33407-50-0Relevant academic research and scientific papers
Discovery of novel peptidomimetics as irreversible CHIKV NsP2 protease inhibitors using quantum mechanical-based ligand descriptors
El-Labbad, Eman M.,Ismail, Mohammed A. H.,Abou Ei Ella, Dalal A.,Ahmed, Marawan,Wang, Feng,Barakat, Khaled H.,Abouzid, Khaled A. M.
, p. 1518 - 1527 (2015)
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus. Recent outbreaks of CHIKV infections have been reported in Asia, Africa, and Europe. The symptoms of CHIKV infection include fever, headache, nausea, vomiting, myalgia, rash, and chronic persistent arthralgia. To date, no vaccines or selective antiviral drugs against this important emerging virus have been reported. In this study, the design, synthesis, and antiviral activity screening of new topographical peptidomimetics revealed three potential prototype agents 3a, 4b, and 5d showing 93-100% maximum inhibition of CHIKV replication in cell-based assay having EC90 of 8.76-9.57 μg/mL. Intensive molecular modeling studies including covalent docking, lowest unoccupied molecular orbital energies, and the atomic condensed Fukui functions calculations strongly suggested the covalent binding of peptidomimetics 3a, 4b, and 5d to CHIKV nsP2 protease leading to permanent enzyme inactivation via Michael adduct formation between α/β-unsaturated ketone functionality in our designed peptidomimetics and active site catalytic cysteine1013. Furthermore, small molecular weight peptidomimetics 3a and 4b satisfied the Lipinski rule of five for drug-likeness and showed promising intestinal absorption and aqueous solubility via computational admet studies making them promising hits for further optimization. Covalent docking of the inhibitor 3a with the nsP2 enzyme showing the proposed Michael adduct formed between inhibitors 3a and the side chain of catalytic Cysteine1013.
5-Oxo-ETE receptor antagonists
Gore, Vivek,Patel, Pranav,Chang, Chih-Tsung,Sivendran, Sashikala,Kang, Namin,Ouedraogo, Yannick P.,Gravel, Sylvie,Powell, William S.,Rokach, Joshua
, p. 3725 - 3732 (2013/06/27)
5-Oxo-ETE is the most powerful eosinophil chemoattractant among lipid mediators. Eosinophil infiltration into the lungs of asthmatics may be responsible for the late phase of inflammatory asthma. We have designed and synthesized a 5-oxo-ETE receptor antagonist, the purpose of which is to prevent eosinophil migration to the lung during an asthma attack and thereby reduce asthma symptoms.
