Kato, Eisuke Kawakami, Kazuhiro Kawabata, Jun
Published in
Journal of enzyme inhibition and medicinal chemistry
Dipeptidyl peptidase 4 (DPP-4) inhibitors are used for the treatment of type-2 diabetes mellitus. Various synthetic inhibitors have been developed to date, and plants containing natural DPP-4 inhibitors have also been identified. Here, 13 plant samples were tested for their DPP-4 inhibitory activity. Macrocarpals A-C were isolated from Eucalyptus g...
Pessôa, Marco T C Alves, Silmara L G Taranto, Alex G Villar, José A F P Blanco, Gustavo Barbosa, Leandro A
Published in
Journal of enzyme inhibition and medicinal chemistry
Digoxin and other cardiotonic steroids (CTS) exert their effect by inhibiting Na,K-ATPase (NKA) activity. CTS bind to the various NKA isoforms that are expressed in different cell types, which gives CTS their narrow therapeutic index. We have synthesised a series of digoxin derivatives (γ-Benzylidene digoxin derivatives) with substitutions in the l...
Vermelho, Alane Beatriz da Silva Cardoso, Verônica Ricci Junior, Eduardo Dos Santos, Elisabete Pereira Supuran, Claudiu T
Published in
Journal of enzyme inhibition and medicinal chemistry
Sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors targeting the α-class enzyme from the protozoan pathogen Trypanosoma cruzi, responsible of Chagas disease, were recently reported. Although many such derivatives showed low nanomolar activity in vitro, they were inefficient anti-T. cruzi agents in vivo. Here, we show that by formulating suc...
Kurup, Sonali McAllister, Bradley Liskova, Pavlina Mistry, Trusha Fanizza, Anthony Stanford, Dan Slawska, Jolanta Keller, Ulrich Hoellein, Alexander
Published in
Journal of enzyme inhibition and medicinal chemistry
Simultaneous inhibition of multiple kinases has been suggested to provide synergistic effects on inhibition of tumour growth and resistance. This study describes the design, synthesis and evaluation of 18 compounds incorporating a pyrrolo[2,3-d]pyrimidine scaffold for dual inhibition of epidermal growth factor receptor kinase (EGFR) and aurora kina...
De Vita, Daniela Angeli, Andrea Pandolfi, Fabiana Bortolami, Martina Costi, Roberta Di Santo, Roberto Suffredini, Elisabetta Ceruso, Mariangela Del Prete, Sonia Capasso, Clemente
...
Published in
Journal of enzyme inhibition and medicinal chemistry
We discovered novel and selective sulfonamides/amides acting as inhibitors of the α-carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic bacterium Vibrio cholerae (VchCA). This Gram-negative bacterium is the causative agent of cholera and colonises the upper small intestine where sodium bicarbonate is present at a high concentration. The seconda...
Ma, Lingman Zhang, Zhen Xue, Xiaowen Wan, Yumeng Ye, Boping Lin, Kejiang
Published in
Journal of enzyme inhibition and medicinal chemistry
Fibrotic diseases have become a major cause of death in the developed world. AdipoR1 agonists are potent inhibitors of fibrotic responses. Here, we focused on the in silico identification of novel AdipoR1 peptide agonists. A homology model was constructed to predict the 3D structure of AdipoR1. By docking to known active peptides, the putative acti...
Lu, Xiaoyun Zhang, Zhang Ren, Xiaomei Wang, Deping Ding, Ke
Published in
Journal of enzyme inhibition and medicinal chemistry
Bcr-AblT315I induced drug resistance remains a major challenge to chronic myelogenous leukemia (CML) treatment. Herein, we reported GZD856 as a novel orally bioavailable Bcr-AblT315I inhibitor, which strongly suppressed the kinase activities of both native Bcr-Abl and the T315I mutant with IC50 values of 19.9 and 15.4 nM, and potently inhibited pro...
Stanica, Luciana Gheorghiu, Mihaela Stan, Miruna Polonschii, Cristina David, Sorin Bratu, Dumitru Dinischiotu, Anca Supuran, Claudiu T Gheorghiu, Eugen
Published in
Journal of enzyme inhibition and medicinal chemistry
Carbonic anhydrase IX (CA IX) is an important orchestrator of hypoxic tumour environment, associated with tumour progression, high incidence of metastasis and poor response to therapy. Due to its tumour specificity and involvement in associated pathological processes: tumourigenesis, angiogenesis, inhibiting CA IX enzymatic activity has become a va...
Burmaoğlu, Serdar Seçinti, Hatice Mozioğlu, Erkan Gören, Ahmet C Altundaş, Ramazan Seçen, Hasan
Published in
Journal of enzyme inhibition and medicinal chemistry
Four multicaulin and miltirone-like phenanthrene derivatives were synthesised and evaluated as antituberculosis agents. The crucial step of the synthesis was Pschorr coupling of 4-(3-isopropyl-4-methoxyphenyl)-2-(2-aminophenyl)ethane (13) to give 2-isopropyl-3-methoxy-9,10-dihydrophenanthrene (9) and 4-isopropyl-3-methoxy-9,10-dihydrophenanthrene (...
Abdoli, Morteza Angeli, Andrea Bozdag, Murat Carta, Fabrizio Kakanejadifard, Ali Saeidian, Hamid Supuran, Claudiu T
Published in
Journal of enzyme inhibition and medicinal chemistry
A series of benzo[d]thiazole-5- and 6-sulfonamides has been synthesized and investigated for the inhibition of several human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms, using ethoxzolamide (EZA) as lead molecule. 2-Amino-substituted, 2-acylamino- and halogenated (bromo-and iodo-derivatives at the heterocyclic ring) compounds led to several in...
