Design, Synthesis, and In Vitro and In Silico Anticancer Profiling of Spirooxindole–Tetrahydrocarbazoles

Abstract

An efficient and feasible method has been developed for the synthesis of spirooxindole-tetrahydrocarbazole (SOTC) derivatives via AlCl3-catalyzed cascade approach. This one-pot protocol enables rapid access to structurally diverse spiro-fused carbazole scaffolds, which are of significant interest in medicinal chemistry. The reaction proceeds under mild conditions, offering a broad substrate scope with excellent yields. A library of 28 novel compounds is synthesized and evaluated for anticancer activity using in vitro cytotoxicity and in silico molecular docking studies. Among them, nine compounds exhibit >50% growth inhibition in A549 lung cancer cells, and compound 8 shows the highest cytotoxic activity with an IC50 value of 69.5 µM (A549). Additionally, three compounds demonstrate cytotoxic activity in SKOV3 ovarian cancer cells. These results highlight the potential of SOTC scaffolds as promising leads for further anticancer drug development. Taken altogether, the combination of synthetic efficiency, in silico evaluation, and anticancer activities will pave the way for these compounds to act as promising candidates for anticancer drug development. © 2026 Wiley-VCH GmbH.