New synthesis of indole-7-carboxylic acid

A new preparative method for the synthesis of indole-7-carboxylic acid has been developed, consisting in reductive cyclization of -(dimethylamino)-3-carbo-methoxy-2-nitrostyrene by the action of iron in acetic acid.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 44–45, January, 1986.     

Plant-assisted synthesis of gold nanoparticles for photocatalytic,anticancer, and antioxidant applications

The current study is the first to disclose a quick, cost-effective, and environmentally safe phytofabrication of gold nanoparticles (AuNPs) that remained stable for three months utilizing the aqueous extract of T. capensis leaves to uphold the principles of green chemistry such as less hazardous chemical syntheses, safer solvents and auxiliaries, design for energy efficiency, and use of renewable feedstocks. Several approaches were used to describe T. capensis-AuNPs, with the findings revealing the successful phytoformation of crystalline AuNPs with a dark brown color, spherical nanoparticles with a size range of 10–35 nm, a surface plasmon peak at 515 nm, and a surface charge of ? 24.5 mV. T. capensis-AuNPs showed 72% photodegradation efficacy against malachite green. The MTT experiment revealed that T. capensis-AuNPs and T. capensis extract had excellent potency in preventing the development and proliferation of human breast cancer cells (MCF7 cell line), with IC50 values of 9.6 g/mL and 23.3 g/mL, respectively. Both T. capensis-AuNPs and T. capensis extract had significant antioxidant efficacies, with DPPH scavenging percentages of 70.73% for T. capensis-AuNPs and 85.62% for T. capensis extract. Consequently, these findings suggest a new and sustainable route for the green synthesis of AuNPs using the aqueous extract of T. capensis.     

Plant phenolics: extraction, analysis and their antioxidant and anticancer properties

Phenolics are broadly distributed in the plant kingdom and are the most abundant secondary metabolites of plants. Plant polyphenols have drawn increasing attention due to their potent antioxidant properties and their marked effects in the prevention of various oxidative stress associated diseases such as cancer. In the last few years, the identification and development of phenolic compounds or extracts from different plants has become a major area of health- and medical-related research. This review provides an updated and comprehensive overview on phenolic extraction, purification, analysis and quantification as well as their antioxidant properties. Furthermore, the anticancer effects of phenolics in-vitro and in-vivo animal models are viewed, including recent human intervention studies. Finally, possible mechanisms of action involving antioxidant and pro-oxidant activity as well as interference with cellular functions are discussed.     

7-Pyridylindoles: synthesis, structure, and properties

A series of three isomeric 7-pyridylindoles (7-PIs) are prepared where the pyridine attachment is through C2, C3, or C4. These systems are prepared by a combination of the Bartoli reaction and the Stille coupling with an appropriate pyridyl stannane. By treatment with CH(3)I, the 7-PIs can be converted to their pyridinium salts. Deprotonation at the NH of these salts leads to a zwitterion which, in the 4-pyridyl system, also exists as a neutral isomer. The photophysical and NMR properties of these systems are discussed. All three pyridylindoles are analyzed by X-ray crystallography and shown to exist in different states of aggregation dictated by the formation of intra- and intermolecular H-bonds.     

Fullerene-derivatized amino acids: synthesis, characterization, antioxidant properties, and solid-phase peptide synthesis

A series of [60]fullerene-substituted phenylalanine (Baa) and lysine derivatives have been prepared by the condensation of 1,2-(4'-oxocyclohexano)fullerene with the appropriately protected (4-amino)phenylalanine and lysine, respectively. Conversion of the imine to the corresponding amine is achieved by di-acid catalyzed hydroboration. The reduction of the imine is not accompanied by hydroboration of the fullerene cage. The [70]fullerene phenylalanine derivative has also been prepared as have the di-amino acid derivatives. The compounds were characterized by MALDI-TOF mass spectrometry, UV/Vis spectroscopy, and cyclic voltammetry. 1H and 13C NMR spectroscopy allowed the observation of diastereomers. Fullerene-substituted peptides may be synthesized on relatively large scale by solid-phase peptide synthesis. The presence of the C60-substituted amino acid in a peptide has a significant effect on the secondary structures and self-assembly properties of peptides as compared to the native peptide. The antioxidant assay of Baa and a Baa-derived anionic peptide was determined to be significantly more potent than Trolox.     

