Description

Publisher details

Elsevier

Publications in this journal

• Synthesis and antimycobacterial activity of novel 1,3-dimethylisocyanurate derivatives.

  Authors: M M Shulaeva, S G Fattakhov, L F Saifina, R V Chestnova, R Sh Valijev, D N Mingaleev, A D Voloshina, V S Reznik

  European journal of medicinal chemistry.

  A series of novel 1,3-dimethylisocyanurates has been synthesized as potential inhibitors of β-ketoacyl synthase in mycobacteria. Most of the 25 compounds described and tested for their activityA series of novel 1,3-dimethylisocyanurates has been synthesized as potential inhibitors of β-ketoacyl synthase in mycobacteria. Most of the 25 compounds described and tested for their activity against M.tuberculosis have a bacteriostatic effect, comparable and even higher that of first-line antituberculosis drugs. These compounds are nontoxic, species-specific, exhibiting no activity against other bacterial species.

• Synthesis, in vitro and in silico screening of ethyl 2-(6-substituted benzo[d]thiazol-2-ylamino)-2-oxoacetates as protein-tyrosine phosphatase 1B inhibitors.

  Authors: Gabriel Navarrete-Vazquez, Marleth Ramírez-Martínez, Samuel Estrada-Soto, Carlos Nava-Zuazo, Paolo Paoli, Guido Camici, Jaime Escalante-García, José L Medina-Franco, Fabian López-Vallejo, Rolffy Ortiz-Andrade

  European journal of medicinal chemistry.

  The ethyl 2-(6-substituted benzo[d]thiazol-2-ylamino)-2-oxoacetate derivatives (OX 1-9) were prepared using a one-step reaction. The in vitro inhibitory activity of the compounds against proteinThe ethyl 2-(6-substituted benzo[d]thiazol-2-ylamino)-2-oxoacetate derivatives (OX 1-9) were prepared using a one-step reaction. The in vitro inhibitory activity of the compounds against protein tyrosine phosphatase 1B (PTP-1B) was evaluated. Compounds OX-(1, 6 and 7) were rapid reversible (mixed-type) inhibitors of PTP-1B with IC(50) values in the low micro-molar range. The most active compounds OX-(1, 6 and 7) were docked into the crystal structure of PTP-1B. Docking results indicate potential hydrogen bond interactions between the oxamate group in all compounds and the catalytic amino acid residues Arg221 and Ser216. The compounds were evaluated for their in vivo hypoglycemic activity, showing significant lowering of plasma glucose concentration in acute normoglycemic model and oral glucose tolerance test similarly at the effect exerted for hypoglycemic drug glibenclamide.

• Anticancer and radiosensitizing evaluation of some new pyranothiazole-Schiff bases bearing the biologically active sulfonamide moiety.

  Authors: Mostafa M Ghorab, Mohamed A Shaaban, Hanan M Refaat, Helmy I Heiba, Sara S Ibrahim

  European journal of medicinal chemistry.

  The present work reports the synthesis of some new Schiff bases, 5-(substituted benzylideneamino)-6-cyano-7H-7-(4-methoxyphenyl)-2-(4-sulphamoylphenylamino) pyrano[2,3-d]thiazole (5-15). The designThe present work reports the synthesis of some new Schiff bases, 5-(substituted benzylideneamino)-6-cyano-7H-7-(4-methoxyphenyl)-2-(4-sulphamoylphenylamino) pyrano[2,3-d]thiazole (5-15). The design of the structures of these compounds complies with the general pharmacophoric requirements for CA inhibiting anticancer drugs. The newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Most of the screened compounds showed interesting cytotoxic activities compared to doxorubicin as a reference drug. Compounds 4, 6-8 and 11 (IC(50): 27.51, 10.25, 9.55, 9.39 and 9.70 μM, respectively) exhibited higher cytotoxic activities than the reference drug doxorubicin (IC(50): 32.00 μM). Additionally, the previously mentioned compounds were evaluated again for their ability to enhance the cell killing effect of γ-radiation.

• Convenient synthesis of novel geiparvarin analogs with potential anti-cancer activity via click chemistry.

