Synthesis and characterization of photolabeling probes of miltefosine

Synthesis and Biological Evaluation of Fluorescent Leishmanicidal Analogues of Hexadecylphosphocholine (Miltefosine) as Probes of Antiparasite Mechanisms

“…The leishmanicidal activity of this compound ( in vitro ) is identical to that of the parent drug . Finally, a few analogues have been obtained incorporating reporter probes such as a tetrafluorophenylazido group for photolabeling purposes, or a nitroxide paramagnetic group at position 12 of octadecylphosphocholine …”

Photoactivatable Phospholipids Bearing Tetrafluorophenylazido Chromophores Exhibit Unprecedented Protonation-State-Dependent 19F NMR Signals

“…However, studying these biomembranes is extremely challenging due to their heterogeneous mosaic composition and limited solubility. Photoactivatable phospholipids are useful tools to investigate biomembranes via a photolabeling approach. , In our effort to develop stable and efficient photoactivatable phospholipidic probes, we are particularly interested in using tetrafluorophenylazide moieties as photoactive chromophores. , This is due to much more efficient photolabeling yielded by the fluorinated aryl azides compared to their nonfluorinated counterparts thanks to considerable stabilization of the reactive arylnitrene intermediates by the electronegative fluorine atoms and the resulting longer half-life . Moreover, the presence of fluorine atoms , provides a unique advantage in 19 F NMR based investigations of biological processes thanks to the absence of fluorinated compounds in most biological samples which could otherwise give rise to interfering background signals.…”

Photoactivatable Lipid Probes for Studying Biomembranes by Photoaffinity Labeling

“…84,85 Moreover, a fluorinated phenyl azide was also used by Huang et al in the synthesis of the photoactivatable analogues of hexadecylphosphocholine (miltefosine) with a tetrafluorophenylazido chromophore incorporated either at the polar head (22 in Figure 13) or in the long alkyl chain (23 in Figure 13). 86 It is worth mentioning that miltefosine is an alkylphosphocholine showing remarkable antineoplastic, antitumor, and antileishmanial activities. 87 Aside from the above-mentioned probes, the bola-lipid probes (Figure 5) are particularly appealing for studying biomembranes due to their unique structure and specific labeling of the transmembrane domain.…”