Synthesis of turbomicin-based alkaloids through infrared light-induced multicomponent reactions and assessment of their cytotoxic and antifungal bioactivity

The cytotoxic and antifungal capacity of a set of turbomycin-based alkaloids, assembled by multicomponent reactions through exposure to near-infrared light (λ = 1.1 μm) in the presence of organic acid, was tested against six cancer cell lines (SW620, SW480, HeLa, K562, MCF-7, and Calo) and three life-threatening fungi (C. albicans, C. parapsilosis, and C. neoformans). Notably, the structurally elaborated compounds (> 10³ Da) showed an antifungal effect against C. parapsilosis and C. neoformans at a concentration of 2.4 mM comparable to ketoconazole (22 vs. 20 mm). In contrast, its lower molecular weight homologous (< 500 Da) exhibited substantially the best cytotoxic effect against the growth of the colon adenocarcinoma cell lines SW620 and WS408 (IC₅₀ = 12.56 ± 3.3 μmol and 13.9 ± 2.7 μmol), values slightly higher than the m-AMSA positive control (IC₅₀ = 8.3 ± 2.6 and 7.4 ± 2.04 μmol). Highlight that only regioisomers containing the 1,1′-dimethyl-, 2,2′-dimethyl-, and 2,2′-diphenyl-DIM subunits attached on phenyl ring in a 1,3-substitution pattern exhibit substantial cytotoxic and antifungal effect. Graphic abstract: