Substituted Phenacyl Bromides Research Articles

Discovery of new fenamate-based derivatives as anticancer agents and potent VEGFR-2 inhibitors

VEGFR-2 is a critical target for the treatment of solid tumors. This work represents synthetic approaches to a new class of fenamate-based derivatives with essential pharmacophoric properties comparable to VEGFR-2 inhibitors. The reaction of tolfenamic acid hydrazide with substituted phenacyl bromide, and phenylisothiocynate derivatives produced novel tolfenamic acid (TA) derivatives (compounds 4 and 5). The target molecules were validated using spectroscopic techniques such as FT-IR and 1HNMR. Docking tests were performed to determine how the synthesized chemicals bind to the putative molecular target, VEGFR-2. The docking results demonstrated that the synthesized compounds could bind VEGFR-2 correctly. Finally, computational physicochemical analysis of the most active candidates revealed that they have favorable assets and reasonable drug-likeness reports.

Evaluation of synthetic 2-aryl quinoxaline derivatives as α-amylase, α-glucosidase, acetylcholinesterase, and butyrylcholinesterase inhibitors

Variety of 2-aryl quinoxaline derivatives 1–23 were synthesized in good yields, by reacting 1,2-phenylenediamine with varyingly substituted phenacyl bromides in the presence of pyridine catalyst. All molecules 1–23 were characterized by spectroscopic techniques and evaluated for their diverse biological potential against α-amylase (α-AMY), α-glucosidase (α-GLU), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes. Synthetic derivatives possess enhanced inhibitory potential against all enzymes at nanomolar concentrations. In particular, compound 14 was found much superior with IC50 = 294.35, 198.21, 17.04, and 21.46 nM against α-AMY, α-GLU, AChE, and BChE, respectively, as compared to standard inhibitors. Furthermore, selected potent compounds, including 3, 4, 8, 14, 15, 17, and 18, were subjected to molecular docking studies to decipher the binding energies and interactions of ligands (synthetic molecules) with all four target enzymes.

A Facile One-Pot, Three-Component Synthesis of a New Series of Thiazolyl Pyrazoles: Anticancer Evaluation, ADME and Molecular Docking Studies

A series of thiazolyl pyrazoles (4a–f, 6a–f, and 8a–b) were synthesized by a conventional method using thiosemicarbazide, substituted phenacyl bromides, or substituted 3-(2-bromoacetyl) coumarins, 1-Boc-3-cyano-4-pyrrolidone, or 1-Boc-3-cyano-4-piperidone. All synthesized compounds' structures were confirmed by spectral (1H- and 13C-NMR, FTIR, Mass) and analytical data. The target compounds were screened for their in vitro anticancer activity. The results found that the compound 8a and 8b has shown significant antiproliferative activity against HeLa, A549, and MDA-MB-231 cancer lines. Furthermore, in silico ADME profiles were also predicted to set effective lead candidates for future anticancer drug discovery initiatives. The synthesized thiazolyl pyrazoles derivatives were further subjected to docking simulations, and the results were in agreement with the in vitro results.

Convenient multicomponent synthesis of furo[3,2-c]coumarins in the promoting medium DIPEAc and assessment of their therapeutic potential through in silico pharmacophore based target screening

A one-pot three-component approach for the synthesis of dihydrofuro[3,2-c]coumarins was developed via the reaction of aryl/hetryl aldehydes, substituted phenacyl bromides and 4-hydroxycoumarin using N,N-diisopropyl ethyl ammonium acetate as the promoting medium.

Eco-friendly Synthesis of Some New Benzylidene-iminothiazolyl-pyrazol-3-ol Derivatives via One-Pot Multicomponent Reaction and Evaluation of Antioxidant Activities

In present work, one-pot multicomponent reaction (MCR) route for the synthesis of benzylideneiminothiazolyl- pyrazol-3-ol derivatives (5a-p) by reacting ethyl cyanoacetate (1), substituted benzaldehyde (2a-c), thiosemicarbazide (3) and substituted phenacyl bromide (4a-g). This reaction proceeds by using bleaching earth clay (BEC) (pH 12.5) in PEG-400 as a green reaction media. All the synthesized compounds were characterized by IR, 1H NMR, 13C NMR and mass spectral data. The pharmacological investigation of the synthesized compounds suggest that most of them showed good antioxidant activity.