  Authors: Yikai Zhang, Zhiliang Lv, Hanyu Zhong, Dongping Geng, Mingfeng Zhang, Tao Zhang, Yongmei Li, Ke Li

  European journal of medicinal chemistry.

  Based on the advantages of natural products in new anti-cancer drug development, we synthesized a series of novel benzopyran-4-one derivatives and evaluated their in vitro anti-cancer activities. TheBased on the advantages of natural products in new anti-cancer drug development, we synthesized a series of novel benzopyran-4-one derivatives and evaluated their in vitro anti-cancer activities. The bioassays showed that the majority of the resultant compounds exerted anti-tumor effect against six human cancer cell lines to various extents, which supported the rationale of the design. Compound 5s exhibited highest potency of all the synthesized compounds.

• Alkylidene branched lupane derivatives: Synthesis and antitumor activity.

  Authors: René Csuk, Sebastian Stark, Christoph Nitsche, Alexander Barthel, Bianka Siewert

  European journal of medicinal chemistry.

  Several novel alkylidene branched lupane derivatives have been prepared. Many of these compounds showed a significant cytotoxicity. The most active compound, 2-methylene-betulonic acid, showed IC(50)Several novel alkylidene branched lupane derivatives have been prepared. Many of these compounds showed a significant cytotoxicity. The most active compound, 2-methylene-betulonic acid, showed IC(50) values between 0.2 and 0.6 μM for 15 different human cancer cell lines. Cytotoxicity can be improved by encapsulation in liposomes. These compounds act by triggering apoptotic cell death as shown by DNA-laddering experiments and acridine orange/ethidium bromide staining.

• Evaluation of synthetic acridones and 4-quinolinones as potent inhibitors of cathepsins L and V.

  Authors: Emerson F Marques, Mauro A Bueno, Patrícia D Duarte, Larissa R S P Silva, Ariani M Martinelli, Caio Y Dos Santos, Richele P Severino, Dieter Brömme, Paulo C Vieira, Arlene G Corrêa

  European journal of medicinal chemistry.

  Cathepsins, also known as lysosomal cysteine peptidases, are members of the papain-like peptidase family, involved in different physiological processes. In addition, cathepsins are implicated in manyCathepsins, also known as lysosomal cysteine peptidases, are members of the papain-like peptidase family, involved in different physiological processes. In addition, cathepsins are implicated in many pathological conditions. This report describes the synthesis and evaluation of a series of N-arylanthranilic acids, acridones, and 4-quinolinones as inhibitors of cathepsins V and L. The kinetics revealed that compounds of the classes of acridones are reversible competitive inhibitors of the target enzyme with affinities in the low micromolar range. They represent promising lead candidates for the discovery of novel competitive cathepsin inhibitors with enhanced selectivity and potency. On the other hand, 4-quinolinones were noncompetitive inhibitors and N-arylanthranilic acids were uncompetitive inhibitors.

• Chiral resolution, absolute configuration assignment and biological activity of racemic diarylpyrimidine CH(OH)-DAPY as potent nonnucleoside HIV-1 reverse transcriptase inhibitors.

  Authors: Shuang-Xi Gu, Zhi-Ming Li, Xiao-Dong Ma, Shi-Qiong Yang, Qiu-Qin He, Fen-Er Chen, Erik De Clercq, Jan Balzarini, Christophe Pannecouque

  European journal of medicinal chemistry.

  (+)-3a and (-)-3a were successfully separated from racemate (±)-3a by the chiral technique of supercritical fluid chromatography (SCF) with enantiomeric excess (ee%) >99% and purity >99%, and(+)-3a and (-)-3a were successfully separated from racemate (±)-3a by the chiral technique of supercritical fluid chromatography (SCF) with enantiomeric excess (ee%) >99% and purity >99%, and assigned for their absolute configuration as R and S, respectively, by the experimental electronic circular dichroism (ECD) spectrum and simulated ECD spectra calculated by time-dependent density functional theory (TDDFT) calculations. (+)-(R)-3a displayed excellent activity with an EC(50) of 5.3nM against wild-type HIV-1, which was 12-fold more potent than (-)-(S)-3a. However, (-)-(S)-3a showed higher potency than (+)-(R)-3a against the double HIV-1 RT mutant (K103N+Y181C) as well as HIV-2 strain ROD. The possible reason for the difference of (R)- and (S)-3a in anti-HIV-1 activity was interpreted by molecular docking.

