- Design, synthesis and neuropharmacological evaluation of new 2,4-disubstituted-1,5-benzodiazepines as CNS active agents
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Benzodiazepines (BZDs) represent a class of privilege scaffold in the modern era of medicinal chemistry as CNS active agents and BZD based drugs are used to treat different psychotic disorders. Inspired from the therapeutic potential of BZDs as promising CNS active agents, in the present work three different series of 1,5-benzodiazepines bearing various substitutions at position 2 and 4 of the benzodiazepine core were synthesized by condensing different substituted chalcones with o-phenylenediamine in the presence of piperidine as a base catalyst. Structural characterization of title compounds was done by using various analytical techniques such as IR, NMR, elemental analysis and mass spectral data. All the synthesized compounds (9a-d, 10a-e and 11a-c) were subjected to in vivo neuropharmacological studies to evaluate their CNS depressant and antiepileptic activity. Results of in vivo evaluation data showed that analogue 11b exhibited potent CNS depressant activity which was comparable to the standard drug diazepam. Compounds 10b and 10c displayed significant antiepileptic activity however they were less potent than the standard drug phenobarbitone. Molecular docking studies were performed using MOE software to find the interaction pattern and binding mode at the GABAA receptor (PDB Id: 6HUP). The results of the docking studies were in good agreement with the observed in vivo activity and revealed the satisfactory binding mode of the compounds within the binding site of the protein. The docking scores for the most promising candidates 10c, 11b and Diazepam were found to be ?9.18, ?9.46 and ?9.88, respectively. Further, the compounds showed compliance with the Lipinski's ‘rule of five’ and exhibited favourable drug-likeness scores. The identified leads can be explored further for the design and development of new BZD based psychotropic agents.
- Bhatia, Rohit,Kumar, Bhupinder,Mehan, Sidharth,Monga, Vikramdeep,Singh, Gurpreet,Verma, Ramesh
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- SAR and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogs
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The present study describes the synthesis of a series of 22 chalcone analogs. These compounds were evaluated as potential human MAO-A and MAO-B inhibitors. The compounds showed varied selectivity against the two isoforms. The IC50 values were f
- Shalaby, Raed,Petzer, Jacobus P.,Petzer, Anél,Ashraf, Usman M.,Atari, Ealla,Alasmari, Fawaz,Kumarasamy, Sivarajan,Sari, Youssef,Khalil, Ashraf
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- Solvent free synthesis of 1,3-diaryl-2-propenones catalyzed by commercial acid-clays under ultrasound irradiation
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This paper presents a novel solvent free method of synthesis of trans-chalcones. The method was based on ultrasound irradiation of the reagents (aryl methyl ketones and aryl aldehydes) in presence of commercial acid-montmorillonites as catalysts. The trans-chalcones were synthesized in high yields (85-95%) and excellent selectivity in a short reaction time.
- Chtourou, Manef,Abdelhédi, Rami,Frikha, Mohamed Hédi,Trabelsi, Mahmoud
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- One-pot synthesis of α,β-unsaturated ketones
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The preparation of α,β-unsaturated ketones is performed in a one-pot procedure by subsequent treatment of diethyl lithiomethylphosphonate with nitriles, followed by addition of carbonyl compounds and hydrolysis.
- Lee,Oh
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- Novel potent and selective DPP-4 inhibitors: Design, synthesis and molecular docking study of dihydropyrimidine phthalimide hybrids
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Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as antihyperglycemic agents that improve glycemic control in type 2 diabetic patients, either as monotherapy or in combination with other antidiabetic drugs. Methods: A novel series of dihydropyrimidine phthalimide hybrids was synthesized and evaluated for their in vitro and in vivo DPP-4 inhibition activity and selectivity using alogliptin as reference. Oral glucose tolerance test was assessed in type 2 diabetic rats after chronic treatment with the synthesized hybrids ± metformin. Cytotoxicity and antioxidant assays were performed. Additionally, molecular docking study with DPP-4 and structure activity relationship of the novel hybrids were also studied. Results: Among the synthesized hybrids, 10g, 10i, 10e, 10d and 10b had stronger in vitro DPP-4 inhibitory activity than alogliptin. Moreover, an in vivo DPP-4 inhibition assay revealed that 10g and 10i have the strongest and the most extended blood DPP-4 inhibitory activity compared to alogliptin. In type 2 diabetic rats, hybrids 10g, 10i and 10e exhibited better glycemic control than alogliptin, an effect that further supported by metformin combination. Finally, 10j, 10e, 10h and 10d had the highest radical scavenging activity in DPPH assay. Conclusions: Hybrids 10g, 10i and 10e are potent DPP-4 inhibitors which may be beneficial for T2DM treatment.
