Design, synthesis, and biological evaluation of 1 ‐ethyl‐3‐(thiazol‐2‐yl)urea derivatives as Escherichia coli DNA gyrase inhibitors
Abstract
Discovery of novel DNA gyrase B inhibitors remains an attractive field in the search for new antibacterial drugs to overcome the known bacterial resistance mechanisms. In the present study, we designed and synthesized novel ethylurea derivatives of 4,5,6,7‐tetrahydrobenzo[1,2‐d]thiazole‐2,6‐diamine, 2‐(2‐aminothiazol‐4‐yl)acetic acid, and benzo[1,2‐d]thiazole‐2,6‐diamine and evaluated their Escherichia coli DNA gyrase inhibition. The most potent DNA gyrase inhibitors in the prepared library of compounds were benzo[1,2‐d]thiazoles 32–34, 36, and 37 with IC50 values in the low micromolar ra...
Source: Archiv der Pharmazie - December 1, 2017 Category: Drugs & Pharmacology Authors: Tihomir Toma šič, Michaela Barančoková, Nace Zidar, Janez Ilaš, Päivi Tammela, Danijel Kikelj Tags: FULL PAPER Source Type: research
Solid ‐phase organic synthesis of chiral, non‐racemic 1,2,4‐trisubstituted 1,4‐diazepanes with high σ1 receptor affinity
Abstract
The aim of this work was to transfer the established chiral‐pool synthesis of 1,2,4‐trisubstituted 1,4‐diazepanes in solution on the solid phase. For this purpose, (S)‐configured amino acids, (S)‐alanine, and (S)‐leucine, with a small methyl and a larger isobutyl moiety were attached to the solid support 9 by reductive amination. After five reaction steps on the solid support, the 1,4‐diazepanes (S)‐19a,b were cleaved off and reductively alkylated to afford the 1,2,4‐trisubstituted 1,4‐diazepanes (S)‐20a and (S)‐21b, respectively. Both compounds show high σ1 affinity and selectivity over t...
Source: Archiv der Pharmazie - December 1, 2017 Category: Drugs & Pharmacology Authors: Lena Fanter, Dirk Schepmann, Bernhard W ünsch Tags: FULL PAPER Source Type: research
Design, synthesis, in silico and antiproliferative evaluation of novel pyrazole derivatives as VEGFR ‐2 inhibitors
Abstract
As the blockade of the VEGFR‐2 signaling pathway is a viable approach in cancer therapy, the present study focuses on a series of pyrazole based VEGFR‐2 inhibitors that were designed on the basis of the hybridization approach, supported by docking and in silico computational studies. The designed compounds were synthesized through facile synthetic methods and the structures were confirmed by 1H NMR, 13C NMR, MS and elemental analysis. The compounds were screened for in vitro antiproliferative activity against the HT‐29 (human colon cancer) and MCF‐7 (human breast cancer) cell lines by MTT assay. The compou...
Source: Archiv der Pharmazie - December 1, 2017 Category: Drugs & Pharmacology Authors: Parameshwar Ravula, Harinadha Babu Vamaraju, Manichandrika Paturi, Janivara Nanjunde Gowda Narendra Sharath Chandra Tags: FULL PAPER Source Type: research
Editorial Board: Arch. Pharm. Chem. Life Sci. (12/2017)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - December 1, 2017 Category: Drugs & Pharmacology Tags: Editorial Board Source Type: research
Cover Picture: Arch. Pharm. Chem. Life Sci. (12/2017)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - December 1, 2017 Category: Drugs & Pharmacology Tags: Cover Picture Source Type: research
Rational Optimization of Tumor Suppressor ‐Derived Peptide Inhibitor Selectivity between Oncogene Tyrosine Kinases ErbB1 and ErbB2
The tumor‐suppressor protein Mig‐6 has been found to directly target and inhibit the human ErbB receptor tyrosine kinases ErbB1 and ErbB2. Despite their highly homologous nature, these two kinases are separately involved in the development of different types of human cancer. Here, we utilized a rational strategy to iteratively optimize the interaction specificity of the two kinases with a Mig‐6 derived peptide by exploiting structural diversity space. Instead of traditionally improving the peptide binding potency, the optimization attempts to maximize the affinity difference between peptides binding to ErbB1 and ErbB...