• A solvent free, four-component synthesis and 1,3-dipolar cycloaddition of 4(H)-pyrans with nitrile oxides: Synthesis and discovery of antimycobacterial activity of enantiomerically pure 1,2,4-oxadiazoles.

  Authors: Abdulrahman I Almansour, Raju Suresh Kumar, Natarajan Arumugam, Dharmarajan Sriram

  European journal of medicinal chemistry.

  Four-component reactions of (R)-1-(1-phenylethyl)tetrahydro-4(1H)-pyridinone, aromatic aldehydes and malononitrile in a 1:2:1 molar ratio in the presence of solid sodium ethoxide under solvent freeFour-component reactions of (R)-1-(1-phenylethyl)tetrahydro-4(1H)-pyridinone, aromatic aldehydes and malononitrile in a 1:2:1 molar ratio in the presence of solid sodium ethoxide under solvent free conditions afforded an inseparable mixture of two diastereomeric 4(H)-pyrans in near quantitative yields. These compounds upon 1,3-dipolar cycloaddition with nitrile oxides furnished two enantiomerically pure 1,2,4-oxadiazoles in moderate yields, which were screened for in vitro activity against Mycobacterium tuberculosis H37Rv (MTB) and multi-drug resistant M.tuberculosis (MDR-TB). Among the compounds screened, compound 10h was found to be the most active in vitro with a MIC value of 0.07 and 0.14μM against MTB and MDR-TB respectively.

• Structure-activity relationships of saponin derivatives: A series of entry inhibitors for highly pathogenic H5N1 influenza virus.

  Authors: Ning Ding, Qing Chen, Wei Zhang, Sumei Ren, Ying Guo, Yingxia Li

  European journal of medicinal chemistry.

  The occurrence of highly pathogenic avian influenza virus H5N1 highlights the urgent need for new classes of antiviral drugs. Theoretically, each of steps in influenza viral life cycle can be aThe occurrence of highly pathogenic avian influenza virus H5N1 highlights the urgent need for new classes of antiviral drugs. Theoretically, each of steps in influenza viral life cycle can be a target of antiviral therapeutics. However, up to date, no licenced entry inhibitor drug is available for H5N1 or any other influenza viruses. Our strategy for developing new anti-influenza therapeutics is to target the interaction between HA and sialic acid which is influenza viral receptor presented on host cell surface. Here, based on our previously discovered small molecule inhibitor saponin 1, intensive SAR studies around the sugar chain and aglycone were conducted. The results showed that both the chacotriosyl residue and the chlorogenin moiety of active compound 1 are important for the antiviral activity, although several subtle modifications can be made on particular positions.

• Synthesis, hypoglycemic and hypolipidemic activities of novel thiazolidinedione derivatives containing thiazole/triazole/oxadiazole ring.

  Authors: A K Mohammed Iqbal, Ashraf Y Khan, Mallikarjun B Kalashetti, Ningaraddi S Belavagi, Young-Dae Gong, Imitiyaz Ahmed M Khazi

  European journal of medicinal chemistry.

  Novel thiazolidinedione derivatives were synthesized by incorporating pharmacologically significant heterocycles viz, substituted thiazole, triazole, and oxadiazole moieties linked to the centralNovel thiazolidinedione derivatives were synthesized by incorporating pharmacologically significant heterocycles viz, substituted thiazole, triazole, and oxadiazole moieties linked to the central phenyl ring via heteroatomlinkage with one/two carbon spacer as the structural analogs of Pioglitazone by employing multistep synthetic protocols. Structures of all the newly synthesized intermediates and target molecules were established by analytical and spectral data. These newly synthesized compounds were screened for their invivo hypoglycemic and hypolipidemic activities in male wistar rats. Some of the synthesized compounds demonstrated good activity.

• Synthesis and antiviral evaluation of C5-substituted-(1,3-diyne)-2'-deoxyuridines.

