Metabolomic profile and in vitro evaluation of the cytotoxic activity of Asphodelus microcarpus against human malignant melanoma cells A375

Melanoma is a huge worldwide health problem that must be handled more effectively with better therapeutic options. As a result, new treatment drugs are required to treat this condition. The goal of this study was to investigate the cytotoxic activity of the anthraquinone-rich fractions obtained from Asphodelus microcarpus against human melanoma cell A375. On these melanoma cell lines; the cytotoxicity of these fractions had never been studied before. Liquid chromatography linked to mass spectrometry (LC-MS-MS) and Nuclear Magnetic Resonance was used to determine the chemical profiles of these fractions. The cytotoxicity of the fractions studied was determined by measuring cell viability and calculating IC₅₀ values. Both ethyl acetate (EtOAC) and the precipitate fractions (PPT) exhibited selective cytotoxicity on human melanoma A 375 cell line with IC₅₀ values of 83 and 65 µg/mL, respectively. The antiproliferative properties of EtOAc fraction and PPT were supported by a noticeable decrease in cell numbers during the G2/M cell cycle arrest. Our findings suggest that the anthraquinone content of A. microcarpus tubers is responsible for its anti-proliferative and apoptotic properties and that further in vivo investigations should be conducted to establish the viability of using them to treat human melanomas.     

Novel 2H-pyrazolo[4,3-c]hexahydropyridine derivatives: Synthesis, crystal structure, fluorescence properties and cytotoxicity evaluation against human breast cancer cells

A series of novel 2H-pyrazolo[4,3-c]hexahydropyridine derivatives (II) have been designed and synthesized. The target compounds have been identified by elemental analysis and spectral (¹H NMR, IR, and MS) data and the absolute configuration of compound (II ₁ ) was confirmed by single crystal X-ray diffraction. The cytotoxicity of the target compounds have been evaluated in vitro against two human breast cancer cell lines MCF-7 and MDA-MB-231 by MTT assay. Most compounds exhibited good inhibition, and compounds II ₂₁ (IC₅₀ = 4.7 μM for MCF-7 and IC₅₀ = 9.3 μM for MDA-MB-231), II ₃₃ (IC₅₀ = 2.4 μM for MCF-7 and IC₅₀ = 4.2 μM for MDA-MB-231) and II ₄₀ (IC₅₀ = 3.3 μM for MCF-7 and IC₅₀ =8.6 μM for MDA-MB-231) displayed better inhibitory activity than 5-fluorouracil (IC₅₀ = 4.8 μM for MCF-7 and IC₅₀ = 9.6 μM for MDA-MB-231, respectively). Flow cytometric analysis and DNA fragmentation suggest that II ₃₃ is cytotoxic and able to induce the apoptosis of MCF-7 cells. The fluorescence properties of compounds II ₁ , II ₆ , II ₁₁ , II ₁₆ , II ₂₃ , II ₂₈ , and II ₃₅ were also studied and compound II ₂₈ afforded the highest photoluminescence quantum yield (38%).     

Novel dual inhibitors against FP-2 and PfDHFR as potential antimalarial agents: Design,synthesis and biological evaluation

A series of novel 2,4-diaminopyrimidine-modified compounds was designed and synthesized. Compound 14 showed micromolar dual inhibitory effect on both FP-2 and PfDHFR, and potential inhibition to the proliferation of P. falciparum 3D7 strain and chloroquine-resistant P. falciparum Dd2 strain.     

2-Phenylindole derivatives as anticancer agents: synthesis and screening against murine melanoma,human lung and breast cancer cell lines

Indole derivatives have attractive anticancer properties and may be a future hope for better anticancer drug(s) of low toxicity and high potency. In this paper, syntheses of 2-phenylindole derivatives have been described via Fischer indole synthesis through a one-pot solvent-free method. The synthesized compounds were screened for anticancer potential in vitro against murine melanoma (B16F10), human lung cancer (A549), and human breast cancer (MDA-MB-231) cell lines. The results highlighted that 2-phenylindole derivatives are also promising anticancer agents in case of melanoma and lung cancer along with the breast cancer. Molecular docking analyses with possible targets for melanoma (NEDD4-1) and lung cancer (EGFR) were also performed to understand specific interactions of 2-phenylindole derivatives with the amino acid residues of the receptors.     

