Mannich Ketones as Possible Antimycobacterial Agents
Twenty‐three known unsaturated and fused Mannich ketones and their reduced derivatives (amino alcohols) were selected for an antituberculotic study. They were screened against several mycobacterial strains including Mycobacterium tuberculosis, M. xenopi, and M. gordonae, and minimum inhibitory concentration values were also determined using the standard antituberculotic drug isoniazid (INH) as a reference. Structure–activity relationships were also studied. The mode of action of the test compounds was investigated using transmission electron microscopy, high‐performance liquid chromatography, and matrix‐assisted de...
Source: Archiv der Pharmazie - July 1, 2017 Category: Drugs & Pharmacology Authors: Zsolt Lutz, Katalin Orb án, Ágnes Bóna, László Márk, Gábor Maász, László Prókai, Lázló Seress, Tamás Lóránd Tags: Full Paper Source Type: research
Fragment ‐Based Drug Discovery in the Bromodomain and Extra‐Terminal Domain Family
Bromodomain and extra‐terminal domain (BET) inhibition has emerged recently as a potential therapeutic target for the treatment of many human disorders such as atherosclerosis, inflammatory disorders, chronic obstructive pulmonary disease (COPD), some viral infections, and cancer. Since the discovery of the two potent inhibitors, I‐BET762 and JQ1, different research groups have used different techniques to develop novel potent and selective inhibitors. In this review, we will be concerned with the trials that used fragment‐based drug discovery (FBDD) approaches to discover or optimize BET inhibitors, also showing fra...
Source: Archiv der Pharmazie - July 1, 2017 Category: Drugs & Pharmacology Authors: Mostafa Radwan, Rabah Serya Tags: Review Article Source Type: research
Acetamide Derivatives of Chromen ‐2‐ones as Potent Cholinesterase Inhibitors
Alzheimer's disease (AD), a neurodegenerative disorder, is a serious medical issue worldwide with drastic social consequences. Inhibition of cholinesterase is one of the rational and effective approaches to retard the symptoms of AD and, hence, consistent efforts are being made to develop efficient anti‐cholinesterase agents. In pursuit of this, a series of 19 acetamide derivatives of chromen‐2‐ones were synthesized and evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potential. All the synthesized compounds exhibited significant anti‐AChE and anti‐BChE activity, with IC...
Source: Archiv der Pharmazie - July 1, 2017 Category: Drugs & Pharmacology Authors: Suchita Prasad, Bipul Kumar, Shiv Kumar, Karam Chand, Shashank S. Kamble, Hemant K. Gautam, Sunil K. Sharma Tags: Full Paper Source Type: research
Synthesis and Biological Evaluation of New Diarylpyrazole and Triarylimidazoline Derivatives as Selective COX ‐2 Inhibitors
New series of diarylpyrazoles 8a–f and triarylimidazoline‐5‐ones 11a–g were synthesized and evaluated for their in vitro cyclooxygenase‐1 (COX‐1) and COX‐2 inhibitory activity and in vivo anti‐inflammatory activity. The synthesized compounds showed good selectivity for COX‐2; compounds 8a, 8d, 8f, 11a, and 11c exhibited the highest COX‐2 selectivity indexes (SI = 4.77–5.43) compared to the reference drug celecoxib (SI = 7.8). All compounds showed good in vivo anti‐inflammatory activity, especially compounds 8a, 8f, 11c, and 11d, which also showed some similarities to the time interval patter...
Source: Archiv der Pharmazie - June 12, 2017 Category: Drugs & Pharmacology Authors: Khaled R.A. Abdellatif, Mohamed A. Abdelgawad, Madlen B. Labib, Taha H. Zidan Tags: Full Paper Source Type: research
Editorial Board: Arch. Pharm. Chem. Life Sci. (6/2017)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - June 6, 2017 Category: Drugs & Pharmacology Tags: Editorial Board Source Type: research
Cover Picture: Arch. Pharm. Chem. Life Sci. (6/2017)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - June 6, 2017 Category: Drugs & Pharmacology Tags: Cover Picture Source Type: research
Isophthalic Acid ‐Based HDAC Inhibitors as Potent Inhibitors of HDAC8 from Schistosoma mansoni
Schistosoma mansoni histone deacetylase 8 (SmHDAC8) has been recently identified as a new potential target for the treatment of schistosomiasis. A series of newly designed and synthesized alkoxyamide‐based and hydrazide‐based HDAC inhibitors were tested for inhibitory activity against SmHDAC8 and human HDACs 1, 6, and 8. The front runner compounds showed submicromolar activity against SmHDAC8 and modest preference for SmHDAC8 over its human orthologue hHDAC8. Docking studies provided insights into the putative binding mode in SmHDAC8 and allowed rationalization of the observed selectivity profile.
