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Future Medicinal Chemistry

Carmela Saturnino, Ines Barone, Domenico Iacopetta, Annaluisa Mariconda, Maria Stefania Sinicropi, Camillo Rosano, Antonella Campana, Stefania Catalano, Pasquale Longo, Sebastiano Andò
AIM: Metal carbenic complexes have received considerable attention in both the catalysis and biological fields for their potential applications in cancer and antimicrobial therapies. RESULTS: A small series of new silver and gold N-heterocyclic carbene complexes has been designed and synthesized. Among the tested complexes, one compound was particularly active in inhibiting anchorage-dependent and -independent breast cancer proliferation, and inducing cell apoptosis via a mitochondria-related process...
November 22, 2016: Future Medicinal Chemistry
Luca Gentilucci, Pierluigi Tosi, Adriano Bauer, Rossella De Marco
The ability to improve nature's capacity by introducing modification of biological interest in proteins and peptides (P&P) is one of the modern challenges in synthetic chemistry. Due to the unfavorable pharmacokinetic properties, many native P&P are of little use as therapeutic agents. Today, few methods for the preparation of modified proteins are available. Initially introduced to realize the ligation between two standard peptidic sequences, and hence to afford native proteins, the modern chemical methodologies, in other words native chemical ligation, expressed ligation, Staudinger ligation, auxiliary mediated ligation, aldehyde capture, etc...
November 22, 2016: Future Medicinal Chemistry
Mickaël Marloye, Gilles Berger, Michel Gelbcke, François Dufrasne
Metal complexes have been the subject of numerous investigations in oncology but, despite the plethora of newly synthesized compounds, their precise mechanisms of action remain generally unknown or, for the best, incompletely determined. The continuous development of efficient and sensitive techniques in analytical chemistry and molecular biology gives scientists new tools to gather information on how metal complexes can be effective toward cancer. This review focuses on recent findings about the anticancer mechanism of action of metal complexes and how the ligands can be used to tune their pharmacological and physicochemical properties...
November 22, 2016: Future Medicinal Chemistry
Andreas Koeberle
No abstract text is available yet for this article.
November 15, 2016: Future Medicinal Chemistry
Mohammad Ashrafuddin Khan, Mohammed I El-Gamal, Hamadeh Tarazi, Hong Seok Choi, Chang-Hyun Oh
BACKGROUND: Inhibition of V600E-B-RAF kinase represents a potential avenue for melanoma treatment. Herein, a series of 1,3,4-triarylpyrazoles possessing amide linker were designed, synthesized and evaluated for RAF kinase inhibition. RESULTS: Compounds 1d and 1f were more potent than sorafenib against A375 cell line, and their selectivity indexes toward A375 than HS27 fibroblasts were 25.43 and 45.83, respectively. Compound 1f was more potent against the melanoma cell lines with B-RAF V600E mutation than melanoma cells with NRAS mutation and normal skin epithelial cells...
November 15, 2016: Future Medicinal Chemistry
Robert A Copeland
No abstract text is available yet for this article.
November 15, 2016: Future Medicinal Chemistry
Bianca C Bernardo, Kate L Weeks, Natalie L Patterson, Julie R McMullen
Heat shock proteins are a family of proteins that are produced by cells in response to exposure to stressful conditions. The best studied heat shock protein is HSP70, which is known to act as a molecular chaperone to maintain cellular homeostasis and inhibit protein aggregation in response to stress. While early animal studies suggested that increasing HSP70 in the heart (using a transgenic, gene transfer or pharmacological approach) provided cardiac protection against acute cardiac stress, recent studies have found no benefit of increasing HSP70 in mouse models of chronic cardiac stress...
November 15, 2016: Future Medicinal Chemistry
Elżbieta Kamysz, Maciej Sałaga, Małgorzata Sobocińska, Artur Giełdoń, Jakub Fichna
AIM: The pharmacotherapy of inflammatory bowel disease is difficult and currently available treatments bring mostly poor and unsatisfactory results. RESULTS: The purpose of this work was the synthesis of opiorphin, sialorphin, spinorphin and a series of their analogs and the in vitro characterization of their effect on degradation of enkephalin by neutral endopeptidase and aminopeptidase N. Consequently, we investigated in vivo the anti-inflammatory effect of the most active inhibitors selected in the in vitro studies (Pal-KKQRFSR & Pal-KKQHNPR)...
November 15, 2016: Future Medicinal Chemistry
Azucena Marset, Paloma Begines, Óscar López, Inés Maya, Natalia García-Aranda, Simó Schwartz, Ibane Abasolo, José G Fernández-Bolaños
AIM: Numerous chronic diseases exhibit multifactorial etiologies, so focusing on a single therapeutic target is usually an inadequate treatment; instead, multi-target drugs are preferred. Herein, a panel of phenolic thioureas and selenoureas were designed as new prototypes against multifactorial diseases concerning antioxidation and cytotoxicity, as a pro-oxidant environment is usually found in such diseases. RESULTS: Selenoureas were excellent antiradical agents and biomimetic catalysts of glutathione peroxidase for the scavenging of H2O2...
November 15, 2016: Future Medicinal Chemistry
M Amélia Santos, Karam Chand, Sílvia Chaves
Alzheimer's disease (AD) is a serious progressive neurological disorder, characterized by impaired cognition and profound irreversible memory loss. The multifactorial nature of AD and the absence of a cure so far have stimulated medicinal chemists worldwide to follow multitarget drug-design strategies based on repositioning approved drugs. This review describes a summary of recently published works focused on tailoring new derivatives of US FDA-approved acetylcholinesterase inhibitors, in addition to huperzine (a drug approved in China), either by hybridization with other pharmacophore elements (to hit more AD targets), or by combination of two FDA-approved drugs...
