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Anti-Inflammatory and Anti-Hyperuricemic Functions of Two Synthetic Hybrid Drugs With Dual Biological Active Sites

Anti-Inflammatory and Anti-Hyperuricemic Functions of Two Synthetic Hybrid Drugs With Dual Biological Active Sites

Rafa S Almeer, Sherif F Hammad, Ola F Leheta, Ahmed E Abdel Moneim, Hatem K Amin

Int J Mol Sci. 2019 Nov 11;20(22):5635.

PMID: 31718011

Abstract:

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-α (TNFα), interleukin (IL)-1β, 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-κB) 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-κB-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.

Chemicals Related in the Paper:

Catalog Number	Product Name	CAS Number	Price
AP1346604134	Allopurinol Related Compound C	1346604-13-4	Price
AP15362400-B	Diclofenac related compound A	15362-40-0	Price
AP22407201	Allopurinol Related Compound B	22407-20-1	Price
AP27511791	Allopurinol Related Compound A	27511-79-1	Price

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