1,708 results match your criteria Future Medicinal Chemistry [Journal]


NBGNU: a hypoxia-activated tripartite combi-nitrosourea prodrug overcoming AGT-mediated chemoresistance.

Future Med Chem 2018 Dec 18. Epub 2018 Dec 18.

Beijing Key Laboratory of Environmental & Virus Oncology, College of Life Science & Bioengineering, Beijing University of Technology, Beijing 100124, PR China.

Aim: A hypoxia-activated combi-nitrosourea prodrug, N-(2-chloroethyl)-N'-2-(2-(4-nitrobenzylcarbamate)-O -benzyl-9-guanine)ethyl-N-nitrosourea (NBGNU), was synthesized and evaluated for its hypoxic selectivity and anticancer activity in vitro.

Results: The prodrug was designed as a tripartite molecule consisting of a chloroethylnitrosourea pharmacophore to induce DNA interstrand crosslinks (ICLs) and an O -benzylguanine analog moiety masked by a 4-nitrobenzylcarbamate group to induce hypoxia-activated inhibition of O -alkylguanine-DNA alkyltransferase. NBGNU was tested for hypoxic selectivity, cytotoxicity and DNA ICLs ability. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0511DOI Listing
December 2018

Overcoming the emerging drug resistance of smoothened: an overview of small-molecule SMO antagonists with antiresistance activity.

Future Med Chem 2018 Dec 17;10(24):2855-2875. Epub 2018 Dec 17.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Ji'nan 250012, PR China.

Hedgehog (HH) signaling pathway plays vital roles in controlling embryonic cell fate and homeostatic, and becomes dormant in mature individuals, aberrant activation of HH signaling pathway is involved in a number of human cancers. Smoothened (SMO), a vital transducer of HH signaling pathway, attracts significant attentions in HH signaling pathway-related cancer therapy. The approval of SMO antagonists vismodegib proves that SMO is a promising therapeutic target, and a number of SMO antagonists are reported since then. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0200DOI Listing
December 2018

Discovery of CDK4 inhibitors by convolutional neural networks.

Future Med Chem 2018 Dec 17. Epub 2018 Dec 17.

Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, PR China.

Aim: Descriptors of molecules are important in the discovery of lead compounds. Most of these descriptors are used to represent molecular structures, although structural formulas are the most intuitive representation. Convolutional neural networks (ConvNets) are effective for managing intuitive information. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0478DOI Listing
December 2018

Sialic acid as a target for the development of novel antiangiogenic strategies.

Future Med Chem 2018 Dec 12;10(24):2835-2854. Epub 2018 Dec 12.

Section of Experimental Oncology & Immunology, Department of Molecular & Translational Medicine (DMTM), University of Brescia, Brescia 25123, Italy.

Sialic acid is associated with glycoproteins and gangliosides of eukaryotic cells. It regulates various molecular interactions, being implicated in inflammation and cancer, where its expression is regulated by sialyltransferases and sialidases. Angiogenesis, the formation of new capillaries, takes place during inflammation and cancer, and represents the outcome of several interactions occurring at the endothelial surface among angiogenic growth factors, inhibitors, receptors, gangliosides and cell-adhesion molecules. Read More

View Article

Download full-text PDF

Source
https://www.future-science.com/doi/10.4155/fmc-2018-0298
Publisher Site
http://dx.doi.org/10.4155/fmc-2018-0298DOI Listing
December 2018
1 Read

Design and synthesis of some β-carboline derivatives as multi-target anticancer agents.

Future Med Chem 2018 Dec 12;10(24):2791-2814. Epub 2018 Dec 12.

Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.

Aim: Some anticancer β-carbolines exhibited dual inhibition of topo-I and KSP.

Methodology/results: Novel β-carbolines were synthesized and screened for their anticancer activity according to the NCI protocol. Five dose assays results indicated that compounds 9, 10, 12, 17 and 20 were potent and non selective anticancer agents; the sulfanyltriazole 12 was the most potent. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0226DOI Listing
December 2018

Computational chemical biology on the rise.

Future Med Chem 2019 Jan 10;11(1):1-3. Epub 2018 Dec 10.

Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology & Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Endenicher Allee 19c, D-53115 Bonn, Germany.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0282DOI Listing
January 2019

Carbon monoxide and its donors - their implications for medicine.

