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European Journal of Medicinal Chemistry

Ruo Wang, Xueyang Yin, Yaohuan Zhang, Weitao Yan
Twelve novel propylene-tethered ciprofloxacin-isatin hybrids 3a-f and 4a-f were designed, synthesized and characterized by MS, HRMS, 1 H NMR and 13 C NMR. All hybrids were evaluated for their in vitro antimicrobial activities against representative Gram-positive, Gram-negative and mycobacterial pathogens, cytotoxicity in VERO cell line as well as metabolic stability and in vivo pharmacokinetic (PK) properties. The preliminary results indicated that all mono-isatin-ciprofloxacin hybrids exhibited excellent antibacterial activities with MIC ranging from ≤0...
July 16, 2018: European Journal of Medicinal Chemistry
Yiming Xu, Lichuan Wu, Haroon Ur Rashid, Dewang Jing, Xiaole Liang, Haodong Wang, Xu Liu, Jun Jiang, Lisheng Wang, Peng Xie
Based on the mechanism of action, novel scaffolds as Topo I inhibitors bearing indole and sophoridinine were designed. Preliminary docking study revealed that some molecules among the designed series possessed promising Topo I inhibitor properties. Subsequently, thirty new compounds were synthesized and characterized by 1 H NMR, 13 C NMR, and Mass spectral analyses. The compounds were then screened for their antiproliferative and enzymatic inhibitory activities. The results affirmed the consistency between docking and activities and the rationality of the design strategy...
July 16, 2018: European Journal of Medicinal Chemistry
Martín Estrada Valencia, Clara Herrera-Arozamena, Lucía de Andrés, Concepción Pérez, José A Morales-García, Ana Pérez-Castillo, Eva Ramos, Alejandro Romero, Dolores Viña, Matilde Yáñez, Erik Laurini, Sabrina Pricl, María Isabel Rodríguez-Franco
In this work we describe neurogenic and neuroprotective donepezil-flavonoid hybrids (DFHs), exhibiting nanomolar affinities for the sigma-1 receptor (σ1 R) and inhibition of key enzymes in Alzheimer's disease (AD), such as acetylcholinesterase (AChE), 5-lipoxygenase (5-LOX), and monoamine oxidases (MAOs). In general, new compounds scavenge free radical species, are predicted to be brain-permeable, and protect neuronal cells against mitochondrial oxidative stress. N-(2-(1-Benzylpiperidin-4-yl)ethyl)-6,7-dimethoxy-4-oxo-4H-chromene-2-carboxamide (18) is highlighted due to its interesting biological profile in σ1 R, AChE, 5-LOX, MAO-A and MAO-B...
July 11, 2018: European Journal of Medicinal Chemistry
Jenny Desantis, Giulio Nannetti, Serena Massari, Maria Letizia Barreca, Giuseppe Manfroni, Violetta Cecchetti, Giorgio Palù, Laura Goracci, Arianna Loregian, Oriana Tabarrini
No abstract text is available yet for this article.
July 11, 2018: European Journal of Medicinal Chemistry
Michał Antoszczak, Alicja Urbaniak, Magdalena Delgado, Ewa Maj, Björn Borgström, Joanna Wietrzyk, Adam Huczyński, Youzhong Yuan, Timothy C Chambers, Daniel Strand
The polyether ionophore salinomycin has recently captured much interest due to its potent activity against multi-drug resistant cancer cells and cancer stem cells. Previous studies have shown that either acylation of the C20 position or esterification/amidation of the C1 carboxylate moiety is beneficial in terms of biological properties. In this paper, we present the first analogs combining such modifications. Evaluation of the anti-proliferative activity against a series of cancer cell lines showed that acylation of the C20 hydroxyl group improves the activity of salinomycin C1 amides but not of the corresponding C1 esters...
