Synthesis of new N-(3-oxo-1-thia-4-azaspiro[4.5]decan-4-yl)pyridine-3-carboxamide derivatives and evaluation of their anti-influenza virus and antitubercular activities

Cihan-Ustundag G., Acar C., Naesens L., Erkose-Genc G., Satana D.

ARCHIV DER PHARMAZIE, cilt.355, sa.10, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 355 Sayı: 10
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1002/ardp.202200224
  • 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, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: antitubercular activity, antiviral activity, influenza virus, nicotinohydrazide, spirothiazolidinone, SCAFFOLDS
  • İstanbul Üniversitesi Adresli: Evet

Özet

We here report the synthesis, structural characterization, and evaluation of the antiviral and antitubercular activities of a novel series of hybrid spirothiazolidinone derivatives (2a-f and 3a-f) containing the nicotinohydrazide moiety, which is an isomer form of the approved antitubercular drug isoniazid. When evaluated for activity against influenza A/H1N1, A/H3N2, and B viruses, three of the new compounds proved to possess specific antiviral activity against the influenza A/H3N2 virus. The most active analog 3a, bearing a 2,8-dimethyl group at the spiro ring, displayed an antiviral EC50 value of 5.2 mu M. Compound 3a produced no cytotoxicity at 100 mu M, the highest concentration tested, giving a selectivity index of at least 19. Structure-activity relationship analysis indicated that the absence of the methyl substituent at the 2-position and the presence of a bulky substituent at the 8-position of the spirothiazolidinone system caused a significant decrease in antiviral activity. The in vitro antitubercular activity of compounds 2a-f and 3a-f was determined for six different drug-sensitive/drug-resistant laboratory strains and clinical isolates of Mycobacterium tuberculosis. Compounds 2c, 2d, 3b, 3c, and 3d showed weak antitubercular activity against different strains, with MIC values of 125-250 mu M.