Future Med Chem 2019 Jan 11;11(1):61-73. Epub 2018 Dec 11.

Department of General Biochemistry, Faculty of Biology & Environmental Protection, University of Lodz, Pomorska 141/3, 90-236 Lodz, Poland.

Inhalation of high concentrations of carbon monoxide (CO) is known to lead to serious systemic complications and neuronal disturbances. However, it has been found that not only is CO produced endogenously, but also that low concentrations can bestow beneficial effects which may be of interest in biology and medicine. As translocation of CO through the human organism is difficult, small molecules known as CO-releasing molecules (CORMs) deliver controlled amounts of CO to biological systems, and these are of great interest from a medical point of view. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0215DOI Listing
January 2019

Consensus anticancer activity profiles derived from the meta-analysis of reference compounds for widely used cell lines.

Future Med Chem 2019 Jan 11;11(1):33-42. Epub 2018 Dec 11.

Molecular Medicine & Therapeutics Laboratory, CPMB, Osmania University, Hyderabad 500007, India.

Aim: To establish a standard reference for bioactivity of widely used anticancer compounds that might be useful for meaningful interpretation of the cell viability data generated for novel synthetic derivatives.

Materials & Methods: Meta-analysis of published IC50 values was carried out for commonly used anticancer compounds and cell viability experiments were performed to validate the role of certain factors in drug activity.

Results & Conclusion: Variability in the published IC50 values was demonstrated. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0303DOI Listing
January 2019

How dynamic docking simulations can help to tackle tough drug targets.

Future Med Chem 2018 Dec 10;10(24):2763-2765. Epub 2018 Dec 10.

Department of Pharmacy & Biotechnology, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0295DOI Listing
December 2018

Discovery of arginine-containing tripeptides as a new class of pancreatic lipase inhibitors.

Future Med Chem 2019 Jan 11;11(1):5-19. Epub 2018 Dec 11.

Department of Pharmacy, G. d'Annunzio University of Chieti-Pescara, Chieti, 66100 Italy.

Aim: The inhibition of pancreatic lipase (PL) represents one of the most promising strategies in the search for novel antiobesity drugs. We propose here a pioneering course by exploring tripeptide scaffolds in the way to selective PL inhibitors.

Methodology/results: The peptide series exhibited good PL inhibitory properties in vitro, with all the strongest inhibitors sharing a central arginine, shown in silico to be relevant for the active site-directed activity. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0216DOI Listing
January 2019

Synthesis, antiproliferative activity and 2D-QSAR study of some 8-alkyl-2,4-bisbenzylidene-3-nortropinones.

Future Med Chem 2018 Dec 10;10(24):2815-2833. Epub 2018 Dec 10.

Institute of Pharmacy and Molecular Biotechnology, INF364, Heidelberg University, D-69120 Heidelberg, Germany.

Aim: Colon cancer is the third leading cause of death worldwide; therefore, there is a need for an effective therapy with lower side effects.

Methods: A series of 8-alkyl-2,4-bisbenzylidene-3-nortropinones 3 & 14-39 was prepared via Claisen-Schmidt condensation of 8-alkyl-3-nortropinones 11-13 with different aromatic aldehydes. The target compounds were screened for their antiproliferative activity. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0205DOI Listing
December 2018

Glycans in nanomedicine, impact and perspectives.

Future Med Chem 2019 Jan 11;11(1):43-60. Epub 2018 Dec 11.

Department of Biotechnology & Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy.

Glycans have been selected by nature for both structural and 'recognition' purposes. Taking inspiration from nature, nanomedicine exploits glycans not only as structural constituents of nanoparticles and nanostructured biomaterials but also as selective interactors of such glyco-nanotools. Surface glycosylation of nanoparticles finds application in targeting specific cells, whereas recent findings give evidence that the glycan content of cell microenvironment is able to induce the cell fate. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0368DOI Listing
January 2019

Green synthesis and biological activity of silver-curcumin nanoconjugates.

Future Med Chem 2018 Nov 11;10(22):2577-2588. Epub 2018 Dec 11.

National Institute of Laser Enhanced Sciences (NILE), Cairo University, Giza 12613, Egypt.

Aim: There is an urgent need to develop alternative antimicrobial agents and, one of which is via the use of nanotechnology. Green synthetic routes are recently being replaced for nanoparticles preparation. Methods results: Silver-curcumin nanoconjugates (Ag-CurNCs) were prepared in an eco-friendly method. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0152DOI Listing
November 2018

Novel non-nucleotidic STING agonists for cancer immunotherapy.