- Mourad, Ahmed A. E.,Khodir, Ahmed E.,Saber, Sameh,Mourad, Mai A. E.
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- An improved synthesis of pyrido[2,3-: D] pyrimidin-4(1 H)-ones and their antimicrobial activity
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The screening of a small library of diverse chemical structures resulted in the identification of 2-thioxodihydropyrido[2,3-d]pyrimidine 10a as having broad spectrum antibacterial activity (MIC 0.49-3.9 μg mL-1), and reasonable antifungal activity (MIC 31.25 μg mL-1). An expeditious synthesis of 10a was optimized by varying solvents, catalysts and the use of microwave irradiation with the best conditions using DMF as a solvent, I2 (10 mol%) and a 30 minutes reaction time compared to 15 h for classic conventional heating. The pharmacokinetic properties and calculation of drug likeness of 10a suggested good traditional drug-like properties and led to the synthesis of a small library with seven compounds 10a and 10d-i showing broad antimicrobial activity (MIC = 0.49-7.81 μg mL-1) and selectivity indices of more than 5.6 against the normal colon cell line (CCD-33Co). The antifungal activity of compounds 10d-i was moderate to strong with MIC values of 1.95-15.63 μg mL-1.
- Fares, Mohamed,Abd El Hadi, Soha R.,Eladwy, Radwa A.,Shoun, Aly A.,Abdel-Aziz, Marwa M.,Eldehna, Wagdy M.,Abdel-Aziz, Hatem A.,Keller, Paul A.
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supporting information
p. 3389 - 3395
(2018/05/23)
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- Microwave-irradiated synthesis and biological evaluation of 3,5-diaryl-1-phenyl-2-pyrazolines as antibacterial and anti-inflammatory agents
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In a wide search program towards a biologically active antibacterial and anti-inflammatory agents, a series of 3,5-diaryl-1-phenyl-2-pyrazoline have been synthesized with excellent yields employing microwave techniques starting from substituted α,β-unsaturated carbonyl compounds which undergo cyclization reactions with phenylhydrazine. The structures of newly synthesized compounds were characterized and confirmed on the basis of FT-IR, 1H NMR and mass spectral analyses. The synthesized compounds 3,5-diaryl-1-phenyl-2-pyrazolines had shown significant activity against Staphylococcus aureus (MTCC 87), Escherichia coli (MTCC 40), Pseudomonas aeruginosa (MTCC 424) and Proteus vulgaris (MTCC 426) by cup plate method using tetracycline-SD 037 as a reference standard. The anti-inflammatory property of 1,3,5-diaryl-1-phenyl-2-pyrazolines were screened by using carragenan induced paw edema method in Wistar rat. The anti-inflammatory activities were comparable to that of the standard drug diclofenac. The safety of 3,5-diaryl-1-phenyl-2-pyrazolines were reflected by toxicity studies.
- Kumar, Anjan,Rout, Sradhasini,Panda, Jnyanaranjan,Sahoo, Biswa Mohan,Banik, Bimal Krishna
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p. 1321 - 1326
(2020/06/27)
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- Monoamine Oxidase Inhibitory Activity: Methyl- versus Chlorochalcone Derivatives
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Numerous studies have shown that chalcones are promising scaffolds for the development of new monoamine oxidase-B (MAO-B) inhibitors. As a continuation of our ongoing research into the development of reversible human MAO-B (hMAO-B) inhibitors, two series
- Mathew, Bijo,U?ar, Gülberk,Mathew, Githa Elizabeth,Mathew, Sincy,Kalatharakkal Purapurath, Praseedha,Moolayil, Fasil,Mohan, Smrithy,Varghese Gupta, Sheeba
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p. 2649 - 2655
(2016/12/23)
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- Effects of structural and electronic characteristics of chalcones on the activation of peroxisome proliferator-activated receptor gamma
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Chalcones share some structural similarities with GW-1929, a highly-selective and potent agonist for peroxisome proliferator-activated receptor-gamma (PPARγ). In this study, we tested 53 structurally diverse chalcones to identify characteristics essential for PPARγ activation in a GAL4-based transactivation assay. This screen identified several novel chalcone agonists of PPARγ. Our results indicate that chalcones with an electron rich group or sterically large groups such as naphthyl on the carbonyl side tend to activate PPARγ. The absence of any strict structural or electronic requirements suggests that the flexibility of the PPARγ ligand binding pocket may allow binding of diverse chalcones with some preference for a slightly larger electron-rich group on the carbonyl side. We predict that further structure-activity relationship studies on chalcones with naphthalene or electron-rich groups near the carbonyl moiety will lead to the development of more potent PPARγ agonists.