  Authors: Ozkan Sari, Vincent Roy, Jan Balzarini, Robert Snoeck, Graciela Andrei, Luigi A Agrofoglio

  European journal of medicinal chemistry.

  Starting from acetylated 5-ethynyl-2'-deoxyuridine (3), 14 hitherto unknown C5-substituted-(1,3-diyne)-2'-deoxyuridines (with cyclopropyl, hydroxymethyl, methylcyclopentane, p-(substituted)phenyl andStarting from acetylated 5-ethynyl-2'-deoxyuridine (3), 14 hitherto unknown C5-substituted-(1,3-diyne)-2'-deoxyuridines (with cyclopropyl, hydroxymethyl, methylcyclopentane, p-(substituted)phenyl and disubstituted-phenyl substituents) have been synthesized via a nickel-copper catalyzed C-H activation between two terminal alkynes, in yields ranging from 19% to 67%. Their antiviral activities were measured against a large number of DNA and RNA viruses including herpes simplex virus type 1 and type 2, varicella-zoster virus, human cytomegalovirus and vaccinia virus. The 5-[4-(4-trifluoromethoxyphenyl)buta-1,3-diynyl]-2'-deoxyuridine (26) is the most potent inhibitor of this series against VZV with an EC(50) of ∼1 μM and a CC(50) of 55 μM. Their cytostatic activities were determined against murine leukemia cells, human T-lymphocyte cells and cervix carcinoma cells. Compounds were also evaluated on a wide panel of RNA viruses, including influenza virus A (H1N1 and H3N2) and B in MDCK cell cultures, parainfluenza-3 virus, reovirus-1, Sindbis virus and Punta Toro virus in Vero cell cultures and vesicular stomatitis, coxsackie B4 and respiratory syncytial virus in HeLa cell cultures and against human immunodeficiency virus type 1 and 2 in CEM cell cultures, with no specific antiviral effect. This class of compounds could be of further interest for lead optimization as anti-infectious (i.e. herpetic) agents.

• Microwave assisted synthesis of spirocyclic pyrrolidines -σ(1) receptor ligands with modified benzene-N-distance.

  Authors: Annemarie Jasper, Dirk Schepmann, Kirstin Lehmkuhl, Jose Miguel Vela, Helmut Buschmann, Jörg Holenz, Bernhard Wünsch

  European journal of medicinal chemistry.

  Two series of σ(1) ligands with a spiro[[2]benzopyran-1,3'-pyrrolidine] (3) and a spiro[[2]benzofuran-1,3'-pyrrolidine] (4) framework were synthesized and pharmacologically evaluated. SeveralTwo series of σ(1) ligands with a spiro[[2]benzopyran-1,3'-pyrrolidine] (3) and a spiro[[2]benzofuran-1,3'-pyrrolidine] (4) framework were synthesized and pharmacologically evaluated. Several reaction steps were considerably improved by microwave irradiation. The σ(1) affinity of the spirocyclic ligands correlates nicely with the benzene-N-distance, i.e. 2 < 3 < 4 < 1. The σ(1) affinity of both compound classes could be increased with large N-substituents (e.g. 2-phenylethyl, octyl). Nevertheless the benzyl derivative 4a represents the most promising σ(1) ligand (K(i) = 25 nM) due to its high selectivity against the σ(2) subtype (>40-fold), the NMDA receptor and 5-HT(6) and 5-HT(7) receptors. Moreover, 4a did not inhibit the hERG channel in the heart.

• Synthesis and in vitro characterization of trans- and cis-[(18)F]-4-methylbenzyl 4-[(pyrimidin-2-ylamino)methyl]-3-fluoropiperidine-1-carboxylates as new potential PET radiotracer candidates for the NR2B subtype N-methyl-d-aspartate receptor.

  Authors: Radouane Koudih, Gwénaëlle Gilbert, Martine Dhilly, Ahmed Abbas, Louisa Barré, Danièle Debruyne, Franck Sobrio

  European journal of medicinal chemistry.