Future Med Chem 2018 Dec 10;10(24):2767-2769. Epub 2018 Dec 10.

Department of Neurosurgery, Harvey Cushing Neuro-Oncology Laboratories, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0367DOI Listing
December 2018

One-pot synthesis of spiro(indoline-3,4'-pyrazolo[3,4-b]pyridine)-5'-carbonitriles as p53-MDM2 interaction inhibitors.

Future Med Chem 2018 Dec 10;10(24):2771-2789. Epub 2018 Dec 10.

Department of Applied Organic Chemistry Department, National Research Center, Dokki, Cairo 12622, Egypt.

Aim: Inhibition of P53-mdm2 interaction will lead to cancer cell apoptosis. This strategy was achieved by reported spiro-oxindole derivatives.

Materials & Methods: Spiro(indoline-3,4'-pyrazolo[3,4-b]pyridine)-5'-carbonitrile derivatives (4a-i and 9a, b) were synthesized and screened for their in vitro anticancer activity. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0288DOI Listing
December 2018

The synthesis and biological evaluation of a new bioactive metabolite of mosapride as a potential gastroprokinetic agent.

Future Med Chem 2019 Jan 11;11(1):21-32. Epub 2018 Dec 11.

Key Laboratory of New Drugs Design & Discovery of Liaoning Province, Shenyang Pharmaceutical University, Shenyang, PR China.

Aim: To synthesize the new bioactive metabolites of mosapride (R)-N-[2-hydroxy-3-(4-fluorobenzyl)amino]-propyl-5-chlorine-4-amino-2-ethoxyben-zamide (R-isomer) and (S)-N-[2-hydroxy-3-(4-fluorobenzyl)amino]-propyl-5-chlorine-4-amino-2-ethoxybenzamide (S-isomer) and evaluate their in vitro and in vivo pharmacological and pharmacokinetic profiles.

Results: S-isomer as a gastroprokinetic agent showed significant pharmacological activities in vivo. Furthermore, compared with the EC values for R-isomer and mosapride, S-isomer was proven to generate the same 5-HT receptor agonistic activity with a smaller amount. Read More

View Article

Download full-text PDF

Source
https://www.future-science.com/doi/10.4155/fmc-2018-0243
Publisher Site
http://dx.doi.org/10.4155/fmc-2018-0243DOI Listing
January 2019
1 Read

A computational and experimental study to develop E-selectin targeted peptides for molecular imaging applications.

Future Med Chem 2018 Dec 6. Epub 2018 Dec 6.

Aix Marseille Univ, CNRS, Cent Marseille, ISM2, Marseille, France.

Aim: E-selectin is overexpressed on angiogenic and inflamed endothelium. Molecules binding to E-selectin with high affinity and specificity enable its use as a molecular imaging biomarker.

Material & Methods: The interactions of four different peptides (i. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0244DOI Listing
December 2018
1 Read

Matriptase-2: monitoring and inhibiting its proteolytic activity.

Future Med Chem 2018 Dec 6. Epub 2018 Dec 6.

Department of Molecular Biochemistry, Faculty of Chemistry, University of Gdansk, ul. Wita Stwosza 63, 80-308 Gdansk, Poland.

Matriptase-2 (MT2) is a membrane-anchored proteolytic enzyme. It acts as the proteolytic key regulator in human iron homeostasis. A high expression level can lead to iron overload diseases, whereas mutations in the gene encoding MT2, TMPRSS6, may result in various forms of iron deficiency anemia. Read More

View Article

Download full-text PDF

Source
https://www.future-science.com/doi/10.4155/fmc-2018-0346
Publisher Site
http://dx.doi.org/10.4155/fmc-2018-0346DOI Listing
December 2018
4 Reads

Smart fluorescent probes for in situ imaging of enzyme activity: design strategies and applications.

Future Med Chem 2018 Dec 6. Epub 2018 Dec 6.

School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, 693 Xiongchu Avenue, Wuhan 430073, PR China.