Source: Archiv der Pharmazie - November 13, 2017 Category: Drugs & Pharmacology Authors: Yilin Deng, Jian Li Tags: Full Paper Source Type: research
Editorial Board: Arch. Pharm. Chem. Life Sci. (11/2017)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - November 2, 2017 Category: Drugs & Pharmacology Tags: Editorial Board Source Type: research
Cover Picture: Arch. Pharm. Chem. Life Sci. (11/2017)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - November 2, 2017 Category: Drugs & Pharmacology Tags: Cover Picture Source Type: research
Novel pyridine ‐2,4,6‐tricarbohydrazide thiourea compounds as small key organic molecules for the potential treatment of type‐2 diabetes mellitus: In vitro studies against yeast α‐ and β‐glucosidase and in silico molecular modeling
Abstract
A range of novel pyridine‐2,4,6‐tricarbohydrazide thiourea compounds (4a–i) were synthesized in good to excellent yields (63–92%). The enzyme inhibitory potentials of these compounds were investigated against α‐ and β‐glucosidases because these enzymes play a crucial role in treating type‐2 diabetes mellitus (T2DM). As compared to the reference compound acarbose (IC50 38.22 ± 0.12 μM), compounds 4i (IC50 25.49 ± 0.67 μM), 4f (IC50 28.91 ± 0.43 μM), 4h (IC50 30.66 ± 0.52 μM), and 4e (IC50 35.01 ± 0.45 μM) delivered better inhibition against α‐glucosidase an...
Source: Archiv der Pharmazie - November 1, 2017 Category: Drugs & Pharmacology Authors: Tanzeel Ur. Rehman, Sadaf Riaz, Islam Ullah Khan, Muhammad Ashraf, Marek Bajda, Alicja Gawalska, Muhammad Yar Tags: FULL PAPER Source Type: research
6 ‐Nitroazolo[1,5‐a]pyrimidin‐7(4H)‐ones as Antidiabetic Agents
Prevention of the formation of advanced glycation end‐products (AGEs) is a reliable approach to achieve control over hyperglycemia and the associated pathogenesis of diabetic vascular complications. In these terms, new synthetic approaches to 6‐nitroazolo[1,5‐a]pyrimidines have been developed on the basis of the promising antiglycation activity of their structural analogues, such as azolo[5,1‐c][1,2,4]triazine‐4(1H)‐ones. A number of nitroazolopyrimidines were obtained by using nitration, chlorodeoxygenation, and amination reactions, and their antidiabetic properties were elucidated in vitro. It was shown that ...
Source: Archiv der Pharmazie - November 1, 2017 Category: Drugs & Pharmacology Authors: Alexander A. Spasov, Denis A. Babkov, Valentina A. Sysoeva, Roman A. Litvinov, Darya D. Shamshina, Evgeny N. Ulomsky, Konstantin V. Savateev, Viktor V. Fedotov, Pavel A. Slepukhin, Oleg N. Chupakhin, Valery N. Charushin, Vladimir L. Rusinov Tags: Full Paper Source Type: research
Synthesis, antitumor activity evaluation, and DNA ‐binding study of coumarin‐based agents
Abstract
A novel series of coumarin‐thiadiazole heterocycle derivatives was synthesized by the nucleophilic substitution reaction. The synthesized compounds were structurally verified by IR, 1H NMR, 13C NMR, mass spectra, and elemental analyses. The antitumor activity of the synthesized compounds was evaluated through DNA binding assays and the 60‐cell line panel according to the US NCI‐DTP protocol or a selection of human tumor cell lines: breast cancer (MCF‐7), liver cancer (HepG‐2), and colorectal cancer (HCT‐116). Most of the compounds had better DNA/ethidium bromide fluorescence quenching rather than methy...
