Ultrasonication-ionic liquid synergy for the synthesis of new potent anti-tuberculosis 1,2,4-triazol-1-yl-pyrazole based spirooxindolopyrrolizidines

• Published in: Bioorganic & medicinal chemistry letters Vol. 29; no. 13; pp. 1682 - 1687
• Main Authors: Pogaku, Vinay, Krishna, Vagolu Siva, Sriram, Dharmarajan, Rangan, Krishnan, Basavoju, Srinivas
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.07.2019; Elsevier
• Subjects: Anti-tuberculosis activity; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Cytotoxicity; Green methodology; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Spirooxindoles; Ultrasonication-ionic liquid synergy; Spirooxindoles; Anti-tuberculosis activity; Cytotoxicity; Ultrasonication-ionic liquid synergy; Green methodology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2019.04.026

[Display omitted] •New potent anti-TB spirooxindolopyrrolizidines were designed & synthesized by green methodology.•High yields of the products in less reaction time and reusability of the ionic liquid.•Dept-135 and crystallographic studies of the compound 6f.•Anti-TB activity evaluation of all compounds & identifying leads (6h, 6e, 6k, 6l, 6n, 6q &6r) as promising anti-TB agents.•6 compounds exhibited anti-TB activity equal to drug Ethambutol and 1 compound exhibited superior activity than ethambutol. The aim of the study is to design and synthesis of a new series of potent anti-TB 1,2,4-triazol-1-yl-pyrazole based spirooxindolopyrrolizidines with their safety profile. A synergetic effect of ultrasonication and ionic liquid was shown successfully as a green methodology for the synthesis of title compounds 6a–t. These derivatives were obtained in shorter reaction time with good yields and well characterized by various spectroscopic methods, single-crystal X-ray diffraction (6f). The in vitro anti-tuberculosis activity for newly-synthesized derivatives has been screened against Mycobacterium tuberculosis. Among all, six compounds 6e, 6k, 6l, 6n, 6q and 6r exhibited equal potent activity compared to standard drug ethambutol (MIC: 1.56 µg/mL) and another compound 6h exhibited outstanding activity (MIC: 0.78 µg/mL) than the standard drug ethambutol. Cytotoxic nature of the anti-TB active compounds was evaluated against RAW 264.7 cells. The 6h, 6e, 6k, 6l, 6n, 6q and 6r exhibited lower toxicity which could be promising hits for anti-tuberculosis.