Medicinal Attributes of Thienopyrimidine Based Scaffold Targeting Tyrosine Kinases and Their Potential Anticancer Activities
Thienopyrimidines (TP), comprising a thiophene ring fused with pyrimidine, are famous bioisosteres to purines, an essential part of the human metabolome. This scaffold has become an interesting structural element in the development of pharmaceutical compounds, due to their wide spectrum applications as cytotoxic agents against different types of human cancer cell lines, cGMP phosphodiesterase inhibitors, and anti‐viral, anti‐inflammatory, and anti‐microbial agents. The structural similarity of this scaffold with adenine made it an excellent moiety to be used in the design of kinase inhibitors. This review focuses on ...
Source: Archiv der Pharmazie - October 13, 2017 Category: Drugs & Pharmacology Authors: Amna Ghith, Nasser S.M. Ismail, Khairia Youssef, Khaled A.M. Abouzid Tags: Review Article Source Type: research
Editorial Board: Arch. Pharm. Chem. Life Sci. (10/2017)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - October 2, 2017 Category: Drugs & Pharmacology Tags: Editorial Board Source Type: research
Cover Picture: Arch. Pharm. Chem. Life Sci. (10/2017)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - October 2, 2017 Category: Drugs & Pharmacology Tags: Cover Picture Source Type: research
Design, Synthesis, and Screening of Triazolopyrimidine –Pyrazole Hybrids as Potent Apoptotic Inducers
This study aimed at assessing the cytological and biochemical changes in testicular germ cells after the exposure to triazolopyrimidines in a dose‐ and time‐dependent manner. Histomorphological analysis, fluorescence assays, apoptosis quantification, and terminal deoxynucleotidyl transferase dUTP‐mediated nick‐end labeling (TUNEL) assays were performed to determine cytological changes, whereas thiobarbituric acid‐reactive substance (TBARS) and ferric reducing antioxidant power (FRAP) assays were carried out to measure the oxidative stress in triazolopyrimidines treated germ cells. The parallel use of these method...
Source: Archiv der Pharmazie - October 1, 2017 Category: Drugs & Pharmacology Authors: Raj Kamal, Vipan Kumar, Ravinder Kumar, Jitender K. Bhardwaj, Priyanka Saraf, Priya Kumari, Vikas Bhardwaj Tags: Full Paper Source Type: research
Practical Synthesis of α‐Amyrin, β‐Amyrin, and Lupeol: The Potential Natural Inhibitors of Human Oxidosqualene Cyclase
A practical synthesis of α‐amyrin (1), β‐amyrin (2), and lupeol (3) was accomplished in total yields of 32, 42, and 40% starting from easily available ursolic acid (4), oleanolic acid (5), and betulin (6), respectively. Remarkably, these three natural pentacyclic triterpenes exhibited potential inhibitory activity against human oxidosqualene cyclase.
A practical synthesis of α‐amyrin (1), β‐amyrin (2), and lupeol (3) was accomplished in total yields of 32, 42, and 40% starting from easily available ursolic acid, oleanolic acid, and botulin, respectively. These three natural pentacyclic triterpenes exhibited po...
Source: Archiv der Pharmazie - October 1, 2017 Category: Drugs & Pharmacology Authors: Dongyin Chen, Fengguo Xu, Pu Zhang, Jie Deng, Hongbin Sun, Xiaoan Wen, Jun Liu Tags: Full Paper Source Type: research
New Biguanides as Anti ‐Diabetic Agents, Part II: Synthesis and Anti‐Diabetic Properties Evaluation of 1‐Arylamidebiguanide Derivatives as Agents of Insulin Resistant Type II Diabetes
New 1‐arylamidebiguanide hydrochloride salts were synthesized via reaction of hydrazide derivatives with dicyandiamide in acidic medium. The structure of the obtained derivatives was characterized by spectroscopic and elemental analysis tools. The anti‐diabetic properties of the synthesized compounds were determined. Oral treatment of hyperglycemic rats with the synthesized biguanide derivatives showed a significant decrease of the elevated glucose in comparison with the anti‐diabetic standard drug, metformin. The effects of the synthesized biguanide derivatives on the diabetic properties regarding liver function enz...