Source: Archiv der Pharmazie - November 1, 2017 Category: Drugs & Pharmacology Authors: Kamilia M. Amin, Aly M. Taha, Riham F. George, Nada M. Mohamed, Fardous F. Elsenduny Tags: FULL PAPER Source Type: research
2 ‐Alkylsulfanyl‐4(5)‐aryl‐5(4)‐heteroarylimidazoles: An Overview on Synthetic Strategies and Biological Activity
2‐Alkylsulfanyl‐4(5)‐aryl‐5(4)‐heteroarylimidazoles represent an important class of ATP‐competitive protein kinase inhibitors, offering the possibility of multiple interactions with different regions of the target enzyme. The necessity of exploring the effects of diverse chemical decorations around the imidazole core prompted the design of several synthetic routes aimed at achieving both efficiency and flexibility. Additionally, the optimization of established protocols and the extensive use of transition metal‐catalyzed cross‐coupling reactions have been broadening the spectrum of preparative methodologies...
Source: Archiv der Pharmazie - November 1, 2017 Category: Drugs & Pharmacology Authors: Pierre Koch, Francesco Ansideri Tags: Review Article Source Type: research
Synthesis and Carbonic Anhydrase Inhibition of Tetrabromo Chalcone Derivatives
In the present study, human carbonic anhydrase (hCA) enzyme was purified and characterized from fresh blood human red cells by Sepharose‐4B‐l‐tyrosine‐sulfanilamide affinity gel chromatography. Secondly, a series of new tetrabromo chalcone derivatives containing 4,7‐methanoisoindol‐1,3‐dione (2a–i) were synthesized from the addition of Br2 to related chalcone derivatives (1a–i). The structures of the new molecules (2a–i) were confirmed by means of 1H NMR, 13C NMR and elemental analysis. Finally, the inhibitory effects of 2a–i on CA activities were investigated using the esterase method under in vitro ...
Source: Archiv der Pharmazie - November 1, 2017 Category: Drugs & Pharmacology Authors: Umit M. Kocyigit, Yakup Budak, Fikret Elig üzel, Parham Taslimi, Deryanur Kılıç, İlhami Gulçin, Mustafa Ceylan Tags: Full Paper Source Type: research
Design, Synthesis, Molecular Docking, and Anticancer Activity of Phthalazine Derivatives as VEGFR ‐2 Inhibitors
Novel series of phthalazine derivatives 6–11 were designed, synthesized, and evaluated for their anticancer activity against two human tumor cell lines, HCT‐116 human colon adenocarcinoma and MCF‐7 breast cancer cells, targeting the VEGFR‐2 enzyme. Compounds 7a,b and 8b,c showed the highest anticancer activities against both HCT116 human colon adenocarcinoma cells with IC50 of 6.04 ± 0.30, 13.22 ± 0.22, 18 ± 0.20, and 35 ± 0.45 μM, respectively, and MCF‐7 breast cancer cells with IC50 of 8.8 ± 0.45, 17.9 ± 0.50, 25.2 ± 0.55, and 44.3 ± 0.49 μM, respectively, in compar...
Source: Archiv der Pharmazie - November 1, 2017 Category: Drugs & Pharmacology Authors: Abdel ‐Ghany A. El‐Helby, Rezk R. A. Ayyad, Helmy Sakr, Khaled El‐Adl, Mamdouh M. Ali, Fathalla Khedr Tags: Full Paper Source Type: research
Synthesis, Biological Evaluation, and Molecular Modeling Study of Substituted Benzyl Benzamides as CETP Inhibitors
Cardiovascular disease is the most common cause for mortality and morbidity in the developed world; its risk is inversely related to the high‐density lipoprotein (HDL) cholesterol levels. Therefore, there is a great interest in developing new cholesteryl ester transfer protein (CETP) inhibitors capable of raising HDL as a novel approach for the prevention of cardiovascular disease. Herein, the synthesis and characterization of ten benzyl benzamides 8a–j that aim at CETP inhibition was performed. The in vitro CETP inhibition bioassay revealed that benzamide 8j had the best activity, with a percent inhibition of 82.2% at...
Source: Archiv der Pharmazie - November 1, 2017 Category: Drugs & Pharmacology Authors: Reema Abu Khalaf, Dima Sabbah, Eveen Al ‐Shalabi, Samar Bishtawi, Ghadeer Albadawi, Ghassan Abu Sheikha Tags: Full Paper Source Type: research