Synthesis and biological evaluation of indole-2-carbohydrazides and thiazolidinyl-indole-2-carboxamides as potent tubulin polymerization inhibitors

A new series of N’-(substituted phenyl)-5-chloro/iodo-3-phenyl-1H-indole-2-carbohydrazide (5, 6) and N-[2-(substituted phenyl)-4-oxo-1,3-thiazolidin-3-yl]-5-iodo/chloro-3-phenyl-1H-indole-2-carboxamide (7, 8) derivatives were synthesized and evaluated for their anticancer properties. Compounds 5a and 6b, selected as prototypes by the National Cancer Institute for screening against the full panel of 60 human tumor cell lines at a minimum of five concentrations at 10-fold dilutions, demonstrated remarkable antiproliferative activity against leukemia, non-small cell lung cancer, colon cancer, central nervous system (CNS) cancer, melanoma, ovarian cancer, renal cancer, and breast cancer (MCF-7) cell lines with GI₅₀ values < 0.4 μM. A subset of the compounds was then tested for their potential to inhibit tubulin polymerization. Compounds 6f and 6g showed significant cytotoxicity at the nM level on MCF-7 cells and exhibited significant inhibitory activity on tubulin assembly and colchicine binding at about the same level as combretastatin A-4. Finally, docking calculations were performed to identify the binding mode of these compounds. Group 5 and 6 compounds interacted with the colchicine binding site through hydrophobic interactions similar to those of colchicine. These compounds with antiproliferative activity at high nanomolar concentration can serve as scaffolds for the design of novel microtubule targeting agents.     

Synthesis and properties of substituted 2-thioxohexahydropyrimidine-5-carbohydrazides

A regioselective method for the synthesis of substituted (4R*,5S*,6R*)-2-thioxohexahydro-pyrimidine-5-carbohydrazides from the corresponding diastereomers of hexahydro-2H-chromeno[4,3-d]pyrimidines was developed. In acidic medium, the obtained hydrazides are prone to retro reaction to give hexahydro-2H-chromeno[4,3-d]pyrimidines.

     

Synthesis of imidazo[1,2-a]pyridine-6-carbohydrazides and 1H-pyrido[1,2-a]pyrimidine-7-carbohydrazides

The one-pot, multicomponent synthesis of imidazopyridine and pyridopyrimidine fused heterocyclic systems from readily available diamines, l,l-bis(methylthio)-2-nitroethene, cyanoacetohydrazide and aromatic aldehydes in good to high yields is described. This protocol has the advantages of simple work-up, mild reaction conditions, absence of catalyst and provides an entry point to fused heterocyclic structures.     

Ferrocenoyl pyridine arene ruthenium complexes with anticancer properties: synthesis, structure, electrochemistry, and cytotoxicity

Organometallic ruthenium(II) complexes of general formula [Ru(eta(6)-arene)Cl(2)(NC(5)H(4)OOC-C(5)H(4)FeC(5)H(5))], where arene = C(6)H(6) (1), C(6)H(5)Me (2), p-iPrC(6)H(4)Me (3), and C(6)Me(6) (4), and of general formula [Ru(eta(6)-arene)Cl(2)](2)(NC(5)H(4)OOC-C(5)H(4)FeC(5)H(4)-COOC(5)H(4)N), where arene = p-iPrC(6)H(4)Me (5) and C(6)Me(6) (6), have been synthesized and characterized, the molecular structures of these complexes being confirmed by single-crystal X-ray structure analysis of complex 4 as a representative example. The redox properties and in vitro anticancer activities of complexes 1-6 have been studied. All the compounds are moderately cytotoxic toward the A2780 and A2780cisR (cisplatin-resistant) human ovarian carcinoma cell lines. The diruthenium arene complexes 5 and 6 are about twice as active as their mononuclear analogues 3 and 4. Cyclic voltammetry revealed a good correlation of the RuII/RuIII redox potentials of 1-4 and the number of alkyl substituents in the arene ligand.     

