From Lead to Drug Utilizing a Mannich Reaction: The Topotecan Story
Natural products are a rich source of bioactive compounds, and numerous natural compounds have found application in cancer chemotherapy. However, unfavorable physicochemical properties often prevent the use of the original natural product as a drug. A prominent example is camptothecin from the Chinese tree Camptotheca acuminata, which shows extraordinary cytotoxic activity based on a specific molecular mode of action (inhibition of human topoisomerase I). Due to its extremely poor solubility, the original natural product cannot be used as a drug. The marketed drug topotecan was developed from this lead structure by semi‐...
Source: Archiv der Pharmazie - October 31, 2016 Category: Drugs & Pharmacology Authors: Franz Bracher, Tim Tremmel Tags: Review Article Source Type: research
Cover Picture: Arch. Pharm. Chem. Life Sci. (11/2016)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - October 31, 2016 Category: Drugs & Pharmacology Tags: Cover Picture Source Type: research
Recent Advances and Structural Features of Enoyl ‐ACP Reductase Inhibitors of Mycobacterium tuberculosis
Mycobacterium tuberculosis enoyl‐ACP reductase (InhA) has been validated as a promising target for antitubercular agents. Isoniazid (INH), the most prescribed drug to treat tuberculosis (TB), inhibits a NADH‐dependent InhA that provides precursors of mycolic acids, which are components of the mycobacterial cell wall. It is a pro‐drug that needs activation to form the inhibitory INH‐NAD adduct by KatG coding for catalase‐peroxidase. The INH resistance of M. tuberculosis is caused by mutations in KatG, which may lead to multidrug‐resistant TB (MDR‐TB). Hence, there is a need for new drugs that can combat MDR‐...
Source: Archiv der Pharmazie - October 23, 2016 Category: Drugs & Pharmacology Authors: Bharathkumar Inturi, Gurubasavaraj V. Pujar, Madhusudhan N. Purohit Tags: Minireview Source Type: research
Contents: Arch. Pharm. Chem. Life Sci. (10/2016)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - October 3, 2016 Category: Drugs & Pharmacology Tags: Contents Source Type: research
Editorial Board: Arch. Pharm. Chem. Life Sci. (10/2016)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - October 3, 2016 Category: Drugs & Pharmacology Tags: Editorial Board Source Type: research
Cover Picture: Arch. Pharm. Chem. Life Sci. (10/2016)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - October 3, 2016 Category: Drugs & Pharmacology Tags: Cover Picture Source Type: research
Synthesis of New Tricyclic and Tetracyclic Fused Coumarin Sulfonate Derivatives and Their Inhibitory Effects on LPS ‐Induced Nitric Oxide and PGE2 Productions in RAW 264.7 Macrophages: Part 2
The synthesis of a new series of 21 fused coumarin derivatives is described, and the biological evaluation of their in vitro antiinflammatory effects as inhibitors of lipopolysaccharide (LPS)‐induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW 264.7 macrophages. The target compounds 1a–u were first tested for cytotoxicity to determine a non‐toxic concentration for antiinflammatory screening, so that the inhibitory effects against NO and PGE2 production would not be caused by cytotoxicity. Compounds 1f and 1p were the most active PGE2 inhibitors with IC50 values of 0.89 and 0.95 µM, respectively...
Source: Archiv der Pharmazie - September 30, 2016 Category: Drugs & Pharmacology Authors: Mohammed I. El ‐Gamal, Woo‐Seok Lee, Ji‐Sun Shin, Chang‐Hyun Oh, Kyung‐Tae Lee, Jungseung Choi, Nohsun Myoung, Daejin Baek Tags: Full Paper Source Type: research
Design and Synthesis of 4 ‐Anilinothieno[2,3‐d]pyrimidine‐Based Compounds as Dual EGFR/HER‐2 Inhibitors
In this study, new series of 4‐anilinothieno[2,3‐d]pyrimidines were designed, synthesized, and tested as dual EGFR/HER‐2 kinase inhibitors. Five compounds (8a, 8b, 8e–g) demonstrated low to submicromolar inhibition of both kinases with IC50 values of 1.2, 0.6, 0.3, 0.2, 0.4 μM and 8.2, 3.4, 1.3, 0.5, 2.7 μM for the EGFR and HER‐2, respectively. Introduction of a 5,6‐tetramethylene moiety into the thienopyrimidine core bearing a 4‐(3‐fluorobenzyloxy)‐3‐chloroaniline tail resulted in a favorable increase in both the EGFR and HER‐2 inhibitory activities. Compound 8f (IC50 EGFR/HER‐2: 0.2/0.5 μ...
Source: Archiv der Pharmazie - September 30, 2016 Category: Drugs & Pharmacology Authors: Soha R. Abd El Hadi, Deena S. Lasheen, Mahmoud A. Hassan, Khaled A. M. Abouzid Tags: Full Paper Source Type: research
Synthesis, Molecular Mechanism and Pharmacokinetic Studies of New Epoxy Lignan ‐Based Derivatives
The oxidative demethylation procedure for a new epoxy lignan isolated from Piper nigrum was applied to the synthesis of 3’‐methoxy‐3”,4”‐(methylenedioxy)‐2,5‐epoxylignan‐4’‐ol‐6’‐one. This compound inhibited the mRNA expression of the protein patched homolog (Ptch) in human pancreatic cancer cells (PANC1) and therefore might be valuable as a probe for tumor‐related disease. The pharmacokinetic profile of 3'‐methoxy‐3”,4”‐(methylenedioxy)‐2,5‐epoxylignan‐4'‐ol‐6'‐one was rapidly determined using ultra‐fast liquid chromatography. The compound was rapidly absorbed in blood...