Synthesis and antibacterial activity of 3-arylaminomethyl-1-(2-oxo-2-arylethyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a] azepin-1-ium bromides and aryl-(4-R1-phenyl-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[cd]azulen-1-ylmethyl)-amines

The aim of this work is to develop methods of synthesis of 3-arylaminomethyl-1-(2-oxo-2-arylethyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-1-ium bromides and aryl-(4-R1-phenyl-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[cd]azulen-1-ylmethyl)-amines and to study their antimicrobial activity against strains of gram-positive and gram-negative bacteria as well as yeast fungi.
 Materials and methods. 1Н NMR spectra were recorded on Bruker 400 spectrometer operating at frequency of 400 MHz. Antimicrobial activity of the compounds synthesized was evaluated by their minimum inhibitory concentration (MIC) values.
 Results and discussion. The interaction of 3-arylaminomethyl-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepines with substituted phenacyl bromides produced novel 3-arylaminomethyl-1-(2-oxo-2-arylethyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-1-ium bromides. The latter when refluxed in 10 % solution of NaOH gave aryl-(4-R1-phenyl-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[cd]azulen-1-ylmethyl)-amines. The study of antimicrobial activity of the compounds obtained allowed to find derivatives which are active against С. albicans and S. aureus strains. Among the compounds tested 3-[(41-bromophenylamino)-methyl]-1-[2-(4-methoxyphenyl)-2-oxoethyl]-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-1-ium bromide 5cd appeared to be more active than the reference drug Cefixime and displayed close antimicrobial activity as the antibiotic Linezolid.
 Conclusions. It was found out that derivatives of 3-arylaminomethyl-1-(2-oxo-2-arylethyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-1-ium bromides display broad spectrum of antimicrobial activity and are able to inhibit growth of both bacteria and fungi. S. aureus and C. albicans turned out to be the most sensitive strains to the compounds tested, MIC was in the range of 6.2-25.0 mg/mL. Gram-negative strains of microorganisms were less sensitive to the compounds evaluated and 5fа was the most active derivative displaying antimicrobial activity at the concentration of 50.0 mg/mL. Antimicrobial activity of triazoloazepinium bromide derivatives was similar to that one of Linezolid and Fluconazole reference drugs and more pronounced than the activity of Cefixime.
 Hence, the data gathered evidence the feasibility of further study of the antimicrobial properties of the most active compounds in in vivo experiments aiming at assessment of the prospects for the creation of new effective and safe antimicrobial drugs based on them

Graphene Oxide Pickering Emulsion – A Novel Reaction Medium for the Synthesis of 2‐Aminothiazole

AbstractIn the present study, a novel protocol for the synthesis of 2‐aminothiazoles has been developed using a graphene oxide (GO) stabilized Pickering emulsion system. GO was prepared by the modified Hummer's method and characterized with XRD, FTIR, UV‐Visible spectroscopy, TGA and DLS techniques. The size of the o/w emulsion droplets stabilized by GO were determined using a polarized optical microscope. The emulsion system was used for the synthesis of 2‐aminothiazole by Hantzsch reaction. The Reactions were carried out at room temperature and under static condition, without stirring. The application of the reaction system were extended to substituted phenacyl bromides and about 93 % of the corresponding 2‐aminothiazole derivative was obtained in 3 h.

Yttrium(III) oxide catalyzed facile synthesis of novel hydrazinyl thiazoles by multicomponent approach

A facile and a one-pot procedure for the synthesis of novel hydrazinyl thiazoles by the cyclo condensation reaction between substituted phenacyl bromides, aromatic aldehydes, and semicarbazides using Yttrium(III) oxide as reusable catalyst under acetic acid as a solvent medium is described. The chromatography-free methodology has several benefits such as being facile, atom economic, higher functional group tolerance and provides excellent yield in shorter reaction time. All the synthesized compounds were characterized by 1H NMR, 13C NMR, and HRMS (ESI) analysis.

