Design, synthesis, and apoptotic evaluation of spiro[indoline-3,3′-pyrazolo[1,2-a]indazole] derivatives via [3 + 2] N,N-cycloaddition†

Abstract

An efficient protocol for the synthesis of spiro[indoline-3,3′-pyrazolo[1,2-a]indazole] derivatives was developed via a [3 + 2] N,N-cycloaddition strategy, utilizing substituted 2-(2-oxoindolin-3-ylidene)malononitrile derivatives and 1,2-dihydro-3H-indazol-3-one under mild conditions, yielding excellent results (3a–3l). Furthermore, selected derivatives (3e and 3h–3l) were evaluated for cytotoxicity against various cancer cell lines, including MCF-7 (breast cancer), A549 (lung cancer), Colo-205 (colon cancer), and A2780 (ovarian cancer). The IC₅₀ values ranged from 1.34 ± 0.21 μM (for 3l against MCF-7) to 8.53 ± 1.49 μM (for 3h against A2780). Notably, derivative 3l demonstrated the most potent apoptotic activity, exhibiting the lowest IC₅₀ values across all four cancer cell lines. Additionally, molecular docking studies corroborated the observed biological activity, suggesting that these compounds may interact with relevant cellular targets, potentially accounting for their cytotoxic effects.