Prototyping kinase inhibitor-cytotoxin anticancer mutual prodrugs activated by tumour hypoxia: A chemical proof of concept study
Graphical abstract
Section snippets
Funding sources
Funded in part by a Health Research Council of New Zealand grant 17/255 to Jeff Smaill and Adam Patterson and Australian National Health and Medical Research Council (NHMRC) Project Grant (APP1100432) to Michael Kelso.
Acknowledgment
We thank the University of Wollongong (Wollongong, Australia) and University of Auckland (Auckland, NZ) for supporting this work.
References (30)
- et al.
Prodrug-based intracellular delivery of anticancer agents
Adv Drug Del Rev
(2011) Prodrug strategies in cancer therapy
Eur J Med Chem
(2001)Targeted delivery of chemotherapeutics: tumor-activated prodrug therapy
Adv Drug Del Rev
(1998)- et al.
Prodrugs for improving tumor targetability and efficiency
Adv Drug Del Rev
(2011) - et al.
A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia
Blood
(2003) - et al.
Unexpected synthesis of 3-imino-2-(pyrrol-2-yl) isatogen derivatives affords facile access to a 2-pyrrolyl isatogen
Synth Commun
(2017) - et al.
Synthesis and preliminary evaluation of 5,7-dimethyl-2-aryl-3H-pyrrolizin-3-ones as angiogenesis inhibitors
Bioorg Med Chem Lett
(2016) - et al.
Rapid, efficient and selective reduction of aromatic nitro compounds with sodium borohydride and Raney nickel
J Mol Catal A Chem
(2007) - et al.
Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99–06): a randomised trial
Lancet
(2007) - et al.
SR-4233: a new bioreductive agent with high selective toxicity for hypoxic mammalian cells
Int J Radiat Oncol Biol Phys
(1986)
Design of anticancer prodrugs for reductive activation
Med Res Rev
Hypoxia-activated prodrugs in cancer therapy: progress to the clinic
Future Oncol
Targeting hypoxia in cancer therapy
Nat Rev Cancer
Hypoxia-activated prodrugs: paths forward in the era of personalised medicine
Br J Cancer
Relationships between structure and kinetics of cyclization of 2-aminoaryl amides: potential prodrugs of cyclization-activated aromatic mustards
J Med Chem
Cited by (7)
A novel and unexpected one pot synthesis of pyrrolo[1,2-a]quinolines
2022, Tetrahedron LettersCitation Excerpt :Allyl esters 6–11 were prepared in good yields from commercial fluorinated and trifluoromethylated 2-(2-nitrophenyl)acetic acids by esterification using catalytic H2SO4 and allyl alcohol (ESI). Pyrrole aldehyde 3 was prepared using the published method [1]. The first attempted Knoevenagel reaction with 4-fluorinated allyl ester 6 and aldehyde 3 under the reported conditions (K2CO3, 2.0 eq., 18-crown-6, 0.5 eq., THF/reflux; Table 1, Entry 2) produced the expected alkenes (Z)-12 and (E)-12, albeit in only 7% and 10% yields, respectively, as red solids.
Hypoxia-activated nanomedicines for effective cancer therapy
2020, European Journal of Medicinal ChemistryCitation Excerpt :Finally, we focus on the applications of anaerobic-bacteria-mediated targeting of tumor hypoxia. Hypoxic conditions can result in cellular dysfunction and injury [48,49]. Recently, several hypoxia-associated mechanisms that regulate the cellular response to autophagy have been identified, such as the HIF-1 pathway, the mammalian target of rapamycin (mTOR), and the unfolded protein response (UPR) [50].
Mutual Prodrugs-Codrugs
2023, Current Medicinal ChemistryNitroaromatic Hypoxia-Activated Prodrugs for Cancer Therapy
2022, PharmaceuticalsTherapeutic targeting of the hypoxic tumour microenvironment
2021, Nature Reviews Clinical OncologyFloxuridine Oligomers Activated under Hypoxic Environment
2021, Journal of the American Chemical Society