  Diastereoisomeric compounds [(18)F]cis- and [(18)F]trans-4-methylbenzyl 4-[(pyrimidin-2-ylamino)methyl]-3-fluoro-piperidine-1-carboxylates were successfully synthesized as new subtype-selective PETDiastereoisomeric compounds [(18)F]cis- and [(18)F]trans-4-methylbenzyl 4-[(pyrimidin-2-ylamino)methyl]-3-fluoro-piperidine-1-carboxylates were successfully synthesized as new subtype-selective PET radiotracers for imaging the NR2B subunit containing NMDA receptors. Rat brain section autoradiographies demonstrated a high specific binding in NR2B/NMDA receptor rich regions for both radioligands. The measured logD(7.4) values as well as B(max)/K(d) ratios indicated that both radiotracers possess the adequate properties required for PET radiotracers.

• Design, synthesis and antiviral activity of novel quinazolinones.

  Authors: Ziwen Wang, Mingxiao Wang, Xue Yao, Yue Li, Juan Tan, Lizhong Wang, Wentao Qiao, Yunqi Geng, Yuxiu Liu, Qingmin Wang

  European journal of medicinal chemistry.

  HIV-1 integrase (IN) is a validated therapeutic target for antiviral drug design. However, the emergence of viral strains resistant to clinically studied IN inhibitors demands the discovery of novelHIV-1 integrase (IN) is a validated therapeutic target for antiviral drug design. However, the emergence of viral strains resistant to clinically studied IN inhibitors demands the discovery of novel inhibitors that are structurally as well as mechanistically different. Herein, a series of quinazolinones were designed and synthesized as novel HIV-1 inhibitors. The new synthetic route provides a practical method for the preparation of 5-hydroxy quinazolinones. Primary bioassay results indicated that most of the quinazolinones possess anti-HIV activity, especially for compound 11b with 77.5% inhibition rate at 10μM emerged as a new active lead. Most of the synthesized compounds were also found to exhibit good anti-TMV activity, of which compound 9a showed similar in vivo anti-TMV activity to commercial plant virucide Ribavirin. This work provides a new and efficient approach to evolve novel multi-functional antiviral agents by rational integration and optimization of previously reported antiviral agents.

• Synthesis, characterization, antimicrobial activities and QSAR studies of some 10a-phenylbenzo[b]indeno[1,2-e][1,4]thiazin-11(10aH)-ones.

  Authors: Satbir Mor, Preeti Pahal, Balasubramanian Narasimhan

  European journal of medicinal chemistry.

  A series of 10a-phenylbenzo[b]indeno[1,2-e][1,4]thiazin-11(10aH)-ones (3) has been synthesized and tested for their antimicrobial activity. The antimicrobial evaluation data indicated that compounds,A series of 10a-phenylbenzo[b]indeno[1,2-e][1,4]thiazin-11(10aH)-ones (3) has been synthesized and tested for their antimicrobial activity. The antimicrobial evaluation data indicated that compounds, 3b, 3d, 3k and 3m exhibited very promising antibacterial activity and the compounds 3b and 3k exhibited notable activity, almost comparable to penicillin for Staphylococcus aureus and Bacillus subtilis respectively. The derivatives 3g and 3l exhibited high antifungal activity. Moreover, antibacterial activities were more prolific than antifungal activity. The QSAR studies indicated the importance of topological parameters, Kiers second order molecular index (κα(2)) and molecular connectivity index (χ) in describing the antibacterial activity and electronic parameters, the energy of highest occupied molecular orbital (HOMO) and the dipole moment (μ) in describing the antifungal activity.

• Design, synthesis and structure-activity relationships of new triazole derivatives containing N-substituted phenoxypropylamino side chains.

  Authors: Shengzheng Wang, Gang Jin, Wenya Wang, Lingjian Zhu, Yongqiang Zhang, Guoqiang Dong, Yang Liu, Chunlin Zhuang, Zhenyuan Miao, Jianzhong Yao, Wannian Zhang, Chunquan Sheng

  European journal of medicinal chemistry.