A series of newly de...
Source: Archiv der Pharmazie - June 1, 2017 Category: Drugs & Pharmacology Authors: Katharina Stenzel, Alokta Chakrabarti, Jelena Melesina, Finn K. Hansen, Julien Lancelot, Simon Herkenh öhner, Beate Lungerich, Martin Marek, Christophe Romier, Raymond. J. Pierce, Wolfgang Sippl, Manfred Jung, Thomas Kurz Tags: Full Paper Source Type: research
Design, Synthesis, and Biological Evaluation of Isothiosemicarbazones with Antimycobacterial Activity
A series of benzaldehyde and salicylaldehyde‐S‐benzylisothiosemicarbazones was synthesized and tested against 12 different strains of mycobacteria, Gram‐positive and Gram‐negative bacteria, and the significant selectivity toward mycobacteria was proved. Twenty‐eight derivatives were evaluated for the inhibition of isocitrate lyase, which is a key enzyme of the glyoxylate cycle necessary for latent tuberculosis infection, and their iron‐chelating properties were investigated. Two derivatives, 5‐bromosalicylaldehyde‐S‐(4‐fluorobenzyl)‐isothiosemicarbazone and salicylaldehyde‐S‐(4‐bromobenzyl)‐is...
Source: Archiv der Pharmazie - June 1, 2017 Category: Drugs & Pharmacology Authors: Eva Novotn á, Karel Waisser, Jiří Kuneš, Karel Palát, Lenka Skálová, Barbora Szotáková, Vladimír Buchta, Jiřina Stolaříková, Vít Ulmann, Marcela Pávová, Jan Weber, Jitka Komrsková, Pavlína Hašková, Ivan Vokřál, Vladimír Wsól Tags: Full Paper Source Type: research
Design, Synthesis, and Evaluation of Novel Tyrosine ‐Based DNA Gyrase B Inhibitors
The discovery and synthesis of new tyrosine‐based inhibitors of DNA gyrase B (GyrB), which target its ATPase subunit, is reported. Twenty‐four compounds were synthesized and evaluated for activity against DNA gyrase and DNA topoisomerase IV. The antibacterial properties of selected GyrB inhibitors were demonstrated by their activity against Staphylococcus aureus and Enterococcus faecalis in the low micromolar range. The most promising compounds, 8a and 13e, inhibited Escherichia coli and S. aureus GyrB with IC50 values of 40 and 30 µM. The same compound also inhibited the growth of S. aureus and E. faecalis with min...
Source: Archiv der Pharmazie - June 1, 2017 Category: Drugs & Pharmacology Authors: Andrej E. Cotman, Marko Trampu ž, Matjaž Brvar, Danijel Kikelj, Janez Ilaš, Lucija Peterlin‐Mašič, Sofia Montalvão, Päivi Tammela, Rok Frlan Tags: Full Paper Source Type: research
Synthesis and Antiproliferative Activity of Thioxoflavones Mannich Base Derivatives
Two series of 12 novel thioxoflavones Mannich base derivatives 5a–f and 6a–f were synthesized via Mannich reaction of 4′,7‐dimethoxy‐5‐hydroxyflavothione (3) or 3′,4′,7‐trimethoxy‐5‐hydroxyflavothione (4) with appropriate aliphatic amines or alicyclic amines and formaldehyde. Thioxoflavones 3 and 4 were prepared from 4′,7‐dimethoxy‐5‐hydroxyflavone (1) and 3′,4′,7‐trimethoxy‐5‐hydroxyflavone (2) with Lawesson's reagent, respectively. Their antiproliferative activities in vitro were evaluated on a panel of three human cell lines (HeLa, HCC1954, and SK‐OV‐3) by CCK‐8 assay. The r...
