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. 2023 Nov:140:106782.
doi: 10.1016/j.bioorg.2023.106782. Epub 2023 Aug 21.

Synthesis and in vitro cytotoxic activity of dye-linker-macrocycle conjugates with variable linker length and components

Mateusz D Tomczyk  1 , Karolina Matczak  2 , Magdalena Skonieczna  3 , Pavel Chulkin  4 , Marta Denel-Bobrowska  5 , Daria Różycka  5 , Sebastian Rykowski  5 , Agnieszka B Olejniczak  5 , Krzysztof Walczak  6
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Free article

Synthesis and in vitro cytotoxic activity of dye-linker-macrocycle conjugates with variable linker length and components

Mateusz D Tomczyk et al. Bioorg Chem. 2023 Nov.
Free article

Abstract

The study investigated the structure-activity relationship of newly synthesized dye-linker-macrocycle (DLM) conjugates and the effect of each component on various biological properties, including cytotoxicity, cellular uptake, intracellular localization, interaction with DNA and photodynamic effects. The conjugates were synthesized by combining 1,8-naphthalimide and thioxanthone dyes with 1,4,7,10-tetraazacyclododecane (cyclen) and 1-aza-12-crown-4 (1A12C4) using alkyl linkers of different lengths. The results revealed significant differences in biological activity among the various series of conjugates. Particularly, 1A12C4 conjugates exhibited notably higher cytotoxicity compared to cyclen conjugates. Conjugation with 1A12C4 proved to be an effective strategy for increasing cellular uptake and cytotoxicity of small-molecule conjugates. In addition, the results highlighted the critical role of linker length in modulating the biological activity of DLM conjugates. It became clear that the choice of each component (dye, macrocycle and linker) could significantly alter the biological activity of the conjugates.

Keywords: 1,8-Naphthalimide; Crown ethers; Cyclic polyamines; Cytotoxic activity; Thioxanthone.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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