One-pot three-component synthesis of indole-3-glyoxyl derivatives and indole-3-glyoxyl triazoles

A general and efficient reaction of indole with oxalyl chloride and nucleophiles providing indole-3-glyoxyl derivatives has been developed in mild conditions. In the same fashion, the other reaction involved the addition of organic azides leading to the synthesis of indole-3-glyoxyl-1,2,3-triazoles, which proceeds smoothly generating the products in moderate to high yields.     

New fused pyrazolopyrimidine derivatives; heterocyclic styling,synthesis, molecular docking and anticancer evaluation

Novel pyrazolopyrimidines and their fused derivatives derived from aminopyrazole moiety as pyrazoloquinazoline, chromenopyrazolopyrimidine, pyrazolopyrimidopyrimidine, pyrazolopyrimidotriazepine and benzoimidazopyrazolopyrimidine were designed, synthesized and evaluated for their anticancer activities. Twenty of the synthesized compounds were tested by the National Cancer Institute (NCI, Bethesda, USA) at a single high dose (10^-5 M). It was found that 5-amino-1H-pyrazole-4-carbonitrile derivative, pyrazolo[5,1-b]quinazoline-11-carbonitrile derivative and 1-amino-2,4-dihydro-5H-benzo[4,5]imidazo[1,2-c]pyrazolo[4,3-e]pyrimidin-5-one were own widely selective powerful anticancer activity towards certain cancer cell lines and this also proved through docking studies with cyclooxygenase-2 (COX-2) enzyme.     

4,9-Dihydrobenz[f]indole-4,9-dione derivatives synthesis and properties of 2,3,4,9-tetrahydrobenz[f]indole-2,4,9-triones and 2,3,4,9-tetrahydrobenz[f]indole-2,3,4,9-tetrones

Under the influence of amines, (3-chloro-1,4-naphthoquinon-2-yl)malonic ester is cyclized to 3-carbethoxy derivatives of 2,3,4,9-tetrahydrobenz[f]indole-2,4,9-trione, which were decarboxylated and then oxidized to 2,3,4,9-tetrahydrobenz[f]indole-2,3,4,9-tetrone derivatives. Methylation of 2,3,4,9-tetrahydrobenz[f]indole-2,4,9-triones leads to a mixture of O- and C-methyl derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 911–914, July, 1976.     

Microwave assisted synthesis of disubstituted benzyltin arylformylhydrazone complexes: anticancer activity and DNA‐binding properties

Eight disubstituted benzyltin complexes, i.e., {[R(O)C=N‐N=C (Me)COO]R'₂Sn(CH₃OH)}_n ( 1a and 2b ), {[R(O)C=N‐N=C (Me)COO]R'₂Sn(CH₃OH)}₂ ( 1b and 1d ) and {[R(O)C=N‐N=C (Me)COO]R'₂Sn}_n ( 1c , 2a , 2c , and 2d ) (R = C₄H₃O‐, C₄H₃S‐, p–t‐Bu‐C₆H₄‐ or p‐MeO‐C₆H₄‐; R' = o‐Cl‐C₆H₄CH₂‐ or o‐Me‐C₆H₄CH₂‐), were prepared from the reaction of arylformylhydrazine, pyruvic acid and disubstituted benzyltin dichloride with microwave irradiation. All complexes were characterized by FT‐IR spectroscopy, ¹H, ¹³C and ¹¹⁹Sn NMR spectroscopy, HRMS, elemental analysis, X‐ray single‐crystal diffraction and TGA. The in vitro antitumour activities of all complexes were evaluated by an MTT assay against three human cancer cell lines (NCI‐H460, HepG2, and MCF7). 2b exhibited strong antitumour activity on HepG2 cells and was expected to be a suitable platform for further chemical optimization to develop as anticancer therapeutics. The DNA binding of 2b was studied by UV–visible absorption spectrometry, fluorescence competitive assays, viscosity measurements and gel electrophoresis. Molecular docking was used to predict the binding between 2b and DNA, and the results show that 2b can become embedded in the double helix of DNA and cleave DNA.     