Enzymes play critical roles in the physiological and pathological processes of living systems. To provide detailed pictures of enzyme activity at the molecular and cellular levels, interdisciplinary studies of chemistry and biology have led to the emergence of many smart fluorescent probes, which emit fluorescence or show a shifted signal only upon interaction with their targets. With distinct advantage of a higher signal-to-noise ratio than traditional 'always on' probes, smart fluorescent probes enable sensitive detection of enzymes with clinical significance. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0193DOI Listing
December 2018

Anti-inflammatory indomethacin analogs endowed with preferential COX-2 inhibitory activity.

Future Med Chem 2018 Dec 6. Epub 2018 Dec 6.

Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.

Aim: The undeniable indomethacin potency has always suffered serious obstacles such as gastric damage. Continuous attempts to develop potent yet safe indomethacin analogs have never ceased.

Results: Herein are new indole derivatives 4a-h and 5a-c, which were synthesized via Fisher indole reaction, evaluated for both their in vivo anti-inflammatory activities using rat paw edema method and their in vitro cyclooxygenase inhibitory activities. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0224DOI Listing
December 2018
1 Read

A survey of the role of nitrile groups in protein-ligand interactions.

Future Med Chem 2018 Dec 6;10(23):2713-2728. Epub 2018 Dec 6.

National Institute of Biological Sciences, Beijing, No. 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, PR China.

In classical medicinal chemistry, nitrile groups were commonly considered as bioisosteres of carbonyl, hydroxyl and carboxyl groups, as well as halogen atoms. However, there is a lack of in-depth understanding about the structural and energetic characteristics of nitrile groups in protein-ligand interactions. Here, we have surveyed the Protein Data Bank and ChEMBL databases with the goal of characterizing such protein-ligand interactions for nitrile-containing compounds. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0252DOI Listing
December 2018

Dopamine receptor heteromers: biasing antipsychotics.

Future Med Chem 2018 Dec 6. Epub 2018 Dec 6.

Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Facultat de Medicina i Ciències de la Salut, IDIBELL-Universitat de Barcelona, L'Hospitalet de Llobregat, Spain.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0335DOI Listing
December 2018

The lipid peroxidation in patients with nephrolithiasis before and after extracorporeal shock wave lithotripsy.

Future Med Chem 2018 Dec 6;10(23):2685-2693. Epub 2018 Dec 6.

Department of General Biochemistry, Faculty of Biology & Environmental Protection, University of Łódź, Pomorska 141/3, 90-236 Łódź, Poland.

Aim: To evaluate the level of lipid peroxidation in patients with nephrolithiasis before and after extracorporeal shock wave lithotripsy (ESWL).

Materials & Methods: Isoprostane concentration (8-isoPGF) was measured in urine, and thiobarbituric acid reactive substance production in serum and erythrocytes. In addition, the concentrations of selected compounds (uric acid, glucose and creatinine) were measured in serum. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0149DOI Listing
December 2018
1 Read

Networks for better drug discovery: making optimal use of existing chemical space.

Future Med Chem 2018 Dec 5. Epub 2018 Dec 5.

E-Therapeutics PLC, Long Hanborough, Oxfordshire, OX29 8LN, UK.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0265DOI Listing
December 2018
2 Reads

In vitro antiprotozoal activity of some medicinal plants against sleeping sickness, Chagas disease and leishmaniasis.

Future Med Chem 2018 Dec 4. Epub 2018 Dec 4.

Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr El-Ainy Street, Cairo, 11562, Egypt.

Aim: Antiprotozoal activity of 36 medicinal plants was evaluated.

Materials & Methods: In vitro potency against Trypanosoma brucei brucei, T. b. Read More

View Article

Download full-text PDF

Source
https://www.future-science.com/doi/10.4155/fmc-2018-0180
Publisher Site
http://dx.doi.org/10.4155/fmc-2018-0180DOI Listing
December 2018
4 Reads

A review of ligand-based virtual screening web tools and screening algorithms in large molecular databases in the age of big data.

Future Med Chem 2018 Nov 30;10(22):2641-2658. Epub 2018 Nov 30.

Bioinformatics & High Performance Computing Research Group (BIO-HPC), Computer Engineering Department. Universidad Católica San Antonio de Murcia (UCAM). Campus de los Jerónimos, 30107, Murcia, Spain.

Virtual screening has become a widely used technique for helping in drug discovery processes. The key to this success is its ability to aid in the identification of novel bioactive compounds by screening large molecular databases. Several web servers have emerged in the last few years supplying platforms to guide users in screening publicly accessible chemical databases in a reasonable time. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0076DOI Listing
November 2018
8 Reads

Critical examination of approaches exploited to assess the effectiveness of transmission-blocking drugs for malaria.

