2-Phenylbenzothiazoles featuring heteroaryl sulfonamide end-capping substructures as developable mPGES-1 inhibitors

Yalcin T., Jordan P. M., OLĞAÇ A., Dahlke P., GÜR MAZ Z. T., BANOĞLU E., ...Daha Fazla

ARCHIV DER PHARMAZIE, cilt.358, sa.1, 2025 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 358 Sayı: 1
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1002/ardp.202400756
  • Dergi Adı: ARCHIV DER PHARMAZIE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, International Pharmaceutical Abstracts, Veterinary Science Database
  • Gazi Üniversitesi Adresli: Evet

Özet

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 mu M 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 mu M) 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.