Silica supported dodecatungstophosphoric acid (DTP/SiO2): An efficient and recyclable heterogeneous catalyst for rapid synthesis of quinoxalines

A facile synthesis of quinoxalines by the cyclocondensation of substituted phenacyl bromides with o-pheneylenediamines using silica-supported dodecatungstophosphoric acid (DTP/SiO2) as a recyclable heterogeneous catalyst is unveiled in this research work. This method is practicable due to environmentally benign, easy workup, high yield, less reaction time, low cost, mild reaction condition, and recyclable heterogeneous catalyst. The catalyst can be easily recovered from the reaction mixture only by filtration and reused up to five catalytic cycles without significant loss of catalytic activity and product yield. This leads to making the process more affordable.

Synthesis and Anticonvulsant activity of new 5-((1-(2-(4-substituted phenacyl bromide)-2-oxoethyl)-2-phenyl-1H-indol-3yl) methylene) pyrimidine-2, 4, 6(1H, 3H, 5H)-trione Derivatives

In the current scenario we have plant to study to synthesize novel indole derivatives (4a-d) and (5a-b) which have the target activity like anti-convulsion and anti microbial etc. In the primary phase, we synthesized 2-phenyl-1H-indole reacted with Phosphorus oxychloride and N, N’-dimethylformamide by using vilsmeier reagent formylation of a new compound 2-phenylindole-3-carbaldehyde (2). The 2-phenylindole-3-carbaldehyde was reacted with substituted phenacyl bromide, K2CO3 and TBAB (Tetra butyl ammonium bromide) into the presence of N, N’-dimethylformamide to gives [1-(2-(4-substituted phenacyl bromide)-2-oxoethyl)-2-phenylindole-3-carbaldehyde (3a-d). The compound [1-(2-(4- substituted phenacyl bromide)-2-oxo-ethyl)-2-phenylindole-3-carbaldehyde was permitted to mixed with various substituted phenacyl bromide gives corresponding indole derivatives. The indole derivatives (3a-d) were reacted with barbituric acid and thiobarbituric acid dissolved into the methanol at reflux for 4h to gives afforded compounds (4a-d) and (5a-b). The final indole barbituric derivatives (4a-d) and (5a-b) were synthesized from substituted phenacyl bromide by the react with methanol and recrystalized from ethanol. The last compound has been completed on the basis of spectra FT-IR and 1H NMR. All the value of FT-IR, 1H NMR, Solubility and TLC were considered to be prominent. The pharmacological screening through ear electrode induced current 50mA for 0.2 seconds in electro-convulsiometer for anticonvulsant activity. The synthesize compounds were establish to be 4b, 4c, 4d, and 5a. The compound 4c and 5a were established to be the most potent compound through compare to standard drugs phenytoin sodium.

A facile one-pot, three-component synthesis of a new series of thiazolyl pyrazole carbaldehydes: In vitro anticancer evaluation, in silico ADME/T, and molecular docking studies

A series of thiazolyl pyrazole carbaldehydes (4a-n) were synthesized by conventional method using thiosemicarbazide, substituted phenacyl bromides, substituted 3-acetylcoumarins, and Vilsmeyer-Hack reagent. Structures of all the synthesized compounds were confirmed by spectral (1H & 13C NMR, FTIR, Mass) and analytical data. The target compounds were screened for their in vitro anticancer activity. From the results, it was found that the compound 4m has shown significant antiproliferative activity against all tested cell-lines. Furthermore, in silico ADME/T profiles were also carried out to set effective lead candidates for the future anticancer drug discovery initiatives. Molecular docking studies were carried out against colchicine binding site of β-tubulin and the results were in concordance with the in vitro anticancer data.

A facile one-pot, three component synthesis of a new series of 1,3,4-thiadiazines: Anticancer evaluation and molecular docking studies

A series of new 1,3,4-thiadiazines were synthesized by the conventional method of dehydroacetic acid, thiocarbohydrazide and substituted phenacyl bromides or substituted 3-(2-bromoacetyl) coumarins. Structures of all the synthesized compounds were confirmed by spectral (1H &13C NMR, FTIR, Mass) and analytical data. The target compounds were screened for their in vitro anticancer activity, From the in vitro anticancer results, it was found that the compound 6a has shown significant activity with the standard. Furthermore, the synthesized 1,3,4-thiadiazines were inflicted to molecular docking simulations for gaining insights into their mechanism of action and possible mode of binding against STAT3. The docking results were consistent with the experimental data.

