Reversible derivatization to enhance enzymatic synthesis: Chemoenzymatic synthesis of doxorubicin‐14‐<i>O</i>‐esters

Cotterill, Ian C.; Rich, Joseph O.; Scholten, Marc D.; Mozhaeva, Lyudmila; Michels, Peter C.

doi:10.1002/bit.21929

Cited by 5 publications

(4 citation statements)

References 26 publications

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“…Next, pDOX was synthesized by acylation and characterized using both 1 H NMR spectroscopy and electrospray ionization mass spectrometry (ESI–MS) . The ESI–MS spectrum of pDOX showed the highest m / z values at 650.5 (Figure S3).…”

Section: Resultsmentioning

confidence: 99%

“…Next, pDOX was synthesized by acylation and characterized using both 1 H NMR spectroscopy and electrospray ionization mass spectrometry (ESI−MS). 37 The ESI−MS spectrum of pDOX showed the highest m/z values at 650.5 (Figure S3). Furthermore, the 1 H NMR spectrum of pDOX showed the presence of characteristic peaks such as 2.24, 1.98, and 1.27 ppm, indicating the successful synthesis of pDOX (Figure S4).…”

Section: Resultsmentioning

confidence: 99%

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Prodrug-Based Nanoreactors with Tumor-Specific In Situ Activation for Multisynergistic Cancer Therapy

Ren

Liu

et al. 2020

ACS Appl. Mater. Interfaces

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Efficient drug delivery into tumor cells while bypassing many biological barriers is still a challenge for cancer therapy. By taking advantage of the palladium (Pd)-mediated in situ activation of a prodrug and the glucose oxidase (GOD)-based β-Dglucose oxidation reaction, we developed a multisynergistic cancer therapeutic platform that combined doxorubicin (DOX)-induced chemotherapy with GOD-mediated cancer-orchestrated oxidation therapy and cancer starvation therapy. In the present work, we first synthesized DOX prodrugs (pDOXs) and temporarily assembled them with β-cyclodextrins to reduce their toxic side effects. Then, a nanoreactor was constructed by synthesizing Pd 0 nanoparticles in situ within the pores of mesoporous silica nanoparticles for the conversion of pDOX into the active anticancer drug. Furthermore, GOD was introduced to decrease the pH of the tumor microenvironment and induce cancer-orchestrated oxidation/starvation therapy by catalyzing β-D-glucose oxidation to form hydrogen peroxide (H 2 O 2 ) and gluconic acid. Our study provides a new strategy that employs a cascade chemical reaction to achieve combined orchestrated oxidation/starvation/chemotherapy for the synergistic killing of cancer cells and the suppression of tumor growth.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Prodrug-Based Nanoreactors with Tumor-Specific In Situ Activation for Multisynergistic Cancer Therapy

Ren

Liu

et al. 2020

ACS Appl. Mater. Interfaces

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“…Cotterill and co-workers 24 have developed an alternative chemoenzymatic synthesis of doxorubicin-14-O-acyl derivatives involving three steps: (1) protection of the amino group of doxorubicin hydrochloride 18ÁHCl with allyl chloroformate, (2) regioselective 14-OH acylation with vinyl hexanoate or heptanoic acid employing CAL-B as a catalyst and a mixture of pyridine : tert-butylic alcohol (45 : 55) as a solvent, and (3) Pd(0)-catalyzed removal of the protecting group.…”

Section: Polyketidesmentioning

confidence: 99%

“…Ion-paired subtilisin Carlsberg (AOT-SC) catalyzes the regioselective preparation of doxorubicin derivatives(23)(24)(25)(26) …”

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confidence: 99%

Regioselective enzymatic acylation of complex natural products: expanding molecular diversity

2011

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Enzymatic catalysis has become a common tool in both academia and industrial chemistry. The efforts of chemists over recent decades have led to the rationalization of the mechanism of action of biocatalysts, which have been routinely incorporated into many synthetic sequences. Nowadays, a further step consists in expanding the application of enzymes to the modification of complex molecular scaffolds common to many pharmaceutical leads isolated from nature. Regioselective enzymatic acylation is a process which has been profitably applied for this purpose in recent times, leading to new drugs with improved activity, stability and pharmacokinetic properties. This tutorial review provides an overview of this subject employing two classes of enzymes, hydrolases and acyltransferases, in the recently concluded decade although some representative older studies are commented upon, if required. We shall place special emphasis on those examples in which the novel acylated derivatives have improved the activity or properties of the parental molecules.

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Synthesis and evaluation of new peptide-linked doxorubicin conjugates as prodrugs activated by prostate-specific antigen

Aloysius

2020

Med Chem Res

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Reversible derivatization to enhance enzymatic synthesis: Chemoenzymatic synthesis of doxorubicin‐14‐O‐esters

Cited by 5 publications

References 26 publications

Prodrug-Based Nanoreactors with Tumor-Specific In Situ Activation for Multisynergistic Cancer Therapy

Prodrug-Based Nanoreactors with Tumor-Specific In Situ Activation for Multisynergistic Cancer Therapy

Regioselective enzymatic acylation of complex natural products: expanding molecular diversity

Synthesis and evaluation of new peptide-linked doxorubicin conjugates as prodrugs activated by prostate-specific antigen

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