PMID- 29732612
OWN - NLM
STAT- MEDLINE
DCOM- 20181003
LR  - 20181004
IS  - 1521-4184 (Electronic)
IS  - 0365-6233 (Linking)
VI  - 351
IP  - 6
DP  - 2018 Jun
TI  - Synthesis of substituted fluorobenzimidazoles as inhibitors of 5-lipoxygenase and 
      soluble epoxide hydrolase for anti-inflammatory activity.
PG  - e1800030
LID - 10.1002/ardp.201800030 [doi]
AB  - A new series of 
      4-((5-fluoro-6-(substituted)-1H-benzo[d]imidazol-2-ylthio)methyl)-benzoic acids 
      4a-o and 
      2-(5-fluoro-6-(substituted)-1H-benzo[d]imidazol-2-ylthio)-2-methylpropanoic acids 
      8a-e were synthesized, and their inhibitory potencies against soluble epoxide 
      hydrolase (sEH) and 5-lipoxygenase (5-LOX) were investigated. These molecules 
      were designed based on the combination of 5-LOX and sEH pharmacophores, resulting 
      in hybrid analogs with potent sEH and 5-LOX inhibitory activity. Compound 4g 
      showed remarkable activity with IC(50) values of less than 1 muM (0.9 muM) against 
      5-LOX, while compound 4k displayed promising activity against sEH with IC(50) 
       </= 1 muM (0.7 muM). These compounds were evaluated for their in vivo potential 
      using the carrageenan-induced rat paw edema assay. Based on the obtained results, 
      the structure-activity relationship was established and a correlation between the 
      activities was observed. Compounds 4f, 4g, 4k, 4n, and 8e showed potent 
      anti-inflammatory activity and significant inhibition of edema (64.13, 67.39, 
      66.30, 65.21, and 58.69%, respectively) at a dose of 100 mg/kg, comparable to the 
      standard drug ibuprofen (70.65%) at 3 h.
CI  - (c) 2018 Deutsche Pharmazeutische Gesellschaft.
FAU - Nandha, B
AU  - Nandha B
AUID- ORCID: 0000-0002-5825-8747
AD  - Department of Pharmaceutical Chemistry, Vivekananda College of Pharmacy, Rajiv 
      Gandhi University of Health Sciences, Bangalore, India.
FAU - Ramareddy, Sureshbabu A
AU  - Ramareddy SA
AD  - Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, 
      Bangalore, India.
FAU - Kuntal, Hazra
AU  - Kuntal H
AUID- ORCID: 0000-0003-0364-9211
AD  - Department of Pharmaceutical Chemistry, Bharat Technology, Howrah, Banitabla, 
      India.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20180507
PL  - Germany
TA  - Arch Pharm (Weinheim)
JT  - Archiv der Pharmazie
JID - 0330167
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Benzimidazoles)
RN  - 0 (Lipoxygenase Inhibitors)
RN  - 9000-07-1 (Carrageenan)
RN  - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - WK2XYI10QM (Ibuprofen)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/chemical synthesis/chemistry/*pharmacology
MH  - Arachidonate 5-Lipoxygenase/drug effects
MH  - Benzimidazoles/chemical synthesis/chemistry/*pharmacology
MH  - Carrageenan
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Edema/*drug therapy/enzymology
MH  - Epoxide Hydrolases/antagonists & inhibitors
MH  - Female
MH  - Humans
MH  - Ibuprofen/pharmacology
MH  - Inflammation/*drug therapy/enzymology
MH  - Inhibitory Concentration 50
MH  - Lipoxygenase Inhibitors/chemical synthesis/chemistry/pharmacology
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - 5-lipoxygenase
OT  - anti-inflammatory activity
OT  - fluorobenzimidazole
OT  - rat paw edema
OT  - soluble epoxide hydrolase
EDAT- 2018/05/08 06:00
MHDA- 2018/10/04 06:00
CRDT- 2018/05/08 06:00
PHST- 2018/02/14 00:00 [received]
PHST- 2018/04/08 00:00 [revised]
PHST- 2018/04/11 00:00 [accepted]
PHST- 2018/05/08 06:00 [pubmed]
PHST- 2018/10/04 06:00 [medline]
PHST- 2018/05/08 06:00 [entrez]
AID - 10.1002/ardp.201800030 [doi]
PST - ppublish
SO  - Arch Pharm (Weinheim). 2018 Jun;351(6):e1800030. doi: 10.1002/ardp.201800030. 
      Epub 2018 May 7.