Design, synthesis, and structure-activity relationships of GPR35 agonists and antagonists and design, synthesis, and anti-microbial evaluation of pyrazole derivatives

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Manahil Mirghani Ali Abdalhameed (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site:
Mitchell Croatt

Abstract: GPR35, a G protein-coupled receptor (GPCR), was discovered and specified as an orphan receptor in 1998. GPR35 has been described as a prospective therapeutic target as a result of its association with many diseases including type-2 diabetes, nociceptive pain, inflammation, mild mental retardation syndrome, metabolic disorders, and gastric cancer. A GPR35 antagonist benzothiazole was identified via high-throughput screening of approximately 300,000 compounds. Based on the docking of the benzothiazole into a homology model of GPR35, analogs were designed, synthesized, and evaluated as antagonists at GPR35. The study examines various regions of the GPR35 binding site for the benzothiazole ligand. The results provided information that was used as a guide to design and synthesized potent GPR35 ligands. A heterocyclic ring, pyrazole, has gained special consideration as a result of its significant biological properties including anti-cancer, anti-microbial, anti-bacterial, anti-fungal, and anti-inflammatory. Structurally novel pyrazole derivatives were designed, synthesized and evaluated for antagonist activity at the GPR35 receptor. Due to the scarcity in the anti-microbial drugs and limited scaffold with potentially unique mode of action and different resistance mechanism, these pyrazoles were also evaluated for their anti-microbial activity. SAR study on the pyrazole core presented potential antimicrobial agents that will serve as basis for designing and developing novel antimicrobial drugs.

Additional Information

Language: English
Date: 2015
Antimicrobial, Computional chemistry, GPR35, Synthesis
Anti-infective agents
Drugs $x Design

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