July 10, 2018: European Journal of Medicinal Chemistry
Jie Quan Wang, Xiaobin Wang, Yang Wang, Wen Jian Tang, Jing Bo Shi, Xin Hua Liu
In this study, twenty curcumin analogue hybrids as potential anticancer agents through regulation protein of TrxR were designed and synthesized. Results of anticancer activity showed that 5,7-dimethoxy-3-(3-(2-((1E, 4E)-3-oxo-5-(pyridin-2-yl)penta-1,4-dien-1- yl)phenoxy)propoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (compound 7d) could induce gastric cancer cells apoptosis by arresting cell cycle, break mitochondria function and inhibit TrxR activity. Meanwhile, western blot revealed that this compound could dramatically up expression of Bax/Bcl-2 ratio and high expression of TrxR oxidation...
July 10, 2018: European Journal of Medicinal Chemistry
Amina Qadir, Muhammad Riaz, Muhammad Saeed, Syed Shahzad-Ul-Hussan
Continuously increasing number of reports of Zika virus (ZIKV) infections and associated severe clinical manifestations, including autoimmune abnormalities and neurological disorders such as neonatal microcephaly and Guillain-Barré syndrome have created alarming situation in various countries. To date, no specific antiviral therapy or vaccine is available against ZIKV. This review provides a comprehensive insight into the potential therapeutic targets and describes viral epitopes of broadly neutralizing antibodies (bNAbs) in vaccine design perspective...
July 10, 2018: European Journal of Medicinal Chemistry
Tong-Hua Yang, Yun-Bao Ma, Chang-An Geng, De-Xiu Yan, Xiao-Yan Huang, Tian-Ze Li, Xue-Mei Zhang, Ji-Jun Chen
Depression is associated with high mortality and morbidity rates worldwide. By our random screening, it was first revealed that 23 magnolol derivatives were synthesized followed by in vitro and in vivo evaluation of their antidepressive potential. Compound 7c was found to be the most promising compound, with EC50 values of 396.5 and 383.0 μM agitating on MT1 and MT2 receptors, respectively. Additionally, we carried out in vivo experiments to confirm the efficacy and safety of compound 7c; the compound was found to be orally bioavailable and highly effective, leading to a significant reduction of immobility time in a mouse model of depression (forced swimming test and tail suspension test); the acting mechanism was explored by determining its effect on the levels of monoamine neurotransmitters and their metabolites in different mice brain regions; the acute toxicity study showed that the 50% lethal dose (LD50) of 7c was higher than 2000 mg/kg, p...
July 10, 2018: European Journal of Medicinal Chemistry
QingYou Mo, JunGang Deng, Yani Liu, GuiDong Huang, ZuoWen Li, Ping Yu, Yi Gou, Feng Yang
The ligand quantity, ligand type, and coordination geometry have important influences on the anticancer activity of metal-based complexes. On the basis of the structures of previously reported 1:1 Cu(II)/ligand complexes ([Cu(L1)Cl]·2H2 O 1a, [Cu(L2)Cl]·H2 O 2a, and [Cu(L2)NO3 ]·H2 O 3a), we subsequently designed, developed, and characterized a series of corresponding 1:1:1 Cu(II)/ligand/co-ligand complexes ([Cu(L1)(Py)Cl]·H2 O 1b, [Cu(L2)(Py)Cl] 2b, and [Cu(L2)(Py)NO3 ] 3b), where L1 = (E)-N'-(2-hydroxybenzylidene)acetohydrazide, L2 = (E)-N'-(2- hydroxybenzylidene)benzohydrazide, and Py = pyridine...
July 10, 2018: European Journal of Medicinal Chemistry
Simone Berardozzi, Flavia Bernardi, Paola Infante, Cinzia Ingallina, Sara Toscano, Elisa De Paolis, Romina Alfonsi, Miriam Caimano, Bruno Botta, Mattia Mori, Lucia Di Marcotullio, Francesca Ghirga
Aberrant activation of the Hedgehog (Hh) pathway is responsible for the onset and progression of several malignancies. Small molecules able to block the pathway at the upstream receptor Smoothened (Smo) or the downstream effector Gli1 have thus emerged recently as valuable anticancer agents. Here, we have designed, synthesized, and tested new Hh inhibitors taking advantage by the highly versatile and privileged isoflavone scaffold. The introduction of specific substitutions on the isoflavone's ring B allowed the identification of molecules targeting preferentially Smo or Gli1...