Novel 2-aminoimidazole-4-one complexes of copper(II) and cobalt(II): Synthesis,structural characterization and cytotoxicity

A series of 2-aminosubstituted (5Z)-3-phenyl-5-(pyridine-2-ylmethylene)-3,5-dihydro-4H-imidazole-4-ones (L) was prepared by the reaction of the corresponding 2-alkylthio-3,5-dihydro-4H-imidazole-4-ones with morpholine or piperidine in the presence of ytterbium(III) triflate. The resulting ligands were subsequently reacted with CuCl₂·2H₂O and CoCl₂·6H₂O to give the corresponding copper(II) and cobalt(II) complexes, respectively. Analysis revealed that the complexes were formed with an LMCl₂ (M = Cu, Co)-type composition in all cases. The structures of the three cobalt complexes prepared in this way were determined by X-ray crystallography. The results revealed that the cobalt ions in these complexes were tetrahedrally coordinated to two chloride anions and two nitrogen atoms from the pyridine and imidazole moieties of the ligand. The electrochemical properties of the ligands and their complexes were evaluated by cyclic voltammetry, and the results revealed that the first stage in the reduction of the Co(II) and Cu(II) complexes involved the reversible formation of the corresponding Co(I) and Cu(I) complexes, respectively. The cytotoxicity activities of the organic ligands and their complexes were evaluated against several cancer cell lines, including MCF-7, A549 and HEK293 cells. The copper complexes of the organic ligands bearing a phenyl or allyl moiety at their N(3) position together with a piperidine substituent at the 2-position of their imidazolone ring exhibited the greatest cytotoxicity of all of the compounds tested in the current study.     

Novel 1,3,5-thiadiazine-2-thione derivatives containing a hydrazide moiety: Design,synthesis and bioactive evaluation against phytopathogenic fungi in vitro and in vivo

A series of novel 1,3,5-thiadiazine-2-thione derivatives bearing a hydrazide moiety were designed, synthesized and evaluated for their biological activities against phytopathogenic fungi. The antifungal bioassays indicated that the title compound 5b impressively displayed the obvious selectivity and specificity aganist Rhizoctonia solani (Rs) in vitro and in vivo. The above researches provide a significant reference for the further structural optimization of 1,3,5-thiadiazine-2-thione derivatives bearing a hydrazide moiety as potential fungicides.     

Palladium(II) N-heterocyclic carbene complexes: synthesis,structures and cytotoxicity potential studies against breast cancer cell line

Abstract

Mononuclear trans-Pd(II)–NHC complexes (where NHC?=?N-heterocyclic carbene) bearing asymmetrically substituted NHC-ligand have been synthesized via transmetalation reaction between Ag(I)–NHC complexes and [Pd(NCCH₃)₂Cl₂]. The NHC precursors are accessible in two steps by N-n-alkyl reactions of benzimidazole. The resultant benzimidazolium salts were deprotonated with Ag₂O by in situ deprotonation to facilitate the formation of mononuclear Ag(I)–NHC complexes. Single-crystal structural study for Pd(II)–NHC shows that the palladium(II) ion exhibits a square-planar geometry of two NHC ligands and two chloride ions. The cytotoxicity study was investigated against breast cancer cell line (MCF-7). The Ag(I)–NHC complexes exhibit better activities than their corresponding Pd(II)–NHC complexes, whereas all benzimidazolium salts are inactive toward MCF-7 cancer cell line.     

A versatile and practical synthesis of bis(indolyl)methanes/bis(indolyl)glycoconjugates catalyzed by trichloro-1,3,5-triazine

A practical and efficient electrophilic substitution reaction of indoles with a variety of aldehydes was carried out using catalytic trichloro-1,3,5-triazine (10 mol %) in acetonitrile to furnish the corresponding bis(indolyl)methanes in excellent yields. Similarly, sugar derived aldehydes gave hitherto unknown bis(indolyl)glycoconjugates in very good yields.     