Future Med Chem 2018 Nov 30;10(22):2619-2639. Epub 2018 Nov 30.

ICMR-National Institute of Malaria Research, Dwarka, 110077, New Delhi, India.

In the absence of clinically proven vaccines and emerging resistance to common antimalarials and insecticides, the onus of interrupting the life cycle of Plasmodium falciparum, is upon the transmission-blocking drugs. Current transmission-blocking drug primaquine finds its use restricted because of associated hemolytic toxicity issues in Glucose-6-Phosphate-Dehydrogenase deficient individuals. This article provides an extensive review of the assays used by the investigators to evaluate the transmission-blocking activity of drugs. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0169DOI Listing
November 2018
5 Reads

Nanodelivery systems for overcoming limited transportation of therapeutic molecules through the blood-brain barrier.

Future Med Chem 2018 Nov 30;10(22):2659-2674. Epub 2018 Nov 30.

College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566, Republic of Korea.

Due to the impermeable structure and barrier function of the blood-brain barrier (BBB), the delivery of therapeutic molecules into the CNS is extremely limited. Nanodelivery systems are regarded as the most effective and versatile carriers for the CNS, as they can transport cargo molecules across the BBB via various mechanisms. This review emphasizes the multi-functionalization strategies of nanodelivery systems and combinatorial approaches for the delivery of therapeutic drugs and genes into the CNS. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0208DOI Listing
November 2018
1 Read

Synthesis and evaluation of steroidal thiazoline conjugates as potential antiviral agents.

Future Med Chem 2018 Nov 30. Epub 2018 Nov 30.

Key Laboratory of Fermentation Engineering (Ministry of Education), Institute of Biomedical & Pharmaceutical Sciences, Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Sino-German Biomedical Center, National '111' Center for Cellular Regulation & Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, PR China.

Aim: Many heterocyclic compounds derived from natural steroids exhibited broad activities, so this work focused on the investigations on a series of steroidal thiazoline conjugates as antiviral agents.

Materials & Methods:  A series of steroid derivatives containing thiazoline heterocycles were designed and synthesized via a convenient condensation procedure. The compounds were screened for their potential antivirus activities against Enterovirus 71 (EV71) and Coxsackie Virus Type B (CVB3). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0075DOI Listing
November 2018
3 Reads

The convergence of artificial intelligence and chemistry for improved drug discovery.

Future Med Chem 2018 Nov 30;10(22):2573-2576. Epub 2018 Nov 30.

Hit Discovery, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Cambridge, UK.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0161DOI Listing
November 2018

Antimicrobial peptides with antiprotozoal activity: current state and future perspectives.

Future Med Chem 2018 Nov 30;10(22):2569-2572. Epub 2018 Nov 30.

Department of Medicine & Surgery, Laboratory of Microbiology & Virology, University of Parma, Parma, Italy.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0460DOI Listing
November 2018

Traditional Tibetan medicinal plants: a highlighted resource for novel therapeutic compounds.

Future Med Chem 2018 Nov 30. Epub 2018 Nov 30.

Biotechnology Institute, School of Environment & Chemical Engineering, Dalian Jiaotong University, Dalian 116028, PR China.

Around 70-80% of drugs used in traditional Tibetan medicine (TTM) come from Qinghai Tibet Plateau, the majority of which are plants. The biological and medicinal culture diversity on Qinghai Tibet Plateau are amazing and constitute a less tapped resource for innovative drug research and development. Meanwhile, the problem of the exhausting Tibetan medicine resources is worrying. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0235DOI Listing
November 2018
3 Reads

Antimicrobial residues in animal products may induce Salmonella spp. resistance in humans.

Future Med Chem 2018 Nov 30. Epub 2018 Nov 30.

S-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, Mato Grosso do Sul, Brazil.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0247DOI Listing
November 2018

Synthesis, structural and antimicrobial studies of binary and ternary complexes of a new tridentate thiosemicarbazone.

Future Med Chem 2018 Nov 30;10(21):2507-2519. Epub 2018 Nov 30.

Elettra-Sincrotrone Trieste S.C.p.A., AREA Science Park, 34149 Basovizza, Trieste, Italy.