July 9, 2018: European Journal of Medicinal Chemistry
Dora C S Costa, Gabriella Silva de Almeida, Vitor Won-Held Rabelo, Lucio Mendes Cabral, Plínio Cunha Sathler, Paula Alvarez Abreu, Vitor Francisco Ferreira, Luiz Cláudio Rodrigues Pereira da Silva, Fernando de C da Silva
Naphthoquinones and 1,2,3-triazoles are structural pharmacophore that is known to impart several cancer cells. This work shows a synthetic methodology to obtain hybrid molecules involving naphthoquinone and triazol scaffold as multiple ligands. A simple and efficient synthetic route was used to prepare a series of sixteen compounds being eight 2-(1-aryl-1H-1,2,3-triazol-4-yl)-2,3-dihydronaphtho[1,2 b]furan-4,5-diones and eight 2-(1-aryl-1H-1,2,3-triazol-4-yl)-2,3-dihydronaphtho[2,3-b]furan-4,9-diones. These compounds were tested in MDA-MB231, Caco-2 and Calu-3 human cancer cells, and among them 7a was the most selective compound on Caco-2 cells, the most sensitized cell line in this study...
July 9, 2018: European Journal of Medicinal Chemistry
Chandra Bhushan Mishra, Shikha Kumari, Andrea Angeli, Silvia Bua, Martina Buonanno, Simona Maria Monti, Manisha Tiwari, Claudiu T Supuran
We report the design, synthesis and pharmacological assessment of novel benzenesulfonamide derivatives acting as effective carbonic anhydrase (CA, EC inhibitors. All the synthesized compounds were screened for their CA inhibitory action against four isoforms of human origin (h), i.e. hCA I, hCA II, hCA VII and hCA IX. In-vitro carbonic anhydrase inhibition studies have shown that first series, 4-(2-(4-(4-substitutedpiperazin-1-yl)benzylidene)hydrazinyl)benzenesulfonamides (4a- 4i) bestowed low nanomolar range to medium nanomolar range inhibitors against hCA II and hCA VII, effectively involved in epileptogenesis...
July 9, 2018: European Journal of Medicinal Chemistry
Islam Zaki, Mohammed K Abdelhameid, Ibrahim M El-Deen, Abdel Hady A Abdel Wahab, Abeer M Ashmawy, Khaled O Mohamed
Some triazinone derivatives are designed and synthesized as potential antitumor agents. Triazinone derivatives 4c, 5e and 7c show potent anticancer activity over MCF-7 breast cancer cells higher than podophyllotoxin (podo) by approximate 6-fold. DNA flow cytometry analysis for the compounds 3c, 4c, 5e, 6c and 7c show a potent inhibitory activity of cell proliferation and cell cycle arrest at G2 /M phase. Compounds 4c, 5e and 7c exhibit low to moderate β-tubulin polymerization inhibition percentage. Meanwhile, compound 6c displayed excellent β-tubulin percentage of polymerization inhibition equivalent to that exhibited by podo...
July 7, 2018: European Journal of Medicinal Chemistry
Pervaiz Ali Channar, Saira Afzal, Syeda Abida Ejaz, Aamer Saeed, Fayaz Ali Larik, Parvez Ali Mahesar, Joanna Lecka, Jean Sévigny, Mauricio F Erben, Jamshed Iqbal
In the present work we report the synthesis of new aryl pyrazole derivatives using 1,3-dicarbonyl motifs. The reaction was proceeded by the cyclization of pentane-2,4-dione (1a), 3-chloropentane-2,4-dione (1b) or ethyl 3-oxobutanoate (1c) with different aryl hydrazines. The products, which can be regarded as 1H-pyrazol-1-yl-one analogues (3a-f, 3g-o, 4a-c, 5a-b) and represent drug like molecules along with well-developed structure-activity relationships, were obtained in good to excellent yield. The structures of synthesized compounds were charcterized on the basis of FT-IR, 1 H NMR, 13 C NMR and mass spectroscopic data...
