Synthesis, Anion‐Binding Properties, and In Vitro Anticancer Activity of Prodigiosin Analogues

Sessler, Jonathan L.; Eller, Leah R.; Cho, Won‐Seob; Nicolaou, Sergios; Aguilar, Apolonio; Lee, Jeong Tae; Lynch, Vincent M.; Magda, Darren

doi:10.1002/ange.200501740

Cited by 61 publications

(46 citation statements)

References 23 publications

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“…The cis isomer ( 23 or 25b ) is believed to possess an optimal juxtaposition of functional groups for activities such as anion transport and cation binding. 77,78 An evolutionary advantage may therefore be conferred on bacteria that have evolved oxidative carbocyclization enzymes (e.g., RedG and McpG) that allow the C ring of prodigiosin and undecylprodigiosin to be functionalized at the carbon atom directly adjacent to the azafulvene core. Such functionalization generates significant 1,3-allylic strain in the trans isomer.…”

Section: Isolation and Structural Elucidationmentioning

confidence: 99%

Structure, Chemical Synthesis, and Biosynthesis of Prodiginine Natural Products

et al. 2016

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The prodiginine family of bacterial alkaloids is a diverse set of heterocyclic natural products that have likely been known to man since antiquity. In more recent times, these alkaloids have been discovered to span a wide range of chemical structures that possess a number of interesting biological activities. This review provides a comprehensive overview of research undertaken toward the isolation and structural elucidation of the prodiginine family of natural products. Additionally, research toward chemical synthesis of the prodiginine alkaloids over the last several decades is extensively reviewed. Finally, the current, evidence-based understanding of the various biosynthetic pathways employed by bacteria to produce prodiginine alkaloids is summarized.

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Section: Isolation and Structural Elucidationmentioning

confidence: 99%

Structure, Chemical Synthesis, and Biosynthesis of Prodiginine Natural Products

et al. 2016

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“…However, several carrier systems have been reported that induce apoptosis. For instance, prodigiosin (a naturally occurring small-molecule-based ion transporter) and its analogues are known to induce cancer cell death by altering intracellular pH gradients through HCl transport 16–18 . Recently, we found that a synthetic diamide-strapped calix[4]pyrrole 1 (Fig.…”

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confidence: 99%

A synthetic ion transporter that disrupts autophagy and induces apoptosis by perturbing cellular chloride concentrations

et al. 2017

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Perturbations in cellular chloride concentrations can affect cellular pH and autophagy and lead to the onset of apoptosis. With this in mind, synthetic ion transporters have been used to disturb cellular ion homeostasis and thereby induce cell death; however, it is not clear whether synthetic ion transporters can also be used to disrupt autophagy. Here, we show that squaramide-based ion transporters enhance the transport of chloride anions in liposomal models and promote sodium chloride influx into the cytosol. Liposomal and cellular transport activity of the squaramides is shown to correlate with cell death activity, which is attributed to caspase-dependent apoptosis. One ion transporter was also shown to cause additional changes in lysosomal pH, which leads to impairment of lysosomal enzyme activity and disruption of autophagic processes. This disruption is independent of the initiation of apoptosis by the ion transporter. This study provides the first experimental evidence that synthetic ion transporters can disrupt both autophagy and induce apoptosis.

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“…Sessler and coworkers reported the NH hydrogen bonding-based complexation between the protonated dipyrrins 16 and 17 (Figure 9) and for chloride anion (added as a TBA salt). In CH 3 CN solution, association constants of 8.8 × 10 5 and 3.0 × 10 5 M −1 , respectively, were determined by isothermal titration calorimetry (ITC) [47]. Other examples of complexation of anionic zinc salts were published by Dolphin and coworkers [48].…”

Section: Dipyrrin- Dipyrrinone- and Dipyrromethane-based Anion Rementioning

confidence: 99%

“…In 2005, Sessler and coworkers reported the chloride transport properties of the synthetic prodigiosin 41 through vesicle membranes via a co-transport H + /Cl − mechanism [47]. An X-ray diffraction analysis of 41 revealed a chloride anion hydrogen bonded to three NH sites [47].…”

Section: Prodigiosin- Tambjamine- and Perenosin-based Anion Recepmentioning

confidence: 99%

Pyrrole N–H anion complexes

Vargas‐Zúñiga

Sessler

2017

Coordination Chemistry Reviews

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Synthetic pyrrole-based anion receptors date back to the 1990s. They have been extensively developed in the context of macrocyclic systems as expanded porphyrins and calixpyrroles, and related systems. The chemistry of open-chain pyrrolic systems is, in many respects, no less venerable. It also has more direct analogy to naturally occurring pyrrole-based anion binding motifs. However, it has not been the subject of a comprehensive review. Presented herein is a summary of efforts devoted to the creation of de novo pyrrole-based receptors, as well as the anion recognition chemistry of naturally occurring pyrrolic systems as prodigiosins and their synthetic analogues.

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Synthesis, Anion‐Binding Properties, and In Vitro Anticancer Activity of Prodigiosin Analogues

Cited by 61 publications

References 23 publications

Structure, Chemical Synthesis, and Biosynthesis of Prodiginine Natural Products

Structure, Chemical Synthesis, and Biosynthesis of Prodiginine Natural Products

A synthetic ion transporter that disrupts autophagy and induces apoptosis by perturbing cellular chloride concentrations

Pyrrole N–H anion complexes

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