A new thiosemicarbazone ligand was synthesized and characterized using spectroscopic techniques (UV-Vis and IR) and synchrotron x-ray powder diffraction. With M = Mn, Zn and Cd, coordination compounds of the type (M[L]) were isolated. In the presence of sodium dithiocarbamate salts (NadiEtdtc. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0194DOI Listing
November 2018

Ligand-based drug design of novel aldose reductase inhibitors.

Future Med Chem 2018 Nov 30. Epub 2018 Nov 30.

Department of Biochemical Pharmacology, Center of Experimental Medicine SAS, Institute of Experimental Pharmacology & Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0127DOI Listing
November 2018

Discovery of 2-(aminopyrimidin-5-yl)-4-(morpholin-4-yl)-6- substituted triazine as PI3K and BRAF dual inhibitor.

Future Med Chem 2018 Oct 16;10(20):2445-2455. Epub 2018 Oct 16.

Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China.

Aim: The discovery and development of novel agents simultaneously targeting PI3K/AKT/mammalian target of rapamycin and Ras/RAF/MEK, two signaling pathways, are urgent to improve the curative effect of kinase inhibitors and overcome acquired resistance.

Methods/results: In the present study, 2-(2-aminopyrimidin-5-yl)-4-(morpholin-4-yl)-6-(N-cyclopropyl-N- (1-benzoylpiperidin-4-yl))triazines/pyrimidines were designed as PI3K and BRAF dual inhibitors. The synthesized 20 compounds exhibited potent antiproliferative effects in vitro against HCT116, A375, MCF-7, Colo205, A549 and LOVO cancer cell lines. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0145DOI Listing
October 2018
1 Read

Comparative evaluation of new dihydropyrimidine and dihydropyridine derivatives perturbing mitotic spindle formation.

Future Med Chem 2018 Oct 16;10(20):2395-2410. Epub 2018 Oct 16.

Department of Experimental & Clinical Pharmacology, Pomeranian Medical University, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland.

Aim: The mitotic spindle plays a key role in cell division which makes it an important target in cancer therapy. In the present study the antiproliferative activity of 4-benzyl-5-phenyl-3,4-dihydropyrimidine-2(1H)-thione (1) and its pyridine bioisoster (2) were evaluated and compared with monastrol (MON), the first known cell-permeable small molecule which disrupts bipolar spindle formation by inhibiting Eg5-kinesin activity.

Results: Our data revealed that compound 2 showed higher antiproliferative activity than MON against MCF7 and A375 cell lines and comparable reversible cell cycle inhibition in G2/M phase. Read More

View Article

Download full-text PDF

Source
https://www.future-science.com/doi/10.4155/fmc-2018-0094
Publisher Site
http://dx.doi.org/10.4155/fmc-2018-0094DOI Listing
October 2018
4 Reads

The emerging field of senotherapeutic drugs.

Future Med Chem 2018 Oct 16;10(20):2369-2372. Epub 2018 Oct 16.

Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Panepistimiopolis Zografou, Greece.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2018-0234DOI Listing
October 2018

New targets to modulate the DNA damage response.

Future Med Chem 2018 Oct 16;10(20):2377-2380. Epub 2018 Oct 16.

Experimental Therapeutics Program, IFOM-FIRC Institute of Molecular Oncology Foundation, Via Adamello, 16-20139 Milano, Italy.

View Article

Download full-text PDF

Source
https://www.future-science.com/doi/10.4155/fmc-2018-0231
Publisher Site
http://dx.doi.org/10.4155/fmc-2018-0231DOI Listing
October 2018
7 Reads

Making way for suppressing the FGF19/FGFR4 axis in cancer.

Future Med Chem 2018 Oct 16;10(20):2457-2470. Epub 2018 Oct 16.

Department of Oral Biology, Dental College of Georgia, Augusta University, Augusta, GA, USA.

FGF19 is a noncanonical FGF ligand that can control a broad spectrum of physiological responses, which include bile acid homeostasis, liver metabolism and glucose uptake. Many of these responses are mediated by FGF19 binding to its FGFR4/β-klotho receptor complex and controlling activation of an array of intracellular signaling events. Overactivation of the FGF19/FGFR4 axis has been implicated in tumorigenic formation, progression and metastasis, and inhibitors of this axis have recently been developed for single agent use or in combination with other anticancer drugs. Read More

View Article

Download full-text PDF

Source
https://www.future-science.com/doi/10.4155/fmc-2018-0099
Publisher Site
http://dx.doi.org/10.4155/fmc-2018-0099DOI Listing
October 2018
3 Reads

Nuclear magnetic resonance structure-based drug design.