July 7, 2018: European Journal of Medicinal Chemistry
Cheng Shang See, Mayumi Kitagawa, Pei-Ju Liao, Kyung Hee Lee, Jasmine Wong, Sang Hyun Lee, Brian W Dymock
Selective targeting of cancer cells over normal cells is a key objective of targeted therapy. However few approaches achieve true mechanistic selectivity resulting in debilitating side effects and dose limitation. In this work we describe the discovery of A131 (4a), a new agent with an unprecedented dual mechanism of action targeting both mitosis and autophagy. Compound 4a was first identified in a phenotypic screen in which HeLa cells treated with 4a manifested mitotic arrest along with formation of multiple vesicles...
July 7, 2018: European Journal of Medicinal Chemistry
Shou-Jie Li, Xuan Zhang, Xiang-Hua Wang, Chang-Qi Zhao
Plant endophytes are microorganisms that live in healthy plant tissues in part or all of their life history without causing obvious symptoms of infection in the host plants. Endophytes, a new type of microbial resource that can produce a variety of biological constituents, have great values for research and broad prospects for development. This article reviewed the research and development progress of endophytic fungi with cytotoxic activity between 2014 and 2017, including endophytic fungi sources, microbial taxonomy, compound classification and cytotoxic activity...
July 7, 2018: European Journal of Medicinal Chemistry
Muhammad Kashif, Karla Fabiola Chacón-Vargas, Julio Cesar López-Cedillo, Benjamín Nogueda-Torres, Alma D Paz-González, Esther Ramírez-Moreno, Rosalia Agusti, Maria Laura Uhrig, Alicia Reyes-Arellano, Javier Peralta-Cruz, Muhammad Ashfaq, Gildardo Rivera
In the last two decades, trans-sialidase of Trypanosoma cruzi (TcTS) has been an important pharmacological target for developing new anti-Chagas agents. In a continuous effort to discover new potential TcTS inhibitors, 3-amino-3-arylpropionic acid derivatives (series A) and novel phthaloyl derivatives (series B, C and D) were synthesized and molecular docking, TcTS enzyme inhibition and determination of trypanocidal activity were carried out. From four series obtained, compound D-11 had the highest binding affinity value (-11...
July 7, 2018: European Journal of Medicinal Chemistry
Viktor Kolman, Filip Kalčic, Petr Jansa, Zdeněk Zídek, Zlatko Janeba
As a part of a broader structure-activity relationship study of substituted 2-aminopyrimidines, the influence of the C-5 substitution on inhibition of prostaglandin E2 (PGE2 ) production was studied. Thirty compounds were prepared starting from the corresponding 2-amino-4,6-dichloropyrimidines using Suzuki cross-coupling. It was shown previously that 2-amino-4,6-dichloropyrimidines with smaller C-5 substituent (hydrogen and methyl) were devoid of significant activity, while 5-butyl derivatives exhibited prominent potency...
July 6, 2018: European Journal of Medicinal Chemistry
Mohammed I El-Gamal, Byung-Jun Park, Chang-Hyun Oh
Twenty pyrazole-containing diarylureas and diarylamides were designed and synthesized. They were tested for in vitro antiproliferative activity over a 58-cancer cell line panel at the NCI, USA. The diarylurea derivatives 1b-e and 1g exerted the strongest antiproliferative activity. Among them, compound 1e possessing 3,5-bis(trifluoromethyl)phenyl terminal ring and 3`-methoxy-5`-chlorophenyl ring attached to the central pyrazole ring was the most potent. Its IC50 values were in sub-micromolar range against most of the tested cell lines...
July 6, 2018: European Journal of Medicinal Chemistry
Vera L M Silva, J Elguero, Artur M S Silva
The search of new antioxidants, as drugs candidates, is an active field of medicinal chemistry. The synthesis of compounds with antioxidant potential has increased in recent years and a high number of structurally diverse compounds have been published. This review aims to show the current state-of-the-art on the development of antioxidant compounds incorporating the pyrazole pharmacophore. It is a well-timed review driven by the increasing number of papers, on this issue, that have been published since the beginning of the 21st century (from 2000 to 2017)...
July 5, 2018: European Journal of Medicinal Chemistry
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