- Schott, Jason Taylor,Mordaunt, Charles Edward,Vargas, Anthony Joseph,Leon, Martin Antonio,Chen, Kevin Hsinwen,Singh, Mandeep,Satoh, Mikiko,Cardenas, Emilio Leal,Maitra, Santanu,Patel, Nilay Vinod,De Lijser, Hubrecht Johan Peter
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p. 229 - 236
(2013/03/14)
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- Two expedient 'one-pot' methods for synthesis of β-aryl-β- mercaptoketones over anhydrous potassium carbonate or amberlyst-15 catalyst
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Two expedient one-pot methods have been developed for synthesis of β-aryl-β-mercaptoketones using acetophenones, benzaldehydes and thiols as starting materials. The methods involve microwave irradiation (5min) of 1:1 mixtures of acetophenones and benzaldehydes over neutral alumina supported anhydrous potassium carbonate or amberlyst-15 in the first step, and that is followed by addition of thiol to the resulting material and keeping at room temperature for 1.5 h. Indian Academy of Sciences.
- Guha, Chayan,Mondal, Rina,Pal, Rammohan,Mallik, Asok K.
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p. 1463 - 1470
(2014/04/03)
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- Synthesis and in vitro evaluation of novel tetrazole embedded 1,3,5-trisubstituted pyrazoline derivatives as Entamoeba histolytica growth inhibitors
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A series of pyrazoline derivatives (1a-15a) was synthesized by cyclization of chalcones (1-15) with 2-[5-(4-methoxyphenyl)-1H-tetrazol-1-yl]acetohydrazide under basic conditions and were screened in vitro, to find out effect on the growth of HM1: IMSS strain of Entamoeba histolytica. The compounds 3a, 4a, 11a, 13a and 14a showed encouraging results with IC50 value in the range of 0.86-1.28 μM. However compound 13a showed most promising results with IC50 = 0.86 μM which is half of the metronidazole, the standard drug used for protozoal infection. Cell viability test in human hepatocellular carcinoma cell line (HepG2) revealed non-toxic nature of new synthesized compounds. Safety index calculations prevailed compound 13a as highly antiamoebic and least cytotoxic (S.I. = >116.28), almost twice than metronidazole.
- Wani, Mohmmad Younus,Bhat, Abdul Roouf,Azam, Amir,Lee, Dae Hyung,Choi, Inho,Athar, Fareeda
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experimental part
p. 845 - 854
(2012/09/11)
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- Design, Synthesis, Antibacterial Activity, and Molecular Docking Studies of Novel Hybrid 1,3-Thiazine-1,3,5-Triazine Derivatives as Potential Bacterial Translation Inhibitor
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Some novel hybrid 1,3-thiazine-1,3,5-triazine derivatives were synthesized and tested for antibacterial activity. Compounds 8c and 8f were found active against Gram positive and Gram negative microorganisms. Molecular docking studies have been performed o
- Singh, Udaya P.,Pathak, Manish,Dubey, Vaibhav,Bhat, Hans R.,Gahtori, Prashant,Singh, Ramendra K.
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p. 572 - 583,12
(2020/07/31)
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- Evaluation of new chalcone derivatives as polyphenol oxidase inhibitors
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A newly series of 4-(phenylurenyl)chalcone (4a-j) and 4′- (phenylurenyl/thiourenyl)chalcone (9a-l) derivatives were synthesized and their inhibitory effects on the diphenolase activity of banana tyrosinase were evaluated. Tyrosinase has been purified from banana on an affinity gel comprised of Sepharose 4B-l-tyrosine-p-aminobenzoic acid. The result showed that 4a-j inhibited the PPO enzyme activity. Conversely, 9a-h and 9i-l showed activator effect on tyrosinase enzyme activity.
