In:
ChemistrySelect, Wiley, Vol. 3, No. 37 ( 2018-10-09), p. 10305-10310
Abstract:
The oxadiazole linked benzoxazoles derivatives were designed using scaffold hopping approach and their molecular level interactions with both isoforms of cyclooxygenases, C yclo OX ygenase‐1 ( COX‐1 ) and C yclo OX ygenase‐2 ( COX‐2 ), were carried out using docking protocols. Mini library of oxadiazole linked benzoxazoles derivatives were synthesized and tested for their COX inhibitory activity by in vitro enzyme assay. The results indicated that compound 2‐(((5‐(2,4‐dichlorophenyl)‐1,2,4‐oxadiazol‐3‐yl)methyl)thio)benzo[d]oxazole (5 h) , 2‐(((5‐(4‐nitrophenyl)‐1,2,4‐oxadiazol‐3‐yl)methyl)thio)benzo[d]oxazole (5 j) and 2‐(((5‐(4‐(trifluoromethyl)phenyl)‐1,2,4‐oxadiazol‐3‐yl)methyl)thio)benzo[d]oxazole (5 k) selectively inhibited COX‐2 enzyme. The compound 5 j exhibited strong selective COX‐2 inhibition (IC 50 =4.83 μM) followed by compound 5 h (IC 50 =5.10 μM) and 5 k (IC 50 =6.70 μM). The in vivo anti‐inflammatory activity of compound 5 j was found to have better efficiency than the standard drug Ibuprofen at both 3 h and 5 h intervals. The significant molecular level interactions with respect to position of benzoxazole, 1,2,4‐oxadiazole and substituted aryl groups in both COX‐1 and COX‐2 active sites were discussed. Subsequently, 2,2‐diphenyl‐2‐picrylhydrazyl (DPPH) anti‐oxidant activity was also checked for all the compounds and the compound 5 j was found to be good anti‐oxidant among the series with an IC 50 of 34.5 μM.
Type of Medium:
Online Resource
ISSN:
2365-6549
,
2365-6549
DOI:
10.1002/slct.201801558
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2844262-3