Microwave-assisted synthesis and antioxidant properties of hydrazinyl thiazolyl coumarin derivatives

ABSTRACT: Coumarin derivatives exhibit a wide range of biological properties including promising antioxidant activity. Furthermore, microwave-assisted organic synthesis has delivered rapid routes to N- and O-containing heterocycles, including coumarins and thiazoles. Combining these features, the use of microwave-assisted processes will provide rapid access to a targeted coumarin library bearing a hydrazino pharmacophore for evaluation of antioxidant properties. RESULTS: Microwave irradiation promoted 3 of the 4 steps in a rapid, convergent synthesis of a small library of hydrazinyl thiazolyl coumarin derivatives, all of which exhibited significant antioxidant activity comparable to that of the natural antioxidant quercetin, as established by DPPH and ABTS radical assays. CONCLUSIONS: Microwave dielectric heating provides a rapid and expedient route to a series of hydrazinyl thiazolyl coumarins to investigate their radical scavenging properties. Given their favourable properties, in comparison with known antioxidants, these coumarin derivatives are promising leads for further development and optimization.     

Determination of the chemical composition and antioxidant,anticancer, and antibacterial properties of essential oil of Pulicaria crispa from Saudi Arabia

Essential oils obtained from plants play critical roles in food and medicine. In this study, the phytochemical composition of Pulicaria crispa essential oil, and its antibacterial, antioxidant and anticancer properties were determined in vitro. The essential oil was extracted from the aerial parts of P. crispa through hydro-distillation using a Clevenger-type apparatus, and it was analyzed with GC-MS. The most dominant chemical constituents of the essential oil were sesquiterpenes (78.26%). The higher constituents were β-caryophyllene oxide (33.97%), modephene (23.34%), geranyl propionate (6.32%), geranyl isovalerate (6.74%), 4-cadinadiene (5%), humulene (4.05%), and β-caryophyllene (2.73%). The essential oil exhibited DPPH radical activity, and it exerted antibacterial effect against gram positive bacteria (Staphylococcus aureus and methicillin-resistant Staphylococcus aureus. However, it had no antibacterial effect on gram negative bacteria (Pseudomonas aeruginosa, Shigella sonnei, Klebsiella pneumoniae and Escherichia coli). The P. crispa essential oil produced significant cytotoxic effects against Hep-G2, MCF-7, Coca-2, and HT-29 ?cells. The oil was most toxic to Hep-G2 cells, based on its IC₂₀ and IC₅₀ values. These results indicate that the essential oil from P. crispa has potent biological properties which can be useful in the food and pharmaceutical industries.     

Ternary and binary copper(II) complexes: synthesis,characterization, ROS-inductive,proteasome inhibitory,and anticancer properties

Three ternary copper(II) complexes, [Cu(phen)(L-phe)Cl]·2H₂O, [Cu(phen)(L-leu)Cl]·4½H₂O, and [Cu(phen)(L-tyr)Cl]·3H₂O, and four binary copper(II) complexes, [Cu(phen)Cl₂]_, Cu(L-phe)₂·½H₂O, Cu(L-leu)₂·½H₂O, and Cu(L-tyr)₂·H₂O (where phen = 110-phenanthroline, L-phe = L-phenylalanine, L-tyr = L-tyrosine, L-leu = L-leucine and Cl^- = chloride), were synthesized and characterized by elemental analysis, spectroscopic techniques (FTIR, UV–visible, fluorescence spectroscopy), magnetic susceptibility, molar conductivity, and lipophilicity measurement. X-ray diffraction determination of a single crystal of [Cu(phen)(L-tyr)Cl] showed two independent molecules in the asymmetric unit, each with the same distorted square pyramidal geometry about copper(II). p-Nitrosodimethylaniline assay revealed that the three ternary complexes were better inducers of reactive oxygen species over time than binary complexes, CuCl₂, and free ligands. All the copper(II) complexes in this series inhibited the three proteolytic activities in the order Trypsin-like > Caspase-like > Chymotrypsin-like. In terms of anticancer properties, the copper(II)-phen complexes had GI50 values of less than 4 μM against MCF-7, HepG2, CNE1 and A549 cancer cell lines, more potent than cisplatin.     