Source: Archiv der Pharmazie - October 1, 2017 Category: Drugs & Pharmacology Authors: Wahid M. Basyouni, Samir Y. Abbas, Mohamed F. El Shehry, Khairy A.M. El ‐Bayouki, Hanan F. Aly, Azza Arafa, Mahmoud S. Soliman Tags: Full Paper Source Type: research
Design, Synthesis, and Biological Evaluation of New Peptide Analogues as Selective COX ‐2 Inhibitors
A new class of peptide derivatives possessing SO2Me and N3 pharmacophores at the para position of a phenyl ring bound to different aromatic amino acids were synthesized based on solid‐phase synthesis methodology, and evaluated as selective cyclooxygenase‐2 (COX‐2) inhibitors. One of the analogues, i.e., compound 2a as the representative of this series, was recognized as the highest selective COX‐2 inhibitor with a COX‐2 selectivity index of >500. The structure–activity relationships (SARs) acquired indicated that compound 2a containing a 4‐(methylsulfonyl)benzoyl group as a pharmacophore and tyrosine as a ...
Source: Archiv der Pharmazie - September 5, 2017 Category: Drugs & Pharmacology Authors: Mohammad A. Ahmaditaba, Soraya Shahosseini, Bahram Daraei, Afshin Zarghi, Mohammad H. Houshdar Tehrani Tags: Full Paper Source Type: research
Synthesis and Functional Investigations of Computer Designed Novel Cladribine ‐Like Compounds for the Treatment of Multiple Sclerosis
In this study, we computer designed, synthesized, and characterized two novel derivatives of 2‐CdA, K1–5d and K2–4c, and investigated their underlying mechanism of beneficial effect using the CCRF‐CEM and RAJI cell lines. For this purpose, we first determined their effect on MS and DNA damage and repair‐related gene expression profiles using custom arrays along with 2‐CdA treatment at non‐toxic doses. Then, we determined whether cells underwent apoptosis after treatment with 2‐CdA, K1–5d, and K2–4c in CCRF‐CEM and RAJI cells, using the DNA fragmentation assay. It was found that both derivatives modula...
Source: Archiv der Pharmazie - September 1, 2017 Category: Drugs & Pharmacology Authors: Serkan Yavuz, Aysu Çetin, Atilla Akdemir, Doğukan Doyduk, Ali Dişli, Gurbet Çelik Turgut, Alaattin Şen, Yılmaz Yıldırır Tags: Full Paper Source Type: research
Design and Synthesis of a Highly Selective JAK3 Inhibitor for the Treatment of Rheumatoid Arthritis
Selective inhibition of Janus kinase 3 (JAK3) has been identified as an important strategy for the treatment of autoimmune disorders. Based on the unique cysteine 909 residue (Cys909) of JAK3 at the gatekeeper position, we have developed a new irreversible covalent inhibitor, III‐4, which is highly potent and selective in targeting JAK3. Importantly, III‐4 selectively inhibited JAK3 (IC50 = 57 ± 1.21 nM) over other JAKs (IC50 > 10 µM) and Cys909 kinome members (IC50 > 1 µM). A cellular selectivity study also confirmed that III‐4 preferentially inhibited JAK3 over JAK1 in JAK/STAT signal...
