylidene}‐1,2‐diphenylethane ( BDHFI ), C₃₂H₂₄N₆, (1Z,2Z)‐1,2‐bis{(E)‐[1‐(1H‐indol‐3‐yl)ethylidene]hydrazinylidene}‐1,2‐diphenylethane ( BDHAI ), C₃₄H₂₈N₆, (1Z,2Z)‐1,2‐bis{(E)‐[(1‐methyl‐1H‐indol‐3‐yl)methylidene]hydrazinylidene}‐1,2‐diphenylethane ( BMHMFI ) acetonitrile hemisolvate, C₃₄H₂₈N₆·0.5CH₃CN, (1Z,2Z)‐1,2‐bis{(E)‐[(naphthalen‐1‐yl)methylidene]hydrazinylidene}‐1,2‐diphenylethane ( BDHFN ), C₃₆H₂₆N₄, (Z)‐2‐{(E)‐[(1H‐indol‐3‐yl)methylidene]hydrazinylidene}‐1,2‐diphenylethanone ( BMHFI ), C₂₃H₁₇N₃O, (Z)‐2‐{(E)‐[1‐(1H‐indol‐3‐yl)ethylidene]hydrazinylidene}‐1,2‐diphenylethanone ( BMHAI ), C₂₄H₁₉N₃O, (Z)‐2‐{(E)‐[(1‐methyl‐1H‐indol‐3‐yl)methylidene]hydrazinylidene}‐1,2‐diphenylethanone ( BMHMFI ), C₂₄H₁₉N₃O, and (Z)‐2‐{(E)‐[(naphthalen‐1‐yl)methylidene]hydrazinylidene}‐1,2‐diphenylethanone ( BMHFN ) C₂₅H₁₈N₂O. Moreover, the in vitro cytotoxicity of the eight title compounds was evaluated against two tumour cell lines (A549 human lung cancer and 4T₁ mouse breast cancer) and two normal cell lines (MRC‐5 normal lung cells and NIH 3T3 fibroblasts) by MTT assay. The results indicate that four ( BDHMFI , BDHFN , BMHMFI and BMHFN ) are inactive and the other four ( BDHFI , BDHAI , BMHFI and BMHAI ) show severe toxicities against human A549 and mouse 4T₁ cells, similar to the standard cisplatin. All the compounds exhibited weaker cytotoxicity against normal cells than cancer cells. The Swiss Target Prediction web server was applied for the prediction of protein targets. After analyzing the differences in frequency hits between these active and inactive Schiff bases, 18 probable targets were selected for reverse docking with the Surflex‐dock function in SYBYL‐X 2.0 software. Three target proteins, i.e. human ether‐á‐go‐go‐related (hERG) potassium channel, the inhibitor of apoptosis protein 3 and serine/threonine‐protein kinase PIM1, were chosen as the targets. Finally, the ligand‐based structure–activity relationships were analyzed based on the putative protein target (hERG) docking results, which will be used to design and synthesize novel hERG ion channel inhibitors.     

Synthesis,structure and antiproliferative activity of dinuclear ruthenium arene complexes with differently coordinated thiosemicarbazones

A series of di‐nuclear ruthenium arene complexes with TSC ligands ([(η⁶‐p‐cymene)Ru(N¹,S‐TSC)]₂Cl₂, A‐type, 1 and 2 ) and their corresponding analogues ([(η⁶‐p‐cymene)Ru(N²,S‐TSC)]₂Cl₂, B‐type, 3 and 4 ), in which TSCs act as different coordination mode, have been synthesized and structurally characterized by a variety of physical methods. The molecular structures of 1 , 3 and 4 were determined using single‐crystal X‐ray diffraction analysis. The Gibbs free energy of the two examples of the two types of complexes ( 1 and 3 ) and bonding order in their single‐crystals were discussed using density functional theory (DFT) calculations. The compounds were further evaluated for their in vitro antiproliferative activities against several cancerous and HEK‐293 T noncancerous cell lines, and the results indicate that B‐type complexes show stronger cytotoxicity than A‐type complexes. Furthermore, the interactions of the compounds with DNA were investigated by electrophoretic mobility spectrometry studies.     

Synthesis,molecular docking,antimicrobial, antiquorum-sensing and antiproliferative activities of new series of pyrazolo[3,4-b]pyridine analogs

New series of pyrazolo[3,4-b]pyridines were prepared and evaluated for antimicrobial activity toward six selected microorganisms. Compounds 2a, 3b, 3d and 3e exhibited good activity toward B. cereus. On the other hand, 2a and 3b evinced interesting activity over C. albicans, whereas 2a, 3b and 3e displayed promising activity over A. fumigatus. Antiquorum-sensing effectiveness of the new members over C. violaceum was also assessed, where compounds 2a and 3b exhibited higher activity than that of the reference compound, indole. In vitro antiproliferative assessment toward HepG2, HCT-116 and MCF-7 cancer cells evidenced that 2f has notable effectiveness on all examined cell lines, whereas 3a–c were active but to a lower extent. In vivo antitumor activity of 2f and 3a–c against EAC cells was also esteemed, where 2f and 3c showed considerable activity comparable to that of doxorubicin. Cytotoxicity screening over WI38 and WISH normal cells evinced that 2f and 3a–c are less cytotoxic than doxorubicin. Compounds 2a, 2f, 3a–c and 3e were evaluated for DNA-binding affinity and topoisomerase IIβ inhibitory activity. Analogs 2a, 2f, 3a and 3b illustrated strong DNA-binding affinity, whereas 2a, 2f and 3a exhibited interesting topoisomerase IIβ inhibitory activity. Compounds 2a and 2f were docked into topoisomerase IIβ, where 2f showed preferential binding to topoisomerase IIβ. Computational studies articulated that the new members are in compliance with Veber's standards and Lipinski’s rule.     

Synthesis,structure and antiproliferative activity of organometallic iridium(III) complexes containing thiosemicarbazone ligands

A series of half‐sandwich iridium complexes ( 1 – 4 ) with thiosemicarbazone ligands in two types of coordination modes were synthesized and characterized. The molecular structures of compounds 1 , 2 and 3 were determined using single‐crystal X‐ray diffraction analysis. The nature of the complexes was studied using density functional theory calculations. The stability of the complexes was investigated using UV–visible absorption spectroscopy. The compounds were further evaluated for their in vitro antiproliferative activities against HeLa, HepG2, CNE‐2, SGC‐7901, KB and HEK‐293 T cell lines. Compound 2 displays the highest antiproliferative activity among the other analogues and cisplatin.