PMID- 37464836
OWN - NLM
STAT- Publisher
LR  - 20231024
IS  - 1875-6638 (Electronic)
IS  - 1573-4064 (Linking)
VI  - 19
IP  - 10
DP  - 2023
TI  - Development of Dual Inhibitors of Soluble Epoxide Hydrolase/Fatty Acid Amide 
      Hydrolase with Tetrazole Core.
PG  - 1037-1048
LID - 10.2174/1573406419666230718152453 [doi]
AB  - INTRODUCTION: The attractive biological actions of the eicosatrienoic acids 
      (EETs) and endocannabinoids (eCBs) are terminated by means of enzymatic 
      hydrolysis via soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase 
      (FAAH) enzymes. Simultaneous inhibition of both enzymes is considered a novel 
      approach in the treatment of inflammatory and neuropathic pain. METHODS: In this 
      study, a novel series of tetrazole derivatives as dual sEH/FAAH inhibitors were 
      designed, synthesized, and biologically evaluated. Compounds 6c, 7d, and 8a, the 
      most potent inhibitors against FAAH and sEH enzymes with acceptable IC(50) 
      values, significantly decreased carrageenan- induced paw edema 5h after 
      carrageenan injection compared to the control group compound. In addition, 
      compound 7d exhibited a significant reduction in pain scores compared to the 
      control group. RESULTS: Docking studies showed that the presented dual inhibitors 
      could bind to the essential residues in the catalytic sites of both enzymes. In 
      silico prediction of several pharmacokinetic properties suggests that these dual 
      inhibitors could potentially be orally active agents. CONCLUSION: These 
      structures will be a valuable scaffold to develop soluble epoxide hydrolase 
      inhibitors with dual potency towards fatty acid amide hydrolase.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Mehrandish, Sara
AU  - Mehrandish S
AD  - Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti 
      University of Medical Sciences, Tehran, Iran.
FAU - Rezaee, Elham
AU  - Rezaee E
AD  - Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti 
      University of Medical Sciences, Tehran, Iran.
FAU - Sedaghat, Anna
AU  - Sedaghat A
AD  - Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti 
      University of Medical Sciences, Tehran, Iran.
FAU - Heidarli, Elmira
AU  - Heidarli E
AD  - Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti 
      University of Medical Sciences, Tehran, Iran.
FAU - Naderi, Nima
AU  - Naderi N
AD  - Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti 
      University of Medical Sciences, Tehran, Iran.
FAU - Tabatabai, Sayyed Abbas
AU  - Tabatabai SA
AD  - Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti 
      University of Medical Sciences, Tehran, Iran.
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Med Chem
JT  - Medicinal chemistry (Shariqah (United Arab Emirates))
JID - 101240303
SB  - IM
OTO - NOTNLM
OT  - Synthesis
OT  - fatty acid amide hydrolase
OT  - inflammatory
OT  - pain
OT  - soluble epoxide hydrolase
OT  - tetrazole
EDAT- 2023/07/19 06:43
MHDA- 2023/07/19 06:43
CRDT- 2023/07/19 03:44
PHST- 2022/12/12 00:00 [received]
PHST- 2023/05/10 00:00 [revised]
PHST- 2023/05/31 00:00 [accepted]
PHST- 2023/07/19 06:43 [pubmed]
PHST- 2023/07/19 06:43 [medline]
PHST- 2023/07/19 03:44 [entrez]
AID - MC-EPUB-132989 [pii]
AID - 10.2174/1573406419666230718152453 [doi]
PST - ppublish
SO  - Med Chem. 2023;19(10):1037-1048. doi: 10.2174/1573406419666230718152453.