PMID- 31718011
OWN - NLM
STAT- MEDLINE
DCOM- 20200331
LR  - 20200331
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 20
IP  - 22
DP  - 2019 Nov 11
TI  - Anti-Inflammatory and Anti-Hyperuricemic Functions of Two Synthetic Hybrid Drugs 
      with Dual Biological Active Sites.
LID - 10.3390/ijms20225635 [doi]
LID - 5635
AB  - The present study aimed to test the anti-inflammatory and xanthine oxidase 
      inhibitory activities of two synthesized molecules and compare them to routinely 
      prescribed nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac and 
      the serum urate-lowering drug, allopurinol. The anti-inflammatory effects of the 
      designed compounds (A and B) were evaluated in carrageenan (CAR)-induced paw 
      edema in mice. The levels of nitric oxide and myeloperoxidase activity were 
      measured in paw skin using biochemical methods. Additionally, prostaglandin E2 
      (PGE2), C-reactive protein (CRP), cyclooxygenase-2 (Cox-2), tumor necrosis 
      factor-alpha (TNFalpha), interleukin (IL)-1beta, IL-2 and IL-10, and monocyte 
      chemoattractant protein-1 (MCP1) were assessed by enzyme-linked immunosorbent 
      assay (ELISA). The expression of inflammation-related genes was confirmed by 
      real-time qPCR. The expression of inducible nitric oxide synthase (iNOS) and 
      nuclear factor-kappa B (NF-kappaB) were estimated using immunohistochemistry, and 
      xanthine oxidase inhibitory activity was evaluated using an in vitro assay. The 
      results revealed that compounds A and B decreased inflammation, as was observed 
      by a reduction in the elevation of all the tested markers. In addition, the 
      tested compounds markedly decreased paw swelling, mobilization of inflammatory 
      cells, iNOS-, and NF-kappaB-immunoreactive cells in a mouse model of paw edema. 
      Interestingly, both compounds were potent xanthine oxidase inhibitors as well as 
      Cox inhibitors with higher activity in favor of compound B providing potential 
      dual acting series of anti-hyperuricemic and anti-inflammatory therapeutic 
      agents.
FAU - Almeer, Rafa S
AU  - Almeer RS
AUID- ORCID: 0000-0002-1624-3109
AD  - Department of Zoology, College of Science, King Saud University, Riyadh 11451, 
      Saudi Arabia.
FAU - Hammad, Sherif F
AU  - Hammad SF
AUID- ORCID: 0000-0001-8869-5967
AD  - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, 
      Cairo 11795, Egypt.
FAU - Leheta, Ola F
AU  - Leheta OF
AD  - Clinical Pathology Department, Faculty of Medicine, Suez Canal University, 
      Ismalia 41522, Egypt.
FAU - Abdel Moneim, Ahmed E
AU  - Abdel Moneim AE
AUID- ORCID: 0000-0002-2654-2591
AD  - Department of Zoology and Entomology, Faculty of Science, Helwan University, 
      Cairo 11795, Egypt.
FAU - Amin, Hatem K
AU  - Amin HK
AD  - Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Helwan 
      University, Cairo 11795, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20191111
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Gout Suppressants)
RN  - 0 (Interleukins)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.17.3.2 (Xanthine Oxidase)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/chemistry/*pharmacology/therapeutic use
MH  - C-Reactive Protein/analysis
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Cyclooxygenase 2/metabolism
MH  - Dinoprostone/metabolism
MH  - Edema/*drug therapy
MH  - Gout Suppressants/chemistry/*pharmacology/therapeutic use
MH  - Interleukins/metabolism
MH  - Male
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Peroxidase/metabolism
MH  - Skin/drug effects/metabolism/pathology
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Xanthine Oxidase/antagonists & inhibitors
PMC - PMC6888696
OTO - NOTNLM
OT  - allopurinol
OT  - arthritis
OT  - diclofenac
OT  - febuxostat
OT  - inflammation
OT  - paw edema
OT  - xanthine oxidase
COIS- The authors declare no conflict of interest.
EDAT- 2019/11/14 06:00
MHDA- 2020/04/01 06:00
PMCR- 2019/11/01
CRDT- 2019/11/14 06:00
PHST- 2019/10/16 00:00 [received]
PHST- 2019/10/31 00:00 [revised]
PHST- 2019/11/04 00:00 [accepted]
PHST- 2019/11/14 06:00 [entrez]
PHST- 2019/11/14 06:00 [pubmed]
PHST- 2020/04/01 06:00 [medline]
PHST- 2019/11/01 00:00 [pmc-release]
AID - ijms20225635 [pii]
AID - ijms-20-05635 [pii]
AID - 10.3390/ijms20225635 [doi]
PST - epublish
SO  - Int J Mol Sci. 2019 Nov 11;20(22):5635. doi: 10.3390/ijms20225635.