Design,synthesis and evaluation of the antioxidant and neuroprotective properties of alkyl- and terpenylphenolchlorin conjugates

The new amide conjugates were synthesized from methyl pheophorbide a and its carboxyl derivatives by reactions with aminomethyl derivatives of 2,4-dimethylphenol, 2-isocamphyl-4- methylphenol, 2-bornyl-4-methylphenol, and 2-isobornyl-4-methylphenol. The antioxidant activity of some conjugates was established by investigation of their ability to inhibit the accumulation of secondary products of lipid peroxidation in a brain of laboratory mice in vitro. The neuroprotective properties of porphyrin and terpenylphenol conjugates have been studied on the model of H₂O₂-induced oxidative stress in SH-SY5Y cells (neuroblastoma).

     

Synthesis and evaluation of the catalytic properties of semicarbazides derived from N-triphenylmethyl-aziridine-2-carbohydrazides

A straightforward synthesis of a series of new catalysts derived from N-triphenylmethyl-aziridine-2-carbohydrazides is described. The new compounds have been tested for the enantioselective addition of diethyl- and phenylethynylzinc to aryl and alkyl aldehydes, which afforded the corresponding chiral alcohols in high chemical yields (up to 92%) and with excellent ee’s of approximately 90%.     

Eco-friendly synthesis of ZnO nanorods using Cycas pschannae plant extract with excellent photocatalytic,antioxidant, and anticancer nanomedicine for lung cancer treatment

The tunable ZnO nanorods (NRs) are produced due to the phytochemicals present in Cycas pschannae leaves which act as reducing and stabilizing agents. The confirmations of the ZnO NRs were validated using different characterization techniques: X-ray diffraction, Fourier transform infrared spectroscopy, Brunauer, Emmett and Teller (BET), scanning electron microscopy–Energy Dispersive X-Ray Analysis (EDX), UV–visible spectroscopy, Raman spectroscopy, and transmission electron microscopy. The ZnO NRs show unique surface area and low particle size. Photocatalytic activity was measured and found to be 50.75% at low concentrations and 78.33% at high concentrations. The antioxidant activity of the ZnO NRs also showed promising results for their use in free radical scavenging. In vitro toxicity studies using zebrafish embryos was performed to evaluate the toxic nature of it and the obtained result confirmed its non-toxic nature. In addition, ZnO anticancer potential was verified using the A549 lung cancer cell line. Cytotoxic assessments of ZnO NRs were performed via 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), and neutral red uptake assays to examine the cell death cycle on the A549 lung cancer cell. Dose-dependent apoptosis and necrosis were confirmed by Lactate dehydrogenase (LDH) assay. It was also confirmed that ZnO NRs induce Reactive oxygen species (ROS) and apoptosis inside cancer (A549) cells via different intrinsic gene expression. Thus, based on this research it is evident that an effective ecofriendly, nontoxic potential anticancer drug can be synthesized using C. pschannae leaf extract.     

Solvent-free one-pot synthesis of polysubstituted tetrahydropyrimidines and their antioxidant and antimicrobial properties

Research on Chemical Intermediates - A versatile and highly efficient one-pot multicomponent approach for the synthesis of novel multisubstituted tetrahydropyrimidine...