Synthesis, antimicrobial activity and acid dissociation constants of methyl 5,5-diphenyl-1-(thiazol-2-yl)pyrrolidine-2-carboxylate derivatives

Nural Y., Gemili M., Ulger M., Sari H., De Coen L. M., ŞAHİN E.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, cilt.28, sa.5, ss.942-946, 2018 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 28 Sayı: 5
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1016/j.bmcl.2018.01.045
  • Dergi Adı: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.942-946
  • Anahtar Kelimeler: M. tuberculosis H37Rv, Antimicrobial, Acid dissociation constant, Pyrrolidine, Thiazole, POTENTIAL ANTIINFLAMMATORY AGENTS, SUBSTITUTED THIAZOLE DERIVATIVES, BIOLOGICAL EVALUATION, MYCOBACTERIUM-TUBERCULOSIS, ANTITUBERCULAR EVALUATION, ANTIBACTERIAL ACTIVITY, DRUG DISCOVERY, PK(A) VALUES, ANTIMYCOBACTERIAL, PYRROLIDINE
  • Atatürk Üniversitesi Adresli: Evet

Özet

In this study, a series of polysubstituted methyl 5,5-diphenyl-1-(thiazol-2-yl)pyrrolidine-2-carboxylate derivatives were designed and synthesized by the cyclization reaction of methyl 1-(benzoylcarbamothioyl)-5,5-diphenylpyrrolidine-2-carboxylates and 2-bromo-1-(4-substituted phenyl) ethanones in 70-96% yield. The starting pyrrolidine derivatives were synthesized via a 1,3-dipolar cycloaddition reaction in 83-88% yield. The stereochemistry of one of these methyl 5,5-diphenyl-1-(thiazol-2-yl)pyrrolidine-2-carboxylate derivatives was characterized by a single crystal X-ray diffraction study and the acid dissociation constants of these compounds were determined. An antimicrobial screening was performed against different bacterial and fungal strains and against the M. tuberculosis H37Rv strain. Interesting antibacterial activity was observed for two compounds against the A. baumannii strain with MIC values of 31.25 mu g/mL (Ampicillin: 125 mu g/mL) and against the M. tuberculosis H37Rv strain with MIC values of 0.98-1.96 mu g/mL (Isoniazid: 0.98 mu g/mL, Ethambutol: 1.96 mu g/mL). Therefore, these structures can be considered as good starting points for the development of new powerful antimycobacterial agents. (C) 2018 Elsevier Ltd. All rights reserved.