  The incidence of invasive fungal infections and resistance to antifungal agents is increasing dramatically. It is highly desirable to develop novel azoles with improved biological profiles. TheThe incidence of invasive fungal infections and resistance to antifungal agents is increasing dramatically. It is highly desirable to develop novel azoles with improved biological profiles. The structure-activity relationship (SAR) of the N-substitutions was investigated in this study. In vitro antifungal activities revealed that sterically large groups were not favored for the N-substitutions. The removal of the N-substitutions had little effect on the antifungal activity. Two compounds with free amine group (i.e.9a and 10a) showed excellent activity with broad antifungal spectrum. The SAR results were supported by molecular docking and the N-substitutions were found to be important for the conformation of the side chains. The SAR and binding mode of the azoles are useful for further lead optimization.

• β-Lapachone analogs with enhanced antiproliferative activity.

  Authors: Carla Ríos-Luci, Evelyn L Bonifazi, Leticia G León, Juan C Montero, Gerardo Burton, Atanasio Pandiella, Rosana I Misico, José M Padrón

  European journal of medicinal chemistry.

  In this study, we describe the synthesis of a series of α- and β-lapachone containing hydroxyl or methoxyl groups on the benzene ring, by means of the selective acid promoted cyclization of theIn this study, we describe the synthesis of a series of α- and β-lapachone containing hydroxyl or methoxyl groups on the benzene ring, by means of the selective acid promoted cyclization of the appropriate lapachol analog. The evaluation of the antiproliferative activity in human solid tumor cell lines provided 7-hydroxy-β-lapachone as lead with enhanced activity over the parent drug β-lapachone. Cell cycle studies, protein expression experiments, and reactive oxygen species analysis revealed that, similarly to β-lapachone, ROS formation and DNA damage are critical factors in the cellular toxicity of 7-hydroxy-β-lapachone.

• Synthesis and fungicidal activity of novel pimprinine analogues.

  Authors: Ming-Zhi Zhang, Qiong Chen, Nick Mulholland, David Beattie, Dianne Irwin, Yu-Cheng Gu, Guang-Fu Yang, John Clough

  European journal of medicinal chemistry.

  A simple and efficient synthetic protocol for 5-(3-indolyl)-oxazoles has been developed and further used to synthesize a series of novel analogues of natural product pimprinine. All new compoundsA simple and efficient synthetic protocol for 5-(3-indolyl)-oxazoles has been developed and further used to synthesize a series of novel analogues of natural product pimprinine. All new compounds were identified by (1)H NMR, high resolution mass spectrometry, and the structures of 10 and 18o were further confirmed by X-ray crystallographic diffraction analysis. Bioassay conducted at Syngenta showed that several of the synthesized compounds exhibited fungicidal activity. Compounds 10, 17, 18h, 18o, 19h, 19i and 19l all showed effective control of three out of the seven tested phytopathogenic fungi at the highest rate screened. Compounds 17 and 19h in particular showed activity against the four pathogens screened in artificial media; Pythium dissimile, Alternaria solani, Botryotinia fuckeliana and Gibberella zeae.

• Synthesis and evaluation of curcumin-related compounds for anticancer activity.

  Authors: Xingchuan Wei, Zhi-Yun Du, Xi Zheng, Xiao-Xing Cui, Allan H Conney, Kun Zhang

  European journal of medicinal chemistry.

  Sixty-one curcumin-related compounds were synthesized and evaluated for their anticancer activity toward cultured prostate cancer PC-3 cells, pancreas cancer Panc-1 cells and colon cancer HT-29Sixty-one curcumin-related compounds were synthesized and evaluated for their anticancer activity toward cultured prostate cancer PC-3 cells, pancreas cancer Panc-1 cells and colon cancer HT-29 cells. Inhibitory effects of these compounds on the growth of PC-3, Panc-1 and HT-29 cells were determined by the MTT assay. Compounds E10, F10, FN1 and FN2 exhibited exceptionally potent inhibitory effects on the growth of cultured PC-3, Panc-1 and HT-29 cells. The IC(50) for these compounds was lower than 1 μM in all three cell lines. E10 was 72-, 46- and 117-fold more active than curcumin for inhibiting the growth of PC-3, Panc-1 and HT-29 cells, respectively. F10 was 69-, 34- and 72-fold more active than curcumin for inhibiting the growth of PC-3, Panc-1 and HT-29 cells, respectively. FN1 and FN2 had about the same inhibitory effect as E10 and F10 toward Panc-1 cells but were less active than E10 and F10 toward PC-3 and HT-29 cells. The active compounds were potent stimulators of apoptosis. The present study indicates that E10, F10, FN1 and FN2 may have useful anticancer activity.