Synthesis of Imidazo [1, 2-a] Pyridine Derivatives Using Copper Silicate as an Efficient and Reusable Catalyst

Synthesis of imidazo [1, 2-a] pyridines derivatives were reported from 2-aminopyridine and various substituted phenacyl bromide using copper silicate as an efficient, eco-friendly, and reusable catalyst. The present protocol offers various advantages, such as the use of less hazardous solvent, high yield, and operationally simple procedure.

Synthesis of Furoneoflavones Modified by Coumarin and (HET)Aroyl Substituents

Furo[3,2-g]neoflavones and furo[2,3-h]neoflavones modified by coumarin and (het)aroyl substituents were synthesized via reactions of 7-hydroxy-6(8)-acetyl(formyl)neoflavones with substituted phenacyl bromides, 2-bromacetylbenzofuran, and 4-chloromethylcoumarins.

Synthesis, Docking Study And In Vitro Anticancer Evaluation Of New Derivatives Of 2-(1-(2-Flouro-[1,1-Biphenyl]-4-Yl)Ethyl)-6-(Substituted Phenyl) Imidazole[2,1-B][1,3,4]Thiadiazole Derived From Flurbiprofen

Objectives: New derivatives of 2-(1-(2-flouro-[1,1-biphenyl]-4-yl)ethyl)-6-(substituted phenyl) imidazole[2,1-b][1,3,4]thiadiazole, compounds(2-5), were designed and synthesized from the starting parent molecule, flurbiprofen. Materials and Methods: Compound (1) was synthesized by refluxing flurbiprofen, as a starting material , with phosphorus oxychloride (POCl3), and thiosemicarbazide, resulting in flurbiprofen -1,3,4 thiadiazole -2 amine derivative. The target compounds(2-5) were obtained by refluxing compound(1) with different substituted phenacyl bromides, Results: The new compounds were characterized by FTIR, 1HNMRs and CHNS analysis. A molecular docking study of the synthesized compounds (2-5) against HIV protease indicated such compounds occupied the critical site of HIV protease pocket, and demonstrated excellent positioning of the compounds in the pocket. The best binding energy values were (-7.49, -7.22 , -7.51 and-7.12 kcal/mol) for the compounds (2 -5(, respectively. The anticipated physio-chemical parameters(calculated logarithmic of partition cofficent(Clog p),molecular volume (MV), number of violations (nviol), topological surface area (TPSA), and percent of absorption(%Abs.) were computed using software Molinspiration. In vitro outcomes, the target compounds were assessed by cell line study for their anticancer effects. All the tested compounds showed the most plausible anticancer activity, when compared to a positive control (atazanavir), using MTT cytotoxic assay, against human prostatic tumor (PC-3), glioma cell line (LN68), and normal WRL-68 cell line. Conclusion: The results revealed that compounds 2,3,4 and 5 exhibited the highest inhibitory activity against PC3 cell line at IC50 concentrations of 178.2, 75.09, 129.3and 110.5μg/mL, respectively, and they had moderate effects against LN299 cell line at IC50 concentrations 203,172.5, 169,and 157.7 μg/mL, respectively, compared to atazanavir, as a positive control against PC-3, at IC50, 157.3 μg/mL, and in LN299, at IC50 195.7 μg/mL. Also compound (5) attributed to cell-cycle arrest, and induction of apoptosis. The target compounds could be considered as promising as potential anticancer drugs.

A SIMPLE SYNTHESIS, OF SOME NOVEL BI-THIAZOLES AS ANTI-TUMOR AGENTS

Revised Abstract A series of novel bi-thiazoles was synthesized by reaction of 2-(1-(2-(2-(1-(4-fluorophenyl)ethylidene)hydrazinyl)-4-methylthiazol-5-yl)ethylidene) hydrazine-1-carbothioamide 3 with a variety of hydrazonoyl chloride derivatives 4a-d, and 7 a-d affording 6a-d and 9a-d respectively in dioxane in the presence of triethyl amine as a base. Also, hydrazine-1-carbothioamide 3 reacts with substituted phenacyl bromide derivatives 10 a-d yielding 12a-d in appropriate reaction conditions. The mechanisms of the titled reactions were discussed. Structural assignments were based on spectroscopic methods (NMR, FTIR, MS). The new compounds were tested in vitro for their were subjected to in vitro anticancer screening against human hepatocellular carcinoma (HCT-116), (HepG-2) and the results showed that compounds 6a, 6d, 9a, 9c and 12a have promising activities compared with cisplatin reference drug.

