Design of novel dispirooxindolopyrrolidine and dispirooxindolopyrrolothiazole derivatives as potential antitubercular agents.
Mhiri C, Boudriga S, Askri M, Knorr M, Sriram D, Yogeeswari P, Nana F, Golz C, Strohmann C.
With the aim to develop new potent antitubercular agents, a series of novel dispirooxindolopyrrolidines and dispirooxindolopyrrolothiazoles have been synthesized via a three-component 1,3-dipolar cycloaddition of (Z)-3-arylidenebenzofuran-2-ones, substituted isatin derivatives and α-aminoacids. The stereochemistry of the spiroadducts has been confirmed by an X-ray diffraction analysis. All the target heterocycles were evaluated for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv strain and the most active compounds were subjected to cytotoxicity studies against (RAW 264.7) cell lines. Among them, twelve compounds showed potent anti-tubercular activity with MIC ranging from 1.56 to 6.25 μg/mL. In particular dispirooxindolopyrrolothiazole derivatives 5c and 5f were found to be the most active (MIC of 1.56 μg/mL) with a good safety profile (27.53% and 20.74% at 50 μM, respectively). This is the first report demonstrating the benzofuranone oxindole hybrids as potential antimycobacterial agents.