Fluorescence Characterization and Cellular Localization of the Mesoionic Compound MIH 2.4Bl

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2021

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Mathis, James
Debnath, Dipti
Souza, Helivaldo
Filho, Petrônio
Fudala, Rafal
Zhang, Jinmin

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Abstract

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women worldwide, making this disease a critical public health problem. Mesoionic compounds, which possess a 5-membered heterocyclic aromatic ring associated with a sextet of electrons, have shown remarkable promise as anti-cancer agents due to their unique structure and reaction properties. We previously reported the synthesis of a new 1,3-thiazolium-5-thiolate derivative of the mesoionic class (MIH 2.4Bl) and characterization of its selective cytotoxicity in a panel of breast cancer cell lines. Our studies suggest that treatment with MIH 2.4Bl mediates apoptotic death in breast cancer cells through mitochondrial dysfunction. To advance potential translational studies toward therapeutic applications, we have begun studies of the fluorescence properties of MIH 2.4Bl, using steady-state and time-resolved fluorescence techniques. Our preliminary steady-state measurements showed that the absorption spectrum of the drug is similar in different tested solvents. All samples, dissolved in various solvents, exhibited maximum absorbance between 440 and 480 nm; excitation at 480 nm elicited the highest emission at approximately 615 nm. These results may allow for future detection and localization of MIH 2.4Bl in vitro and in vivo. Follow-up studies utilizing fluorescence confocal microscopy are anticipated to reveal the site(s) of drug accumulation in situ and how cytotoxicity is induced in cancer cells. In addition, fluorescence lifetime measurements will be conducted to provide assessments of changes in the macromolecular conformational and experimental dynamic range of the drug.

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