Use of the Monte Carlo Method for OECD Principles ‐Guided QSAR Modeling of SIRT1 Inhibitors
SIRT1 inhibitors offer therapeutic potential for the treatment of a number of diseases including cancer and human immunodeficiency virus infection. A diverse series of 45 compounds with reported SIRT1 inhibitory activity has been employed for the development of quantitative structure–activity relationship (QSAR) models using the Monte Carlo optimization method. This method makes use of simplified molecular input line entry system notation of the molecular structure. The QSAR models were built up according to OECD principles. Three subsets of three splits were examined and validated by respective external sets. All the th...
Source: Archiv der Pharmazie - November 30, 2016 Category: Drugs & Pharmacology Authors: Ashwani Kumar, Shilpi Chauhan Tags: Full Paper Source Type: research
Synthesis and Evaluation of New Naphthalene and Naphthoquinone Derivatives as Anticancer Agents
DNA topoisomerase I inhibitors, both synthetic and of natural origin, are receiving increasing consideration primarily as drugs against refractory tumors. Alkannin and shikonin, two enantiomeric dyes from Alkanna tinctoria and Lithospermum erythrorhizon, have been known over many centuries as dyestuff, wound healing, anti‐inflammatory, antibacterial and antitumor substances. Although multiple mechanisms appear to be implicated, their potency is associated with the inhibition of topoisomerase I and with the redox properties of the naphthazarin scaffold. Here, the synthesis of new naphthalene and naphthoquinone derivatives...
Source: Archiv der Pharmazie - November 30, 2016 Category: Drugs & Pharmacology Authors: Giovanni L. Beretta, Giovanni Ribaudo, Ileana Menegazzo, Rosanna Supino, Giovanni Capranico, Franco Zunino, Giuseppe Zagotto Tags: Full Paper Source Type: research
Synthesis and Docking of Novel 3 ‐Indolylpropyl Derivatives as New Polypharmacological Agents Displaying Affinity for 5‐HT1AR/SERT
A series of novel 3‐indolylpropyl derivatives was synthesized and evaluated for their binding affinities at the serotonin‐1A receptor subtype (5‐HT1AR) and the 5‐HT transporter (SERT). Compounds 11b and 14b exhibited the highest affinities at the 5‐HT1AR (Ki = 43 and 56 nM), whereas compounds 11c and 14a were the most potent analogs at the SERT (Ki = 34 and 17 nM). On the other hand, compounds 14b and 11d showed potent activity at both targets, displaying a profile that makes them promising leads for the search for novel potent ligands with a dual mechanism of action. Molecular docking studies in all ...
Source: Archiv der Pharmazie - November 30, 2016 Category: Drugs & Pharmacology Authors: Hern án Pessoa‐Mahana, Paul Silva‐Matus, C. David Pessoa‐Mahana, Hery Chung, Patricio Iturriaga‐Vásquez, Gabriel Quiroz, Patricia Möller‐Acuña, Gerald Zapata‐Torres, Claudio Saitz‐Barría, Ramiro Araya‐Maturana, Miguel Reyes‐Parada Tags: Full Paper Source Type: research
Fragment ‐Based Design, Synthesis, and Biological Evaluation of 1‐Substituted‐indole‐2‐carboxylic Acids as Selective Mcl‐1 Inhibitors
Based on a known selective Mcl‐1 inhibitor, 6‐chloro‐3‐(3‐(4‐chloro‐3,5‐dimethylphenoxy)propyl)‐1H‐indole‐2‐carboxylic acid, we applied a fragment‐based approach to obtain new molecules that extended into the p1 pocket of the BH3 groove and then exhibited binding selectivity for the Mcl‐1 over the Bcl‐2 protein. After we deconstructed the 1H‐indole‐2‐carboxylic acid from the parental molecule, a benzenesulfonyl was substituted at the 1‐position to adopt a geometry preferred for accessing the p1 pocket according to the binding mode of the parental molecule identified by X‐ray crystall...
Source: Archiv der Pharmazie - November 30, 2016 Category: Drugs & Pharmacology Authors: Ziqian Wang, Wenjie Xu, Ting Song, Zongwei Guo, Lu Liu, Yudan Fan, Anhui Wang, Zhichao Zhang Tags: Full Paper Source Type: research
Identification of 8 ‐Hydroxyquinoline Derivatives Active Against Somatic V658F Mutant JAK1‐Dependent Cells
We present the results of an extensive virtual screening campaign based on a multi‐step screening protocol involving ligand docking. The screening yielded five new, experimentally validated inhibitors of JAK1 with 8‐hydroxyquinoline as a novel hinge‐binding scaffold. The compounds did not only display favorable potencies in a JAK1V658F‐driven cell‐based assay but were also shown to be non‐cytotoxic on rat liver cells.
An extensive virtual screening campaign was carried out, resulting in multiple novel JAK1 inhibitors with the 8‐hydroxyquinoline scaffold as the hinge‐binding motif. The compounds have been s...
