Design, synthesis, antitubercular and antiviral properties of new spirocyclic indole derivatives

Cihan-Üstündağ, Gökçe; Naesens, Lieve; Şatana, Dilek; Erköse-Genç, Gonca; Mataracı-Kara, Emel; Çapan, Gültaze

ABSTRACT: A series of indole-based spirothiazolidinones have been designed, synthesized and evaluated, in vitro, for their antitubercular, antiviral, antibacterial, and antifungal activities. The structures of the new compounds were established by IR, (1)H NMR, (13)C NMR (proton decoupled, APT, and DEPT), electrospray ionization mass spectrometry, and microanalysis. Compounds bearing a phenyl substituent at position 8 of the spiro ring, exhibited significant antitubercular activity against Mycobacterium tuberculosis H37Rv ATCC 27294 at concentrations of 3.9 and 7.8 µM. Still, some of the tested compounds displayed activity on mycobacteria with MIC values of 16 and 31 µM. Four of the indole-spirothiazolidinone derivatives were found to be moderately active against Punta Toro virus, yellow fever virus or Sindbis virus in Vero cells. The antiviral EC(50) values were in the range of 1.9–12 µM and the selectivity index (ratio of cytotoxic to antivirally effective concentration) was above 10 in some cases. The most potent effect was seen with the compound that is methylated at positions 2 and 8 of the spirothiazolidinone system. GRAPHIC ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00706-019-02457-9) contains supplementary material, which is available to authorized users.