• 2-Anilino-4-(benzimidazol-2-yl)pyrimidines - A multikinase inhibitor scaffold with antiproliferative activity toward cancer cell lines.

  Authors: Renate Determann, Jan Dreher, Knut Baumann, Lutz Preu, Peter G Jones, Frank Totzke, Christoph Schächtele, Michael H G Kubbutat, Conrad Kunick

  European journal of medicinal chemistry.

  2-Anilino-4-(benzimidazol-2-yl)-pyrimidines, synthesized by reaction of a readily available benzimidazole-substituted enaminone with suitable arylguanidines, were shown to inhibit four cancer-related2-Anilino-4-(benzimidazol-2-yl)-pyrimidines, synthesized by reaction of a readily available benzimidazole-substituted enaminone with suitable arylguanidines, were shown to inhibit four cancer-related protein kinases (Aurora B, PLK1, FAK, and VEGF-R2). The most potent derivative exhibited antiproliferative activity for several cancer cell lines of the NCI in vitro cell line panel in submicromolar concentrations. Both the anilinopyrimidine structure and the substitution pattern at the aniline ring appear to be important for the protein kinase inhibitory activity.

• Synthesis, anti-Candida activity, and cytotoxicity of new (4-(4-iodophenyl)thiazol-2-yl)hydrazine derivatives.

  Authors: Daniela Secci, Bruna Bizzarri, Adriana Bolasco, Simone Carradori, Melissa D'Ascenzio, Daniela Rivanera, Emanuela Mari, Lucia Polletta, Alessandra Zicari

  European journal of medicinal chemistry.

  Novel (4-(4-iodophenyl)-thiazol-2-yl)hydrazine derivatives were assayed for their in vitro anti-Candida activity, compared to topical and systemic antifungal drugs, against twenty-seven clinicalNovel (4-(4-iodophenyl)-thiazol-2-yl)hydrazine derivatives were assayed for their in vitro anti-Candida activity, compared to topical and systemic antifungal drugs, against twenty-seven clinical isolates. The presence of aliphatic chains or specific heteroaromatic rings on hydrazone moiety at position C2 and a 4-iodophenyl at C4 of the thiazole ring gave a promising inhibitory activity especially against Candidaalbicans and Candidakrusei. The most active compounds have been also evaluated for their cytotoxicity and in association with clotrimazole for anti-Candida activity.

• Synthesis of new 2-galactosylthiazolidine-4-carboxylic acid amides. Antitumor evaluation against melanoma and breast cancer cells.

  Authors: Arménio C Serra, António M d'A Rocha Gonsalves, Mafalda Laranjo, Ana M Abrantes, Ana C Gonçalves, Ana B Sarmento-Ribeiro, M Filomena Botelho

  European journal of medicinal chemistry.

  A set of 2-galactosylthiazolidine-4-carboxylic acid amides was synthesized with different length for the carbon chain amide moiety. The cytotoxicity of the molecules was evaluated against A375A set of 2-galactosylthiazolidine-4-carboxylic acid amides was synthesized with different length for the carbon chain amide moiety. The cytotoxicity of the molecules was evaluated against A375 melanoma and MCF7 breast cancer cell lines. For the derivatives tested, the one that contains a C(16) amide carbon chain is the most active with an IC(50) of 17.0 μM for A375 and 5.8 μM for MCF7. This compound also shows cytotoxicity in the triple negative cancer cell line HCC1806. The selectivity of the compounds was assessed by comparing the cytotoxicity in cancer cell line versus in a fibroblast cell line. Flow cytometry studies show the activation of apoptotic pathways and also DNA damages with blockage of the cell cycle in the S-phase and appearance of peaks in G0/G1-phase.

• Appraisal of GABA and PABA as linker: Design and synthesis of novel benzamide based histone deacetylase inhibitors.