October 24, 2016: Future Medicinal Chemistry
Pedro Alves Bezerra Morais, Renata Dalmaschio Daltoé, Heberth de Paula
The discovery of the importance of kinase activity and its relationship to the emergence and proliferation of cancer cells, due to changes in normal physiology, opened a remarkable pathway for the treatment of chronic myelogenous leukemia through intense search of drug candidates. Six Abl kinase inhibitors have received the US FDA approval as chronic myelogenous leukemia treatment, and continuous efforts in obtaining new, more effective and selective molecules are being carried out. Herein we discuss the mechanisms of Abl inhibition, structural features and ligand/protein interactions that are important for the design of new Abl kinase inhibitors...
October 24, 2016: Future Medicinal Chemistry
Tinghan Li, Tianwei Weng, Minzan Zuo, Zhihui Wei, Ming Chen, Zhiyu Li
Deregulation of the cell cycle is a common feature in human cancer. The inhibition of cyclin-dependent kinases (CDKs), which play a crucial role in control of the cell cycle, has always been one of the most promising areas in cancer chemotherapy. This review first summarizes the biology of CDKs and then focuses on the recent advances in both broad-range and selective CDK inhibitors during the last 5 years. The design rationale, structural optimization and structure-activity relationships analysis of these small molecules have been discussed in detail and the key interactions with the amino-acid residues of the most important compounds are highlighted...
October 24, 2016: Future Medicinal Chemistry
Shaghayegh Fathi, Adegboyega K Oyelere
Liposomes are biodegradable and biocompatible self-forming spherical lipid bilayer vesicles. They can encapsulate and deliver one or more hydrophobic and hydrophilic therapeutic agents with poor therapeutic indices to tumor sites. Properties such as lipid bilayer fluidity, charge, size and surface hydration can be modified to extend liposome circulation time in the bloodstream and enhance efficacy. The focus of this review is on ligand-conjugated liposomes and their potential application in tumor-targeted delivery...
October 24, 2016: Future Medicinal Chemistry
Robert Cooke, Miles Congreve
No abstract text is available yet for this article.
October 14, 2016: Future Medicinal Chemistry
Juliane K Mueller, Cathrin Rohleder, F Markus Leweke
No abstract text is available yet for this article.
October 14, 2016: Future Medicinal Chemistry
Giulia Caron, Giuseppe Ermondi
No abstract text is available yet for this article.
October 14, 2016: Future Medicinal Chemistry
Simona Panella, Maria Elena Marcocci, Ignacio Celestino, Sergio Valente, Clemens Zwergel, Domenica Donatella Li Puma, Lucia Nencioni, Antonello Mai, Anna Teresa Palamara, Giovanna Simonetti
AIM: Histone deacetylases (HDACs) regulate the life-cycle of several viruses. We investigated the ability of different HDAC-inhibitors, to interfere with influenza virus A/Puerto Rico/8/34/H1N1 (PR8 virus) replication in Madin-Darby canine kidney and NCI cells. RESULTS: 3-(5-(3-Fluorophenyl)-3-oxoprop-1-en-1-yl)-1-methyl-1H-pyrrol-2-yl)-N-hydroxyacrylamide (MC1568) inhibited HDAC6/8 activity and PR8 virus replication, with decreased expression of viral proteins and their mRNAs...
October 14, 2016: Future Medicinal Chemistry
Jeffrey J Coleman, Tomomi Komura, Julia Munro, Michael P Wu, Rakhee R Busanelli, Angela N Koehler, Méryl Thomas, Florence F Wagner, Edward B Holson, Eleftherios Mylonakis
AIM: Caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE), the major constituent of propolis, is able to increase the survival of the nematode Caenorhabditis elegans after infection with the fungal pathogen Candida albicans. RESULTS: CAPE increases the expression of several antimicrobial proteins involved in the immune response to C. albicans. Structural derivatives of CAPE were synthesized to identify structure-activity relationships and decrease metabolic liability, ultimately leading to a compound that has similar efficacy, but increased in vivo stability...
October 14, 2016: Future Medicinal Chemistry
Yaxia Yuan, Xiaoqin Huang, Jun Zhu, Chang-Guo Zhan
This is a brief review of computational modeling studies on the detailed structures and mechanism of human dopamine transporter (hDAT), as well as its interaction with HIV-1 transactivator of transcription (Tat). Extensive molecular modeling, docking and dynamics simulations have resulted in reasonable structural models of hDAT in three typical conformational states, its dopamine uptake mechanism and its interaction with Tat. The obtained hDAT models in different conformational states and their complexes with dopamine and Tat have provided novel structural and mechanistic insights concerning how hDAT uptakes dopamine and how Tat affects the dopamine uptake by hDAT...
October 14, 2016: Future Medicinal Chemistry
Xin-Mei Peng, Li-Ping Peng, Shuo Li, Avula Srinivasa Rao, Kannekanti Vijaya Kumar, Shao-Lin Zhang, Kin Yip Tam, Cheng-He Zhou
AIM: Due to bacterial drug resistance, a new series of quinazolinone azolyl ethanols were synthesized and evaluated. RESULTS: In vitro antibacterial assay showed that triazolyl ethanol quinazolinone 3a was the most active compound, especially against methicillin-resistant Staphylococcus aureus (MRSA) with minimal inhibitory concentration value of 8 µg/ml, which was superior to chloromycin and comparable to norfloxacin. Molecular docking study displayed that compound 3a could interact with MRSA DNA by the formation of hydrogen bonds...
September 26, 2016: Future Medicinal Chemistry
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