- Sonmez, Fatih,Sevmezler, Sedat,Atahan, Alparslan,Ceylan, Mustafa,Demir, Dudu,Gencer, Nahit,Arslan, Oktay,Kucukislamoglu, Mustafa
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supporting information; experimental part
p. 7479 - 7482
(2012/02/04)
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- KF-melamine formaldehyde resin (KF-MFR) as a versatile and efficient heterogeneous reagent for aldol condensation of aldehydes and ketones under microwave irradiation
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KF-Melamine formaldehyde resin (KF-MFR) was demonstrated to be a highly efficient heterogenious catalyst for cross-aldol condensation under microwave irradiation. In this synthesis, various aldehydes and ketones were condensed together in the presence of supported KF on melamine-formaldehyde resin to afford different chalcone derivatives in good to excellent yields. KF-MFR proved to have unique termal and chemical resistance and can be reused for many consecutive runs without remarkable loss in catalytic activity. Copyright
- Rezaie, Ramin,Heidary, Mohammad,Soltani Rad, Mohammad Navid,Behrouz, Somayeh
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experimental part
p. 1221 - 1226
(2012/04/18)
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- Syntheses of potentially bioactive [1,2,4]oxadiazolo[5,4-d]benzothiazepines by 1,3-dipolar cycloaddition
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The chalcones, 2a-2l reacted with o-aminobenzenthiol to give a series of 1,5-benzothiazepines, 3a-3l. The [3+2] 1, 3-dipolar cycloaddition reactions of 3a-3l with ethyl chlorooximidoacetate in the presence of Et3N afforded the target compounds, 4a-4l possessing an additional 1,2,4-oxadiazole ring fused to the heptaatomic nucleus. The structures have been elucidated by spectral methods and X-ray crystallographic analysis.
- Wu, Xiao-Long,Liu, Fang-Ming,Shen, Song-Wei
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scheme or table
p. 1350 - 1355
(2011/01/05)
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- Synthesis and characterization of some new 2-amino-4-(4′-substituted) -6-(4″-substituted)diphenyl pyrimidines
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Synthesis and characterization of some novel 2-amino-4-(4′- substituted)-6-(4″-substituted)diphenyl pyrimidines has been carried out by the conversion of variably substituted acetophenones and benzaldehydes into corresponding chalcones followed by cyclization with guanidine hydrochloride in the presence of an oxidizing agent.
- Hasan, Aurangzeb,Khaleeq, Musfirah,Riaz, Uzma
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scheme or table
p. 5581 - 5587
(2012/08/07)
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- Hybrid α-bromoacryloylamido chalcones. Design, synthesis and biological evaluation
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Research into the anti-tumor properties of chalcones has received significant attention over the last few years Two novel large series of α-bromoacryloylamido chalcones 1a-m and 2a-k containing a pair of Michael acceptors in their structures, corresponding to the α-bromoacryloyl moiety and the α,β-unsaturated ketone system of the chalcone framework, were synthesized and evaluated for antiproliferative activity against five cancer cell lines. Such hybrid derivatives demonstrated significantly increased anti-tumor activity compared with the corresponding amino chalcones. The most promising lead molecules were 1k, 1m and 2j, which had the highest activity toward the five cell lines. Flow cytometry with K562 cells showed that the most active compounds resulted in a large proportion of the cells entering in the apoptotic sub-G0-G1 peak. Moreover, compound 1k induced apoptosis through the mitochondrial pathway and activated caspase-3.
- Romagnoli, Romeo,Baraldi, Pier Giovanni,Carrion, Maria Dora,Cruz-Lopez, Olga,Cara, Carlota Lopez,Balzarini, Jan,Hamel, Ernest,Canella, Alessandro,Fabbri, Enrica,Gambari, Roberto,Basso, Giuseppe,Viola, Giampietro
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supporting information; experimental part
p. 2022 - 2028
(2009/11/30)
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- Antifungal activity of chalcones: A mechanistic study using various yeast strains
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We reported the synthesis, antifungal evaluation and study on substituent effects of 21 chalcones. A lot of genetically defined strains belonging to different yeast genera and species, namely Saccharomyces cerevisiae, Hansenula polymorpha and Kluyveromyces lactis, were used as test organisms. Concerning the mode of the antifungal action of chalcones it was shown that DNA was probably not the main target for the chalcones. It was revealed that the yeast's intracellular glutathione and cysteine molecules play significant role as defence barrier against the chalcone action. It was also shown that chalcones may react with some proteins involved in cell separation.
