synthetic analogs
Recently Published Documents


TOTAL DOCUMENTS

491
(FIVE YEARS 46)

H-INDEX

52
(FIVE YEARS 3)

2021 ◽  
Author(s):  
Elany Barbosa Da Silva ◽  
Vandna Sharma ◽  
Lilian Hernandez-Alvarez ◽  
Arthur H Tang ◽  
Alexander Stoye ◽  
...  

Gallinamide A, a metabolite of the marine cyanobacterium Schizothrix sp., selectively inhibits cathepsin L-like cysteine proteases. We evaluated potency of gallinamide A and 23 synthetic analogs against intracellular Trypanosoma cruzi amastigotes and the cysteine protease, cruzain. We determined the co-crystal structures of cruzain with gallinamide A and two synthetic analogs at ~2Å. SAR data revealed that the N-terminal end of gallinamide A is loosely bound and weakly contributes in drug-target interactions. At the C-terminus, the intramolecular π-π stacking interactions between the aromatic substituents at P1 ′ and P1 restrict the bioactive conformation of the inhibitors, thus minimizing the entropic loss associated with target binding. Molecular dynamics simulations showed that in the absence of an aromatic group at P1, the substituent at P1′ interacts with tryptophan-184. The P1-P1′ interactions had no effect on anti-cruzain activity whereas anti-T. cruzi potency increased by ~5-fold, likely due to an increase in solubility/permeability of the analogs.


Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1535
Author(s):  
Macarena Funes Chabán ◽  
Martina Hrast ◽  
Rok Frlan ◽  
Dafni G. Graikioti ◽  
Constantinos M. Athanassopoulos ◽  
...  

Enzymes MurA and MurF, involved in bacterial cell wall synthesis, have been validated as targets for the discovery of novel antibiotics. A panel of plant-origin antibacterial diterpenes and synthetic analogs derived therefrom were investigated for their inhibitory properties on these enzymes from Escherichia coli and Staphylococcus aureus. Six compounds were proven to be effective for inhibiting MurA from both bacteria, with IC50 values ranging from 1.1 to 25.1 µM. To further mechanistically investigate the nature of binding and to explain the activity, these compounds were docked into the active site of MurA from E. coli. The aromatic ring of the active compounds showed a T-shaped π–π interaction with the phenyl ring of Phe328, and at least one hydrogen bond was formed between the hydroxy groups and Arg120 and/or Arg91. The results disclosed here establish new chemical scaffolds for the development of novel entities targeting MurA as potential antibiotics to combat the threat of pathogenic bacteria, particularly resistant strains.


Author(s):  
Ayyoub Selka ◽  
Fanta J. Ndongou Moutombi ◽  
Jacques Jean-François ◽  
Mohamed Touaibia

: The hydroxycinnamic acid scaffold is extremely versatile with various biological activities. This review will highlight the progress of the biological activities of hydroxycinnamic acids and their related synthetic analogs, including recently reported anti-cancer, anti-inflammatory, and antioxidant activities.


2021 ◽  
Vol 116 ◽  
pp. 105319
Author(s):  
Wenliang Wang ◽  
Denghui Gao ◽  
Qiancheng Zheng ◽  
Xi Zhao ◽  
Risong Na ◽  
...  

ChemMedChem ◽  
2021 ◽  
Author(s):  
Yolanda Kleiner ◽  
Christoph Pöverlein ◽  
Jannike Klädtke ◽  
Michael Kurz ◽  
Henrik F. König ◽  
...  

2021 ◽  
Author(s):  
Siham Memdouh ◽  
Ivana Gavrilović ◽  
Kelsey Ng ◽  
David Cowan ◽  
Vincenzo Abbate

2021 ◽  
Author(s):  
Morlok Andreas ◽  
Bernard Charlier ◽  
Christian Renggli ◽  
Stephan Klemme ◽  
Olivier Namur ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document