Source: Archiv der Pharmazie - September 30, 2016 Category: Drugs & Pharmacology Authors: Yusnita Rifai, Harold B. Tani, Muhammad Nur, Muhammad Aswad, Subehan Lallo, Elly Wahyudin Tags: Full Paper Source Type: research
Synthesis of Some Novel 2 ‐Substitutedbenzyl‐(4)7‐phenyl‐1H‐benzo[d]imidazoles in Mild Conditions as Potent Anti‐Tyrosinase and Antioxidant Agents
Novel 2‐substitutedbenzyl‐4(7)‐phenyl‐1H‐benzo[d]imidazole compounds were synthesized and characterized. Although 2a and 2b were reported previously in the literature, 11 compounds were synthesized (nine of them were newly synthesized) and the tyrosinase inhibitory effects and antioxidant activities of these compounds were studied for the first time. All of the synthesized compounds displayed certain inhibitory effects on tyrosinase, with IC50 values ranging from 37.86 ± 0.24 to 75.81 ± 2.49 μM. Among the compounds, 2j exhibited similar tyrosinase inhibitory effect (IC50 = 37.86 ± 0.24 µM...
Source: Archiv der Pharmazie - August 31, 2016 Category: Drugs & Pharmacology Authors: İnci S. Doğan, Arzu Özel, Zeynep Birinci, Burak Barut, Hasan E. Sellitepe, Bahittin Kahveci Tags: Full Paper Source Type: research
Structural Exploration of Quinazolin ‐4(3H)‐ones as Anticonvulsants: Rational Design, Synthesis, Pharmacological Evaluation, and Molecular Docking Studies
Anticonvulsants effective against multiple seizures are of wide interest as antiepileptic drugs, especially if active against pharmaco‐resistant seizures. Herein, we synthesized 16 different, rationally designed 2‐((6,7‐dimethoxy‐4‐oxo‐2‐phenylquinazolin‐3(4H)‐yl)amino)‐N‐(substituted phenyl)acetamides and screened for anticonvulsant activities through in vivo experiments. Compound 4d emerged as prototype with excellent anti‐seizure action in mice against electroshock, chemically induced and pharmaco‐resistant 6‐Hz seizure models with no symptoms of neurotoxicity and hepatotoxicity (ED50 = 2...
Source: Archiv der Pharmazie - August 31, 2016 Category: Drugs & Pharmacology Authors: Vinod G. Ugale, Sanjay B. Bari Tags: Full Paper Source Type: research
Identification and Characterization of Small ‐Molecule Inhibitors to Selectively Target the DFG‐in over the DFG‐out Conformation of the B‐Raf Kinase V600E Mutant in Colorectal Cancer
V600E is the most common mutation in the B‐Raf kinase domain and the B‐RafV600E mutant has been recognized as an attractive target of colorectal cancer. Here, the structural dynamics of V600E‐induced conformational conversion in the B‐Raf activation loop (A‐loop) was characterized in detail using a computational simulation strategy. The simulations revealed that the V600E mutation would induce A‐loop flipping from DFG‐out to DFG‐in, and the approved B‐Raf inhibitor vemurafenib exhibits strong selectivity for the mutant over the wild‐type kinase. The selectivity is closely associated with the kinase conf...
Source: Archiv der Pharmazie - August 31, 2016 Category: Drugs & Pharmacology Authors: Huixiang Yao, Qun Sun, Jinshui Zhu Tags: Full Paper Source Type: research
Synthesis, Cyclooxygenase Inhibition, Anti ‐Inflammatory Evaluation, and Ulcerogenic Liability of New 1,3,5‐Triarylpyrazoline Derivatives Possessing a Methanesulfonyl Pharmacophore
A new series of 1,3,5‐triarylpyrazolines 13a–l was synthesized and all prepared compounds were evaluated for their in vitro COX‐1/COX‐2 inhibitory activity and in vivo anti‐inflammatory activity. All test compounds were more selective for the COX‐2 isozyme and showed good in vivo anti‐inflammatory activity. Compound 13h was the most COX‐2 selective compound (COX‐2 selectivity index (SI) = 10.23) and the most potent anti‐inflammatory derivative (ED50 = 60.1 µmol/kg) in comparison with celecoxib (COX‐2 SI = 9.29 and ED50 = 81.4 µmol/kg). All screened compounds were less ulcerogenic...
Source: Archiv der Pharmazie - August 31, 2016 Category: Drugs & Pharmacology Authors: Khaled R. A. Abdellatif, Wael A. A. Fadaly, Amany A. Azouz Tags: Full Paper Source Type: research
Contents: Arch. Pharm. Chem. Life Sci. (9/2016)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - August 31, 2016 Category: Drugs & Pharmacology Tags: Contents Source Type: research
Editorial Board: Arch. Pharm. Chem. Life Sci. (9/2016)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - August 31, 2016 Category: Drugs & Pharmacology Tags: Editorial Board Source Type: research