  Authors: Harish Rajak, Pramod Kumar, Poonam Parmar, Bhupendra Singh Thakur, Ravichandran Veerasamy, Prabodh Chander Sharma, Ajay Kumar Sharma, Arun Kumar Gupta, Jawahar Singh Dangi

  European journal of medicinal chemistry.

  Histone deacetylase inhibitors have been actively explored as a new generation of chemotherapeutics for cancers, generally known as epigenetic therapeutics. Two novel series ofHistone deacetylase inhibitors have been actively explored as a new generation of chemotherapeutics for cancers, generally known as epigenetic therapeutics. Two novel series of N-(2-amino-phenyl)-4-{[(2/3/4-substituted-phenylcarbamoyl)-methyl]-amino}-butyramide and N-(2-amino-phenyl)-4-{[(2/3/4-substituted-phenylcarbamoyl)-methyl]-amino}benzamide were designed and synthesized as novel histone deacetylase inhibitors. The anticancer potential of the compounds were determined in-vitro using MTT assay against HCT-116 and U251 (glioma) cell lines and histone deacetylase inhibitory assay. The synthesized compounds were investigated for anti-tumor activity against Ehrlich ascites carcinoma (EAC) cells in Swiss albino mice. The efforts were also made to ascertain structure-activity relationships among test compounds. The results of the present studying represents appraisal of γ-aminobutyric acid (GABA) and para-aminobenzoic acid (PABA) as linker moiety for development of newer benzamide based histone deacetylase inhibitor.

• New quinazolinone-pyrimidine hybrids: Synthesis, anti-inflammatory, and ulcerogenicity studies.

  Authors: Safinaz E Abbas, Fadi M Awadallah, Nashwa A Ibrahin, Eman G Said, Gihan M Kamel

  European journal of medicinal chemistry.

  Two groups of hybrid compounds: the quinazolinone-dihydropyrimidines and quinazolinone-pyrimidines, were synthesized. The starting derivative 3 was reacted with chloroacetyl chloride to giveTwo groups of hybrid compounds: the quinazolinone-dihydropyrimidines and quinazolinone-pyrimidines, were synthesized. The starting derivative 3 was reacted with chloroacetyl chloride to give intermediate 5 which was condensed with the 2-mercaptopyrimidines 4a-c affording compounds 6a-c. These latter compounds underwent hydrolysis and N-alkylation reactions to give the dihydropyrimidine derivatives 7a-c and 8a-f, respectively. The chloro derivatives 9a-c subsequently reacted with various anilines furnishing compounds 10a-i. The anti-inflammatory activity of the synthesized compounds were evaluated using the carrageenan-induced rat paw oedema model and ulcer indices for the most active compounds were calculated. Five compounds were found more active and less ulcerogenic than diclofenac particularly compound 10g (IC(50)=116.73μmol/kg; ulcer index=11.38). Compound 10g was also 2-fold more selective inhibitor of COX-2 than COX-1.

• Discovery, design and synthesis of Y-shaped peroxisome proliferator-activated receptor δ agonists as potent anti-obesity agents in vivo.

  Authors: Jungyeob Ham, Hoosang Hwang, Euno Kim, Jeong-Ah Kim, Sung Jin Cho, Jaeyoung Ko, Woojin Lee, Jaehwan Lee, Harish Holla, Joydeep Banerjee [......] Jungae Tak, Dongyup Hahn, Taekyung Oh, Dong Hwan Won, Tae Gu Lee, Jihye Choi, Mi Sun Park, Chaok Seok, Jungwook Chin, Heonjoong Kang

  European journal of medicinal chemistry.

  We have discovered and demonstrated the in vitro and in vivo PPARδ-selective activity of novel Y-shaped agonists. These compounds activated hPPARδ with EC(50) values between 1 and 523 nM.We have discovered and demonstrated the in vitro and in vivo PPARδ-selective activity of novel Y-shaped agonists. These compounds activated hPPARδ with EC(50) values between 1 and 523 nM. Surprisingly, compounds 10a, 11d, 11e and 11f were the most potent and most selective hPPARδ agonists with 10(4)-fold selectivity over the other two subtypes, namely, hPPARα and hPPARγ. The PPARδ ligands 10a, 11e and 11f showed good bioavailability and in vivo efficacy.

Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.