Future Med Chem 2018 Oct 16;10(20):2373-2376. Epub 2018 Oct 16.

Laboratory of Physical Chemistry, ETH Zürich, Vladimir-Prelog-Weg 2, 8093 Zürich, Switzerland.

View Article

Download full-text PDF

Source
https://www.future-science.com/doi/10.4155/fmc-2018-0160
Publisher Site
http://dx.doi.org/10.4155/fmc-2018-0160DOI Listing
October 2018
3 Reads

Natural products and their derivatives as cyclooxygenase-2 inhibitors.

Future Med Chem 2018 Oct 16;10(20):2471-2492. Epub 2018 Oct 16.

Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga 142001, Punjab, India.

From ancient times, natural products have been continuously used as therapeutic agents in the treatment of various ailments. Many drugs from the natural origin are available in the market as potent medicines. Over expression of cyclooxygenase-2 (COX-2) enzyme is associated with various physical disorders like various types of inflammations associated with cardiovascular diseases or malignancies. Read More

View Article

Download full-text PDF

Source
https://www.future-science.com/doi/10.4155/fmc-2018-0120
Publisher Site
http://dx.doi.org/10.4155/fmc-2018-0120DOI Listing
October 2018
7 Reads

A facile consensus ranking approach enhances virtual screening robustness and identifies a cell-active DYRK1α inhibitor.

Future Med Chem 2018 Oct 16;10(20):2411-2430. Epub 2018 Oct 16.

Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Panepistimiopolis Zografou, 157 71 Athens, Greece.

Background: Virtual screening is vital for contemporary drug discovery but striking performance fluctuations are commonly encountered, thus hampering error-free use. Results and Methodology: A conceptual framework is suggested for combining screening algorithms characterized by orthogonality (docking-scoring calculations, 3D shape similarity, 2D fingerprint similarity) into a simple, efficient and expansible python-based consensus ranking scheme. An original experimental dataset is created for comparing individual screening methods versus the novel approach. Read More

View Article

Download full-text PDF

Source
https://www.future-science.com/doi/10.4155/fmc-2018-0198
Publisher Site
http://dx.doi.org/10.4155/fmc-2018-0198DOI Listing
October 2018
2 Reads
4.000 Impact Factor

Rational design of coumarin derivatives as antituberculosis agents.

Future Med Chem 2018 Oct 16;10(20):2431-2444. Epub 2018 Oct 16.

Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Hyderabad 500078, India.

Aim: A series of coumarin derivatives was designed as potential antituberculosis agents.

Results: The compounds were screened against active and dormant Mycobacterium tuberculosis (Mtb). Compounds 3k and 3n were found to have the most promising activity against replicating MtbH37Rv exhibiting minimum inhibitory concentration of 4. Read More

View Article

Download full-text PDF

Source
https://www.future-science.com/doi/10.4155/fmc-2018-0015
Publisher Site
http://dx.doi.org/10.4155/fmc-2018-0015DOI Listing
October 2018
5 Reads
4.000 Impact Factor

Targeting the mitochondrial apoptosis pathway by a newly synthesized COX-2 inhibitor in pediatric ALL lymphocytes.

Future Med Chem 2018 Oct 11;10(19):2277-2289. Epub 2018 Oct 11.

Department of Pharmacology & Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, 1991953381, Iran.

Aim: Acute lymphoblastic leukemia (ALL) is known as a barely curable malignancy. Particular mutations involved in apoptosis may have a main role in the onset of ALL in the pediatric patients. It has been proven that cycloxygenase-2 is capable of impairing the apoptosis pathway through mitochondria in tumor cells. Read More

View Article

Download full-text PDF

Source
https://www.future-science.com/doi/10.4155/fmc-2018-0032
Publisher Site
http://dx.doi.org/10.4155/fmc-2018-0032DOI Listing
October 2018
3 Reads

Deep learning and virtual drug screening.

Future Med Chem 2018 Oct 5. Epub 2018 Oct 5.

Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital & Harvard Medical School, Charlestown, MA 02129, USA.