Source: Archiv der Pharmazie - June 1, 2017 Category: Drugs & Pharmacology Authors: Wei Li, Xueli Li, Manhui Liu, Qiuan Wang Tags: Full Paper Source Type: research
Design and Synthesis of 1,2,4 ‐Triazolo[3,2‐b]‐1,3,5‐thiadiazine Derivatives as a Novel Template for Analgesic/Anti‐Inflammatory Activity
Previously, we demonstrated that certain heterocyclic compounds derived from 3‐substituted‐1,2,4‐triazole‐5‐thiones had promising analgesic/anti‐inflammatory activities together with low ulcerogenic properties. Therefore, we sought to design and synthesize new derivatives of triazol‐5‐thiones‐fused heterocycles. In the present study, a series of novel bis‐Mannich bases, namely 2,6‐disubstituted‐6,7‐dihydro‐5H‐1,2,4‐triazolo[3,2‐b]‐1,3,5‐thiadiazines (1a–d, 2a–c, and 3a–d), were synthesized and characterized to assess their possible anti‐inflammatory/analgesic properties. Additi...
Source: Archiv der Pharmazie - June 1, 2017 Category: Drugs & Pharmacology Authors: Seyma Sert ‐Ozgur, Banu C. Tel, Elif I. Somuncuoglu, Inci Kazkayasi, Mevlut Ertan, Birsen Tozkoparan Tags: Full Paper Source Type: research
Three ‐Component Aminoalkylations Yielding Dihydronaphthoxazine‐Based Sirtuin Inhibitors: Scaffold Modification and Exploration of Space for Polar Side‐Chains
Nonpolar derivatives of heterocyclic aromatic screening hits like the non‐selective sirtuin inhibitor splitomicin tend to be poorly soluble in biological fluids. Unlike sp3‐rich natural products, flat aromatic compounds are prone to stacking and often difficult to optimize into leads with activity in cellular systems. The aim of this work was to identify anchor points for the introduction of sp3‐rich fragments with polar functional groups into the newly discovered active (IC50 = 5 μM) but nonpolar scaffold 1,2‐dihydro‐3H‐naphth[1,2‐e][1,3]oxazine‐3‐thione by a molecular modeling approach. Docking s...
Source: Archiv der Pharmazie - May 26, 2017 Category: Drugs & Pharmacology Authors: Steffen Vojacek, Katja Beese, Zayan Alhalabi, S ören Swyter, Anja Bodtke, Carola Schulzke, Manfred Jung, Wolfgang Sippl, Andreas Link Tags: Full Paper Source Type: research
Design, Synthesis, and Biological Evaluation of Coumarin –Triazole Hybrid Molecules as Potential Antitumor and Pancreatic Lipase Agents
The design, synthesis, and investigation of antitumor and anti‐lipase activities of some coumarin–triazole hybrid molecules are reported. The synthesis of these hybrid molecules was performed under microwave irradiation and conventional heating procedures. The newly synthesized hybrid molecules were investigated as inhibitors against four tumor cell lines (BT20 human breast carcinoma, SK‐Mel 128 melanoma, DU‐145 prostate carcinoma, and A549 lung carcinoma) and porcine pancreatic lipase (PPL). Most of these compounds showed notable antitumor activities against the tested tumor cell lines, and compounds 8i and 8l sho...
Source: Archiv der Pharmazie - May 22, 2017 Category: Drugs & Pharmacology Authors: Bahittin Kahveci, Fatih Y ılmaz, Emre Menteşe, Serdar Ülker Tags: Full Paper Source Type: research
Benzimidazole Scaffold as Anticancer Agent: Synthetic Approaches and Structure –Activity Relationship
Cancer, also known as malignant neoplasm, is a dreadful disease which involves abnormal cell growth having the potential to invade or spread to other parts of the body. Benzimidazole is an organic compound that is heterocyclic and aromatic in nature. It is a bicyclic compound formed by the fusion of the benzene and imidazole ring systems. It is an important pharmacophore and a privileged structure in medicinal chemistry. According to the World Health Organisation (2015 survey), one in six deaths is due to cancer around the globe, accounting for 8.8 million deaths of which 70% of the cases were from low‐ and middle‐inco...
Source: Archiv der Pharmazie - May 22, 2017 Category: Drugs & Pharmacology Authors: Neelima Shrivastava, Mohd. Javed Naim, Md. Jahangir Alam, Farah Nawaz, Shujauddin Ahmed, Ozair Alam Tags: Review Article Source Type: research
Editorial Board: Arch. Pharm. Chem. Life Sci. (5/2017)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - May 2, 2017 Category: Drugs & Pharmacology Tags: Editorial Board Source Type: research
