A Synthetic Approach for the Rapid Preparation of BODIPY Conjugates and their use in Imaging of Cellular Drug Uptake and Distribution

Abstract

A solid-phase synthetic (SPS) method was developed for the preparation of BODIPY-labeled bioactive compounds that allows for fast and simple synthesis of conjugates for use in fluorescent microscopy. The approach was used to visualize cellular uptake and distribution of cytotoxic triterpenes in cancer cells.

Recent Developments in the Functionalization of Betulinic Acid and Its Natural Analogues: A Route to New Bioactive Compounds

“…These carrier systems are usually developed to stabilize therapeutic compounds, overcoming obstacles to cellular and tissue uptake, improving biodistribution, bioavailability, and therapeutic efficacy, and decreasing the side effects of compounds that target specific sites in vivo. Only a few articles have been published describing the preparation of BA‒polymer conjugates since 2013 [83,84,85,86,87]. Although the synthesis of polymer‒BA conjugates involves mainly amination and esterification reactions, it makes more sense to create a specific section to approach this theme.…”

“…Krajcovicova et al prepared boron-dipyrromethene (BODIPY)-labeled BA conjugates 157 – 159 for use in fluorescent microscopy [86]. Live cell studies focused on fluorescence conjugate uptake demonstrated a specific labeling pattern of conjugates 157 – 159 .…”

Solid-phase fluorescent BODIPY–peptide synthesis via in situ dipyrrin construction

“…BODIPYpeptide conjugates are therefore widely used as dual targetingimaging tools in life sciences, 7,[48][49][50][51][52][53][54] although a "uorescent postlabelling" strategy has to be used since BODIPY derivatives are generally vulnerable to strong acid and usually not so adaptable to SPPS conditions. [55][56][57] To this end, Vendrell et al documented the rst "uorescent building block" approach by developing a uorogenic Trp-BODIPY amino acid in a spacer-free manner (i.e. direct carbon-carbon bond linkage between a tryptophan's indole moiety at the C2-position and a BODIPY dye by palladium-catalyzed C sp2 -C sp2 Heck reaction).…”

Synthesis and cytotoxic evaluation of malachite green derived oleanolic and ursolic acid piperazineamides

“…Thus, hybrids holding an extra cationic functional group have shown promising to excellent cytotoxic results. While "simple" quaternary ammonium salts (Biedermann et al 2010;Kataev, Strobykina, and Zakharova 2014) were only of moderate cytotoxicity with their EC 50 values being in the same potency range as phosphonium salts (Spivak et al 2017(Spivak et al , 2013, hybrids consisting of a suitable pentacyclic triterpene, an amine spacer and a BODIPY-FL group (Brandes et al 2020;Krajcovicova et al 2018) held lower EC 50 values against a variety of different human cancer cell lines. Superior cytotoxicity, however, was found for those triterpenoids holding one or two O-acetyl groups on ring A, an amide spacer at C-28 (preferentially a piperazinyl residue), and a rhodamine B moiety attached to this spacer (Sommerwerk et al 2017).…”