Source: Archiv der Pharmazie - November 9, 2016 Category: Drugs & Pharmacology Authors: R óbert Kiss, Dávid Bajusz, Rebekah Baskin, Katalin Tóth, Katalin Monostory, Peter P. Sayeski, György M. Keserű Tags: Full Paper Source Type: research
Contents: Arch. Pharm. Chem. Life Sci. (11/2016)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - November 1, 2016 Category: Drugs & Pharmacology Tags: Contents Source Type: research
Editorial Board: Arch. Pharm. Chem. Life Sci. (11/2016)
(Source: Archiv der Pharmazie)
Source: Archiv der Pharmazie - November 1, 2016 Category: Drugs & Pharmacology Tags: Editorial Board Source Type: research
Prenylated Xanthones from the Roots of Cudrania tricuspidata as Inhibitors of Lipopolysaccharide ‐Stimulated Nitric Oxide Production
Investigation of the CH2Cl2 and EtOAc‐soluble fractions of the roots of Cudrania tricuspidata afforded 31 compounds. The structures of the isolated compounds were determined on the basis of spectroscopic data interpretation such as 1D and 2D NMR analysis and elucidated as xanthones with prenyl moieties including four simple xanthones (1–4), five prenylated xanthones with one prenyl moiety (5–7, 20, and 21), and 22 prenylated xanthones with two prenyl moieties (8–19 and 22–31). Among them, three diprenylated xanthones named cudracuspixanthones E–G (16, 29, and 31) were first isolated in nature. Xanthones 2, 5, 6...
Source: Archiv der Pharmazie - October 31, 2016 Category: Drugs & Pharmacology Authors: Yang Hee Jo, Seon Beom Kim, Qing Liu, Bang Yeon Hwang, Mi Kyeong Lee Tags: Full Paper Source Type: research
Drotaverine – a Concealed Cytostatic!
Drotaverine (also known as dihydroperparine or No‐Spa®) is an antispasmodic drug closely related to papaverin. Drotaverin also acts as a cytostatic compound for several human tumor cell lines and nonmalignant mouse fibroblasts, and EC50 values as low as 3.0 μM were observed in SRB assays for HT‐29 human colorectal carcinoma cells. Small structural changes (e.g., aromatization, benzylic oxidation) led to a reduced activity or a complete loss of cytotoxicity. Staining of the cells with acridine orange showed the cell membrane of the dead cells to be still intact, and a slight G1/G0 arrest in the treated cells was obs...
Source: Archiv der Pharmazie - October 31, 2016 Category: Drugs & Pharmacology Authors: Ioana Z. Pavel, Lucie Heller, Sven Sommerwerk, Anne Loesche, Ahmed Al ‐Harrasi, René Csuk Tags: Full Paper Source Type: research
Aminoalkyl Derivatives of 8 ‐Alkoxypurine‐2,6‐diones: Multifunctional 5‐HT1A/5‐HT7 Receptor Ligands and PDE Inhibitors with Antidepressant Activity
In the search for potential psychotropic agents, a new series of 3,7‐dimethyl‐ and 1,3‐dimethyl‐8‐alkoxypurine‐2,6‐dione derivatives of arylpiperazines, perhydroisoquinolines, or tetrahydroisoquinolines with flexible alkylene spacers (5–16 and 21–32) were synthesized and evaluated for 5‐HT1A/5‐HT7 receptor affinities as well as PDE4B1 and PDE10A inhibitory properties. The 1‐(4‐(4‐(2‐hydroxyphenyl)piperazin‐1‐yl)butyl)‐3,7‐dimethyl‐8‐propoxypurine‐2,6‐dione (16) and 7‐(2‐hydroxyphenyl)piperazinylalkyl‐1,3‐dimethyl‐8‐ethoxypurine‐2,6‐diones (31 and 32) as potent d...
Source: Archiv der Pharmazie - October 31, 2016 Category: Drugs & Pharmacology Authors: Gra żyna Chłoń‐Rzepa, Agnieszka Zagórska, Paweł Żmudzki, Adam Bucki, Marcin Kołaczkowski, Anna Partyka, Anna Wesołowska, Grzegorz Kazek, Monika Głuch‐Lutwin, Agata Siwek, Gabriela Starowicz, Maciej Pawłowski Tags: Full Paper Source Type: research
Synthesis and Carbonic Anhydrase Inhibition of Novel 2 ‐(4‐(Aryl)thiazole‐2‐yl)‐3a,4,7,7a‐tetrahydro‐1H‐4,7‐methanoisoindole‐1,3(2H)‐dione Derivatives
In this study, a number of novel 2‐(4‐(aryl)thiazole‐2‐yl)‐3a,4,7,7a‐tetrahydro‐1H‐4,7‐methanoisoindole‐1,3(2H)‐dione derivatives were synthesized and evaluated for their inhibitory characteristics against the human CA isoenzymes I and II (hCA I and hCA II). The structures of the new molecules 8a–i were confirmed by means of IR, 1H NMR, 13C NMR, and elemental analysis. These compounds exhibited excellent inhibitory effects, in the low nanomolar range, with Ki values in the range of 27.07–37.80 nM against hCA I and in the range of 11.80–25.81 nM against hCA II. Our findings suggest that the n...