Total synthesis of bafilomycin V(1): a methanolysis product of the macrolide bafilomycin C(2)

A synthesis of bafilomycin V(1), a methanolysis product of the macrolide natural product bafilomycin C(2), is described. The route utilizes chiral nonracemic allenylzinc reagents, prepared in situ from propargylic mesylates, to access key segments of this methyl ester. The acetylenic moieties of the derived homopropargylic alcohol adducts play an important role in further elaboration of these subunits. Final assemblage of the 25-carbon chain, containing 12 stereocenters, an alpha-methoxy Z,E 1,3-dienic ester, and an additional E,E 1,3-diene, was achieved through Stille coupling of an acetylene-derived vinyl stannane and vinyl iodide of approximate equal complexity. Attempted cyclization of several C15 hydroxy acid derivatives to the 16-membered lactone bafilomycin A(1), a potent inhibitor of vacuolar ATPases, could not be achieved.     

Sox-4 is a positive regulator of Hep3B and HepG2 cells' apoptosis induced by prostaglandin (PG)A(2) and delta(12)-PGJ(2)

We reported earlier that expression of Sox-4 was found to be elevated during prostaglandin (PG) A(2) and delta(12)-PGJ(2) induced apoptosis in human hepatocarcinoma Hep3B cells. In this study, the role of Sox-4 was examined using human Hep3B and HepG2 cell lines. Sox-4 induction by several apoptotic inducer such as A23187 (Ca(2+) ionophore) and etoposide (topoisomerase II inhibitor) and Sox-4 transfection into the cells were able to induce apoptosis as observed by the cellular DNA fragmentation. Antisense oligonucleotide of Sox-4 inhibited the induction of Sox-4 expression and blocked the formation of DNA fragmentation by PGA(2) and delta(12)-PGJ(2) in Hep3B and HepG2 cells. Sox-4-induced apoptosis was accompanied with caspase-1 activation indicating that caspase cascade was involved in this apoptotic pathway. These results indicate that Sox-4 is involved in Hep3B and HepG2 cells apoptosis as an important apoptotic mediator.     

Stereoselective synthesis of 2-C-branched (acetylmethyl) oligosaccharides and glycoconjugates: Lewis acid-catalyzed glycosylation from 1,2-cyclopropaneacetylated sugars

1,2-Cyclopropaneacetylated sugars as glycosyl donors reacted with a series of glycosyl acceptors (monosaccharides, amino acids, and other alcohols) in the presence of Lewis acid to produce oligosaccharides and glycoconjugates containing 2-C-acetylmethylsugars. Galactosyl donor gave good to excellent α-selectivities with TMSOTf as a catalyst, whereas galactosyl donor offered moderate to good β-selectivities when BF(3)·Et(2)O was used as a catalyst. However, glucosyl donors produced β-exclusive selectivity under both conditions. The stereoselectivities of glycosylation depend on the reactivity of donor sugars and Lewis acid catalyst, which effectively dictated the glycosylation pathways. The evidence suggests that galactosyl donors (e.g., 7) can undergo S(N)1 pathway with a strong Lewis acid (TMSOTf) and S(N)2 pathway under BF(3)·Et(2)O, whereas the glucosyl donors (e.g., 8 and 10) followed S(N)2 pathway. The stereoselectivity was also consequential to the formation of a C2'-acetal intermediate formed via the 2-C-acetylmethyl group and the anomeric carbonium intermediate in glycosylation.     

Novel capto-dative (Z,E)-2-(alkylthio)alk-2-en-4-ynals: synthesis and heterocyclization

An efficient synthesis of new (Z,E)-2-(alkylthio)alk-2-en-4-ynals by aldol condensation reaction of ynals with (alkylthio)-acetaldehydes using NaOH/DMF system has been developed.The reaction of these products with N,N-diphenylethylene-diamine and p-tosylmethyl isocyanide proceeds at the carbonyl group to form the corresponding imidazolidine and oxazole derivatives.     