- Lahtchev,Batovska,Parushev,Ubiyvovk,Sibirny
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p. 2220 - 2228
(2008/12/23)
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- Study on the substituents' effects of a series of synthetic chalcones against the yeast Candida albicans
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A large series of chalcones were synthesized and studied for activity against Candida albicans. The SAR analysis showed that the antifungal activity was highly dependent on the substitution pattern of the aryl rings and correlated to a large extent with the ability of compounds to interact with sulfhydryl groups. The most active were the hydroxylated chalcones as their activity related to the location of the phenolic group in the aryl ring B as follows: o-OH > p-OH ~ 3,4-di-OH > m-OH. These and other correlations obtained strongly contribute to the knowledge for design of anticandidal chalcones.
- Batovska,Parushev,Slavova,Bankova,Tsvetkova,Ninova,Najdenski
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- Multiple substituent effects on 13C chemical shifts in phenylstyryl ketones: Applicability of interactive free energy relationship
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13C chemical shifts for 23 mono- and di-substituted phenyl styryl ketones have been determined. The shieldings and deshieldings are compared with previous results for other aromatic derivatives. Correlations of the 13C chemical shifts of vinyl carbons with Hammett σ parameters has been determined to provide a consistent picture of electronic effects transmitted through the carbon framework of the compounds studied. Slopes obtained from such Hammett's plots are termed as ρ, and using these 'ρ' values applicability of interactive free energy relationship to chemical shift values has been tested. The cross- interaction constants qx and qy values for C-α are found to be -1.02 and -1.20 and for C-β are -1.46 and -1.19.
- Annapoorna,Prasad Rao,Sethuram
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p. 1341 - 1345
(2007/10/03)
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- Synthesis of 2-amino-4,5,7-triarylimidazo[1,5-b]pyridazines
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The reaction of 4-aryl-1,2-diaminoimidazoles with 1-aryl-2,3-dibromo-3-(4-nitrophenyl)propanones, 2-bromo-1-phenyl-3-(4-chlorophenyl)propenone, and 1,3-diarylpropynones yields 2-amino-4,5,7-triarylimidazo[1,5-b]-pyridazines. The structure of one of these products was determined by x-ray diffraction analysis. 1999 Kluwer Academic/Plenum Publishers.
- Kolos,Orlov,Paponov,Baumer
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p. 1189 - 1194
(2007/10/03)
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- Clemmensen reduction. XII The synthesis and acidolysis of some diaryl-substituted cyclopropane-1,2-diols. The possible involvement of a cyclopropyl cation
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The generation of a number of 1,2-diarylcyclopropane-1,2-diols is reported. Reaction of these in situ with acid gives, primarily, an α,β-unsaturated ketone in which the aryl substituent attached to the double bond is that which is best able to stabilize a benzylic cation. It is proposed that the reaction proceeds by O-protonation of the cyclopropane- 1,2-diol, followed by loss of water and opening of the resulting cyclopropyl cation and final deprotonation. Such initial O-protonation contrasts with the C-protonation normally observed in the acidolysis of cyclopropanols and other dialkyl- and alkylaryl-cyclopropane-1,2-diols.
- Davis, Brian R.,Hinds, Mark G.
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p. 309 - 319
(2007/10/03)
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- Electronic effects in the regioselectivity of nucleophilic attacks on cationic 1,3-diaryl-π-allylpalladium complexes
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Nucleophilic attacks on π-allylpalladium complexes derived from O2N-Ph-(CH-CH-CH)-Ph-X systems (X = 4-OMe and 4-Cl) occur preferentially at the allylic terminus remote from the electron-withdrawing group (NO2).
- Prat,Ribas,Moreno-Manas
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p. 1695 - 1706
(2007/10/02)
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- Interactive free energy relationships for non-additive multiple substituent effects in base catalysed condensation of benzaldehydes with acetophenones: A kinetic study
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The base-catalysed condensation of benzaldehydes with acetophenones is enhanced by electron-withdrawing substituents in both starting compounds.The magnitude of ρ-value obtained for various substituents in the benzaldehyde moiety decreases with the introduction of electron-withdrawing groups in the para position of acetophenone moiety.
- Sondu, S.,Sethuram, B,Rao, T. Navaneeth
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