Source: Archiv der Pharmazie - October 31, 2016 Category: Drugs & Pharmacology Authors: Umit M. Kocyigit, Osman Nuri Aslan, Ilhami Gulcin, Yusuf Temel, Mustafa Ceylan Tags: Full Paper Source Type: research
Bacterial Peptide Deformylase Inhibition of Tetrazole ‐Substituted Biaryl Acid Analogs: Synthesis, Biological Evaluations, and Molecular Docking Study
The synthesis and screening of tetrazole‐substituted biaryl acid analogs 7a–l as bacterial peptide deformylase (PDF) enzyme inhibitors is reported. The compounds 7e (IC50 value = 5.50 μM) and 7g (IC50 value = 7.25 μM) showed good PDF inhibition activity. The compounds 7e (MIC range = 10.75–11.66 μg/mL) and 7g (MIC range = 8.91–12.83 μg/mL) also showed potent antibacterial activity when compared with the standard ciprofloxacin (MIC range = 25–50 μg/mL). Thus, the active derivatives were not only potent PDF enzyme inhibitors but also efficient antibacterial agents. In order to gai...
Source: Archiv der Pharmazie - October 31, 2016 Category: Drugs & Pharmacology Authors: Firoz A. Kalam Khan, Rajendra H. Patil, Manjiri Patil, Rohidas Arote, Devanand B. Shinde, Jaiprakash N. Sangshetti Tags: Full Paper Source Type: research
Antioxidant Activity, Acetylcholinesterase, and Carbonic Anhydrase Inhibitory Properties of Novel Ureas Derived from Phenethylamines
A series of ureas derived from phenethylamines were synthesized and evaluated for human carbonic anhydrase (hCA) I and II, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzyme inhibitory activities and antioxidant properties. The ureas were synthesized from the reactions of substituted phenethylamines with N,N‐dimethylcarbamoyl chloride; then, the synthesized compounds were converted to their corresponding phenolic derivatives via O‐demethylation. hCA I and II were effectively inhibited by the newly synthesized compounds, with Ki values in the range of 0.307–0.432 nM for hCA I and 0.149–0.278 nM...
Source: Archiv der Pharmazie - October 31, 2016 Category: Drugs & Pharmacology Authors: Kadir Aksu, B ünyamin Özgeriş, Parham Taslimi, Ali Naderi, İlhami Gülçin, Süleyman Göksu Tags: Full Paper Source Type: research
Synthesis and Biological Evaluation of Novel Indomethacin Derivatives as Potential Anti ‐Colon Cancer Agents
The molecular structure of indomethacin was used as a starting scaffold for the synthesis of 20 novel analogs and to study their effects on the proliferation of three human colon cancer cell lines, HCT‐116, HT‐29, and Caco‐2, by MTT assay. The synthesized indomethacin analogs were characterized on the basis of IR, 1H NMR, 13C NMR, mass spectral data, and elemental analysis results. Cytotoxicity assay results showed that the indomethacin amide analog 2 was the most potent anticancer agent (IC50 = 0.78, 0.09, and 0.0127 μg/mL) against the three colon cancer cell lines, respectively, being more potent than the st...
Source: Archiv der Pharmazie - October 31, 2016 Category: Drugs & Pharmacology Authors: Amel Mostafa Farrag Tags: Full Paper Source Type: research
Novel Tacrine ‐Based Pyrano[3’,4’:5,6]pyrano[2,3‐b]quinolinones: Synthesis and Cholinesterase Inhibitory Activity
In order to develop effective anti‐cholinesterase compounds, a novel series of pyrano[3’,4’:5,6]pyrano[2,3‐b]quinolinones were designed, synthesized, and evaluated in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). All derivatives showed very good AChE inhibitory (AChEI) activity (IC50 = 0.37–5.62 μM) compared with rivastigmine (IC50 = 11.07 μM). Among them, 11‐amino‐12‐(2,3‐dichlorophenyl)‐3‐methyl‐7,8,9,10‐tetrahydropyrano[3’,4’:5,6]pyrano[2,3‐b]quinolin‐1(12H)‐one (6f) displayed the best inhibitory activity. However, most of the synthesized co...
Source: Archiv der Pharmazie - October 31, 2016 Category: Drugs & Pharmacology Authors: Roshanak Hariri, Zahra Afshar, Mohammad Mahdavi, Maliheh Safavi, Mina Saeedi, Zahra Najafi, Reyhaneh Sabourian, Elahe Karimpour ‐Razkenari, Najmeh Edraki, Farshad Homayouni Moghadam, Abbas Shafiee, Mahnaz Khanavi, Tahmineh Akbarzadeh Tags: Full Paper Source Type: research
