Tansu Yalçın, Paul M. Jordan, Abdurrahman Olğaç, Philipp Dahlke, Tuğçe Gür Maz, Erden Banoglu, Oliver Werz, Burcu Çalışkan
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2-Phenylbenzothiazoles featuring heteroaryl sulfonamide end-capping substructures as developable mPGES-1 inhibitors
The inhibition of human microsomal prostaglandin E2 (PGE2) synthase-1 (mPGES-1) is a promising therapeutic modality for developing next-generation anti-inflammatory medications. In this study, we present novel 2-phenylbenzothiazole derivatives featuring heteroaryl sulfonamide end-capping substructures as inhibitors of human mPGES-1, with IC50 values in the range of 0.72–3.40 µM in a cell-free assay of PGE2 formation. Notably, compound 21, featuring a quinoxalinedione ring in its sulfonamide segment, effectively suppresses PGE2 biosynthesis at a low micromolar concentration (IC50 = 0.72 µM) with exceptional selectivity against cyclooxygenase (COX)-1, COX-2, 5-lipoxygenase (5-LOX), and FLAP. This compound offers a novel chemical scaffold for developing safer and more effective anti-inflammatory agents.
期刊介绍：
Archiv der Pharmazie - Chemistry in Life Sciences is an international journal devoted to research and development in all fields of pharmaceutical and medicinal chemistry. Emphasis is put on papers combining synthetic organic chemistry, structural biology, molecular modelling, bioorganic chemistry, natural products chemistry, biochemistry or analytical methods with pharmaceutical or medicinal aspects such as biological activity. The focus of this journal is put on original research papers, but other scientifically valuable contributions (e.g. reviews, minireviews, highlights, symposia contributions, discussions, and essays) are also welcome.
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