Source: Archiv der Pharmazie - September 1, 2017 Category: Drugs & Pharmacology Authors: Linhong He, Heying Pei, Tingxuan Lan, Minghai Tang, Chufeng Zhang, Lijuan Chen Tags: Full Paper Source Type: research
Synthesis, Molecular Modeling, and Evaluation of Novel Sulfonylhydrazones as Acetylcholinesterase Inhibitors for Alzheimer's Disease
Alzheimer's disease (AD) is the most common type of dementia and related to the degeneration of hippocampal cholinergic neurons, which dramatically affects cognitive ability. Acetylcholinesterase (AChE) inhibitors are employed as drugs for AD therapy. Three series of sulfonylhydrazone compounds were designed, and their ability to inhibit AChE was evaluated. Fifteen compounds were synthesized and twelve of them had IC50 values of 0.64–51.09 μM. The preliminary structure–activity relationships indicated that the methylcatechol moiety and arylsulfonyl substituents generated better compounds than both the benzodioxole a...
Source: Archiv der Pharmazie - September 1, 2017 Category: Drugs & Pharmacology Authors: Thais B. Fernandes, Micael R. Cunha, Renata P. Sakata, Thalita M. Candido, Andr é R. Baby, Maurício T. Tavares, Euzébio G. Barbosa, Wanda P. Almeida, Roberto Parise‐Filho Tags: Full Paper Source Type: research
Evaluation of β‐Aminocarboxylic Acid Derivatives in Hippocampal Excitatory Synaptic Transmission
β‐Aminocarboxylic acid derivatives (LINS04 series) were screened with the aim to explore their potential functional role in excitatory synaptic transmission in the central nervous system. We used field recordings in rat hippocampal slices to investigate the effects of the LINS04 series on the synaptic transmission at hippocampal CA1 synapses. We found that LINS04008 and LINS04009 increase the size of the evoked field excitatory postsynaptic potential (EPSP) in a dose‐dependent manner. The concentration–response curve shows that the efficacy of LINS04008 is highest in the series (EC50 = 91.32 µM; maximum fEPSP...
Source: Archiv der Pharmazie - September 1, 2017 Category: Drugs & Pharmacology Authors: Daniela R. Oliveira, Cibele V. Luchez, Zuner A. Bortolotto, Jo ão P. S. Fernandes Tags: Full Paper Source Type: research
Design, Synthesis, and Pharmacological Screening of Pyridazinone Hybrids as Anticonvulsant Agents
A series of new hybrid benzimidazole containing pyridazinones derivatives were designed and synthesized in accordance with the pharmacophoric requirements essential for the anticonvulsant activity. The synthesized compounds were evaluated for anticonvulsant activity on mice by the gold standard maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ)‐induced seizure models. Among the compounds tested, SS‐4F showed significant anticonvulsant activity in both the screens with ED50 values of 25.10 and 85.33 mg/kg in the MES and scPTZ screens, respectively. Compound SS‐4F emerged as safer and effective an...
Source: Archiv der Pharmazie - September 1, 2017 Category: Drugs & Pharmacology Authors: Sangh Partap, Mohammad Shahar Yar, Md. Zaheen Hassan, Md. Jawaid Akhtar, Anees A. Siddiqui Tags: Full Paper Source Type: research
Editorial Board: Arch. Pharm. Chem. Life Sci. (9/2017)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - September 1, 2017 Category: Drugs & Pharmacology Tags: Editorial Board Source Type: research
Cover Picture: Arch. Pharm. Chem. Life Sci. (9/2017)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - September 1, 2017 Category: Drugs & Pharmacology Tags: Cover Picture Source Type: research
Delivery of Therapeutic Proteins Using Electrospun Fibers —Recent Developments and Current Challenges
Proteins play a vital role within the human body by regulating various functions and even serving as structural constituent of many body parts. In this context, protein‐based therapeutics have attracted a lot of attention in the last few decades as potential treatment of different diseases. Due to the steadily increasing interest in protein‐based therapeutics, different dosage forms were investigated for delivering such complex macromolecules to the human body. Here, electrospun fibers hold a great potential for embedding proteins without structural damage and for controlled release of the protein for therapeutic appli...
Source: Archiv der Pharmazie - August 28, 2017 Category: Drugs & Pharmacology Authors: Salem Seif, Viktoria Planz, Maike Windbergs Tags: Minireview Source Type: research