Ultrasonic green synthesis of silver nanoparticles mediated by Pectin: Characterization and evaluation of the cytotoxicity,antioxidant, and colorectal carcinoma properties

Regarding applicative, facile, green chemical research, a bio-inspired approach is being reported for the synthesis of Ag nanoparticles by pectin as a natural reducing and stabilizing agent without using any toxic and harmful reagent. The biosynthesized Pectin/Ag NPs were characterized by advanced physicochemical techniques like ultraviolet–visible (UV–Vis), Fourier Transformed Infrared spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), High-Resolution Transmission Electron Microscopy (HR-TEM), Energy Dispersive X-ray spectroscopy (EDX), and X-ray Diffraction (XRD) study. It has been established that pectin-stabilized silver nanoparticles have a spherical shape with a mean diameter from 15 to 20 nm. After that, the biological performance of those biomolecules functionalized Ag NPs was investigated. In the MTT assay, human colorectal carcinoma (HCT-8 [HRT-18], Ramos.2G6.4C10, HT-29, and HCT 116) and normal cell lines (HUVEC) were used to study the cytotoxicity and anticancer potential of human colorectal over the AgNO₃ and Pectin/Ag NPs. The cell viability of Pectin/Ag NPs was very low against human colorectal carcinoma cell lines without any cytotoxicity on the normal (HUVEC) cell line. The best anti-human colorectal carcinoma properties of Pectin/Ag NPs against the above cell lines was in the case of the HCT 116 cell line. The antioxidant properties of the AgNO₃ and Pectin/Ag NPs were calculated against DPPH free radicals. The IC50 of Pectin/Ag NPs was 167 µg/mL. According to the above results, the Pectin/Ag NPs may be administrated to treat human colorectal carcinoma in humans.     

Novel (4-oxothiazolidine-2-ylidene)benzamide derivatives: synthesis,characterization and crystal structures

Research on Chemical Intermediates - A convenient, one-pot, multicomponent synthesis of new (4-oxothiazolidine-2-ylidene)benzamide derivatives by unsymmetrical thioureas, various amines and methyl...     

Two Cu(I) complexes based on semicarbazone ligand: synthesis,crystal structure,Hirshfeld surface and anticancer activity evaluation against human cell lines

Structural Chemistry - Two novel Cu(I) complexes with the 2-acetylpyridine-N(4)-phenyl semicarbazone (HL) ligand, [CuCl (HL)(PPh3)]∙CH3CN (1) and [CuBr (HL)(PPh3)] (2), were investigated by...     

Novel,short, stereospecific synthesis of lyxo-(2R,3R,4R)-phytosphingosine and erythro-(2R,3S)-sphingosine

Lyxo-phytosphingosine and erythro-sphingosine have been elaborated from a common intermediate. The key step in the reaction sequence involves stereo- and regiospecific functionalization of an olefin by intramolecular nucleophilic sulfinyl group participation.     

Novel,efficient and stereospecific synthesis of xylo-(2R,3S,4S)-phytosphingosine and threo-(2R,3R)-sphingosine

The stereo- and regioselective elaboration of a bromohydrin from an olefinic precursor and Pummerer ene reaction for carboncarbon bond formation are the key steps in a novel and flexible synthesis of xylo-phytosphingosine and threo-sphingosine.     

Design, synthesis, and biological evaluation of a library of 1-(2-thiazolyl)-5-(trifluoromethyl)pyrazole-4-carboxamides

A library of 422 1-(2-thiazolyl)-5-(trifluoromethyl)pyrazole-4-carboxamides was prepared in five steps using solution-phase chemistry. The first step in the synthesis was the reaction of ethyl 2-ethoxymethylene-3-oxo-4,4,4-trifluorobutanoate with thiosemicarbazide, which is reported in the literature to afford a 1:1 mixture of ethyl 1-thiocarbamoyl-5-(trifluoromethyl)pyrazole-4-carboxylate and ethyl 1-thiocarbamoyl-3-(trifluoromethyl)pyrazole-4-carboxylate. We reassigned the structure of the product to be a single compound, ethyl 5-hydroxy-1-thiocarbamoyl-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazole-4-carboxylate. This common intermediate was diversified by reaction with 17 alpha-bromoketones affording, in two steps, 17 1-(2-thiazolyl)-5-(trifluoromethyl)pyrazole-4-carboxylic acids. Scavenger resins were used to facilitate formation and purification of up to 27 amides from each of these acids in the last step. In addition, the Curtius reaction was applied to 12 of the acids followed by quenching with alcohols to afford a 108-member carbamate library. Certain compounds in the two libraries were toxic to C. elegans.