Potent α-amylase inhibitors and radical (DPPH and ABTS) scavengers based on benzofuran-2-yl(phenyl)methanone derivatives: Syntheses, in vitro, kinetics, and in silico studies

Thirty benzofuran-2-yl(phenyl)methanones 1–30 were synthesized and characterized their structures by spectroscopic techniques. Substituted phenacyl bromide and different derivatives of 2-hydroxy-benzaldehyde treated in the presence of anhydrous K2CO3 in acetonitrile at room temperature to afford the desired benzofurans 1–30. All compounds were screened for their in vitro α-amylase inhibitory and radical scavenging (DPPH and ABTS) activities. Results revealed that para substituted compounds were found to be more active than the others with IC50 values ranges for α-amylase inhibition (IC50 = 18.04–48.33 µM), DPPH (IC50 = 16.04–32.33 µM) and ABTS (IC50 = 16.99–33.01 µM) radical scavenging activities. Activities results were compared with the standards acarbose (IC50 = 16.08 ± 0.07 µM) for α-amylase, ascorbic acid (IC50 = 15.08 ± 0.03 and 15.09 ± 0.17 µM) for DPPH and ABTS radical scavenging activities, respectively. Kinetic studies predicted that all compounds followed non-competitive mechanism of inhibition. Molecular docking results showed good protein–ligand interactions profile against the corresponding target. To the best of our knowledge, out of thirty molecules, ten compounds 18–20, 22, and 25–30 were structurally new.

Design and synthesis of new thiazoles by microwave-assisted method: Evaluation as an anti-breast cancer agents and molecular docking studies

A series of novel thiazole analogues were designed and synthesized by the microwave-assisted multicomponent reaction of thiocarbohydrazide, aldehydes with substituted phenacyl bromides. Structures of all the synthesized compounds were in good agreement with their spectral (1H and 13C NMR, FTIR, Mass) and analytical data. The target thiazole compounds were screened for their in vitro cytotoxic activity by testing against MCF-7, MDA-MB-231/ATCC, HS 578 T, BT-549, T-47D and MDA-MB-468 Breast cancer cell lines. From the in vitro results, it was found that the compound 4b has potent activity against MDA-MB-231/ATCC cell line. Docking studies were also done on these compounds to probe the possible binding site interactions which corroborated well with the in vitro results.

Synthesis, characterization, antibacterial and DNA photocleavage study of 1-(2-Arenethyl)-3, 5-dimethyl-1H-pyrazoles

Abstract 1-(2-Arenethyl)-3, 5-dimethyl-1H-pyrazoles (4a-g) were obtained by Wolff-Kishner reduction of 2-(3,5-Dimethyl-1H-pyrazol-1-yl)-1-arylethanones (3a-g). The synthesized compounds were characterized by analyzing their IR, 1H, and 13C-NMR spectral data. Intermediates (3a-g) were synthesized by the solid phase reaction of 3, 5-dimethylpyrazole with different substituted phenacyl bromides under basic condition by adopting reported procedure. All synthesized compounds were screened in vitro for their anti-bacterial potential against four bacterial strains and it was found that the compounds 4c and 4g bearing methoxy and nitro group, respectively, exhibited good level of inhibitory potential which was about 25% of the standard drug, Ciprofloxacin- against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa bacterial strains. Further, DNA photocleavage ability was also explored and it was observed that compounds bearing halogen group (4d, 4e and 4f) displayed good DNA photocleavage activity.

A Three Component Protocol for the Synthesis of Aziridines using BF3·(OEt)2

Synthesis of N-(1R,2S)-2-(bromo-3-oxo-1,3-diphenylpropyl)-4-methylbenzene sulfonamide and N-(1R,2S)-(2-bromo-3-oxo-1,3-diphenylpropyl)-4-methylbenzene sulfonamide was carried out by a three component reaction using phenacyl bromide, p-toluenesulfonamide and carboxyaldehyde in presence of mild Lewis acid such as BF3·(OEt)2 in dichloromethane. The synthetic utility of this protocol was carried out with syn-isomer to yield corresponding cis-aziridines. This protocol was operationally simple for a wide variety of substituted carboxaldehydes and substituted phenacyl bromides.