Current drug development is still costly and slow given tremendous technological advancements in drug discovery and medicinal chemistry. Using machine learning (ML) to virtually screen compound libraries promises to fix this for generating drug leads more efficiently and accurately. Herein, we explain the broad basics and integration of both virtual screening (VS) and ML. Read More

View Article

Download full-text PDF

Source
https://www.future-science.com/doi/10.4155/fmc-2018-0314
Publisher Site
http://dx.doi.org/10.4155/fmc-2018-0314DOI Listing
October 2018
5 Reads

Synthesis and in vitro antioxidant activity of new pyrimidin/benzothiazol-substituted piperazinyl flavones.

Future Med Chem 2018 Oct;10(19):2293-2308

Pharmaceutical & Medicinal Chemistry Department, Pharmaceutical & Drug Industries Research Division, National Research Centre, Dokki, Giza 12622, Egypt.

Aim: Synthesis of novel 2(2-hydroxyphenyl) pyrimidine/benzothiazole piperazinyl-substituted flavones end evaluate their antioxidant activity.

Results: Six novel 2-(2-hydroxyphenyl) pyrimidine/benzothiazole-substituted flavones were synthesized, their structures were confirmed by elementary and spectral analyses. The compounds were evaluated for their in vitro antioxidant potency by employing various antioxidant assays. Read More

View Article

Download full-text PDF

Source
https://www.future-science.com/doi/10.4155/fmc-2018-0206
Publisher Site
http://dx.doi.org/10.4155/fmc-2018-0206DOI Listing
October 2018
1 Read

The development of protein tyrosine phosphatase1B inhibitors defined by binding sites in crystalline complexes.

Future Med Chem 2018 Oct;10(19):2345-2367

School of Chemistry & Pharmaceutical Engineering, Qilu University of Technology (Shandong Academy of Sciences), 3501 Daxue Road, Jinan 250353, PR China.

Protein tyrosine phosphatase1B (PTP1B), a significant negative regulator in insulin and leptin signaling pathways, has emerged as a promising drug target for Type II diabetes mellitus and obesity. Numerous potent PTP1B inhibitors have been discovered within both academia and pharmaceutical industry. However, nearly all medicinal chemistry efforts have been severely hindered because a vast majority of them demonstrate poor membrane permeability and low-selectivity, especially over T-cell protein tyrosine phosphatase (TCPTP). Read More

View Article

Download full-text PDF

Source
https://www.future-science.com/doi/10.4155/fmc-2018-0089
Publisher Site
http://dx.doi.org/10.4155/fmc-2018-0089DOI Listing
October 2018
4 Reads

Covalent simulations of covalent/irreversible enzyme inhibition in drug discovery: a reliable technical protocol.

Future Med Chem 2018 Oct;10(19):2265-2275

Molecular Bio-Computation & Drug Design Lab, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4000, South Africa.

Aim: Irreversible covalent inhibition of biological targets in disease pathogenesis is an emerging field in drug design. Computational techniques have assumed a critical role in understanding covalent enzyme inhibition. However, a gap currently exists with regards to the reliability and reproducibility of currently available protocols available in literature and open scientific forums. Read More

View Article

Download full-text PDF

Source
https://www.future-science.com/doi/10.4155/fmc-2017-0304
Publisher Site
http://dx.doi.org/10.4155/fmc-2017-0304DOI Listing
October 2018
2 Reads
4.000 Impact Factor

Phenolic fraction and nonpolar fraction from sea buckthorn leaves and twigs: chemical profile and biological activity.

Future Med Chem 2018 Oct 27;10(20):2381-2394. Epub 2018 Sep 27.

Department of Biochemistry, Institute of Soil Science & Plant Cultivation, State Research Institute, 24-100 Puławy, Poland.

Aim: The main objective of our studies was to determine the chemical composition and biological activities (antioxidant and anticoagulant properties) of two standardized phenolic fractions from sea buckthorn twig and leaf, and two standardized nonpolar fractions from twig and leaf in human plasma in vitro.

Material & Methods:  Appropriately prepared extracts from sea buckthorn twigs and leaves were used. Markers of oxidative stress and hemostasis were determined in this work. Read More

View Article

Download full-text PDF

Source
https://www.future-science.com/doi/10.4155/fmc-2018-0144
Publisher Site
http://dx.doi.org/10.4155/fmc-2018-0144DOI Listing
October 2018
6 Reads