Aldose reductase and cancer metabolism: The master regulator in the limelight

Syamprasad, N P; Jain, Siddhi; Rajdev, Bishal; Prasad, Neethu; Kallipalli, Ravindra; Naidu, V.G.M.

doi:10.1016/j.bcp.2023.115528

Cited by 5 publications

(3 citation statements)

References 152 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, 15 human AKRs with over 190 family members have been discovered, which are further divided into six subfamilies (AKR1A, AKR1B, AKR1C, AKR1E, AKR6A, and AKR7A) according to sequence homology and functional similarity. 1–3 They possess a core motif known as the (α/β)8 barrel, which is alternatively referred to as the TIM barrel due to its association with triose phosphate isomerase, a conserved metabolic enzyme. The (α/β)8 barrel represents the prevailing fold observed in protein catalysts, accounting for approximately 10% of all documented enzyme structures.…”

Section: Introductionmentioning

confidence: 99%

“…4 Relevant studies have confirmed that AKRs are closely related to various diseases, including diabetic complications, asthma and even cancers. 1,5,6…”

Section: Introductionmentioning

confidence: 99%

“…Sorbitol is then metabolized to fructose by sorbitol dehydrogenase, thus involving in the occurrence and development of diabetic complications. 1,9 As a well-characterized enzyme, AKR1B10 has a high retinal reductase activity for all-trans-retinaldehyde, which indirectly regulates cell differentiation. 10 It is widely acknowledged that AKR1B1 and AKR1B10 play a pivotal role in the pathology of diabetic complications and are highly expressed in certain cancers, such as breast, ovarian and lung cancer.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Decoding selectivity: computational insights into AKR1B1 and AKR1B10 inhibition

Liu,

Qin,

et al. 2024

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

“…4 Relevant studies have confirmed that AKRs are closely related to various diseases, including diabetic complications, asthma and even cancers. 1,5,6…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Decoding selectivity: computational insights into AKR1B1 and AKR1B10 inhibition

Liu,

Qin,

et al. 2024

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

show abstract

Multi-target anticancer activity of compounds isolated from galls of Pistacia chinensis subsp. integerrima: A mechanistic investigation

Rauf,

Khan,

Nizamani

et al. 2024

Phytochemistry Letters

View full text Add to dashboard Cite

Esterase-Responsive Fluorogenic Prodrugs of Aldose Reductase Inhibitor Epalrestat: An Innovative Strategy toward Enhanced Anticancer Activity

Misra,

Barman,

Bhabak

2024

ACS Appl. Bio Mater.

View full text Add to dashboard Cite

In addition to the conventional chemotherapeutic drugs, potent inhibitors of key enzymes that are differentially overexpressed in cancer cells and associated with its progression are often considered as the drugs of choice for treating cancer. Aldose reductase (AR), which is primarily associated with complications of diabetes, is known to be closely related to the development of cancer and drug resistance. Epalrestat (EPA), an FDA-approved drug, is a potent inhibitor of AR and exhibits anticancer activity. However, its poor pharmacokinetic properties limit its bioavailability and therapeutic benefits. We report herein the first examples of esterase-responsive turn-on fluorogenic prodrugs for the sustained release of EPA to cancer cells with a turn-on fluorescence readout. Carboxylesterases are known to be overexpressed in several organ-specific cancer cells and help in selective uncaging of drug from the prodrugs. The prodrugs were synthesized using a multistep organic synthesis and successfully characterized. Absorption and emission spectroscopic studies indicated successful activation of the prodrugs in the presence of porcine liver esterase (PLE) under physiological condition. HPLC studies revealed a simultaneous release of both the drug and the fluorophore from the prodrugs over time with mechanistic insights. While the inhibitory potential of EPA released from the prodrugs toward the enzyme AR was validated in the aqueous medium, the anticancer activity of the prodrugs was studied in a representative cervical cancer cell line. Interestingly, our results revealed that the development of the prodrugs can significantly enhance the anticancer potential of EPA. Finally, the drug uncaging process from the prodrugs by the intracellular esterases was studied in the cellular medium by measuring the turn-on fluorescence using fluorescence microscopy. Therefore, the present study highlights the rational development of the fluorogenic prodrugs of EPA, which will help enhance its anticancer potential with better therapeutic potential.

show abstract

Aldose reductase and cancer metabolism: The master regulator in the limelight

Cited by 5 publications

References 152 publications

Decoding selectivity: computational insights into AKR1B1 and AKR1B10 inhibition

Decoding selectivity: computational insights into AKR1B1 and AKR1B10 inhibition

Multi-target anticancer activity of compounds isolated from galls of Pistacia chinensis subsp. integerrima: A mechanistic investigation

Esterase-Responsive Fluorogenic Prodrugs of Aldose Reductase Inhibitor Epalrestat: An Innovative Strategy toward Enhanced Anticancer Activity

Contact Info

Product

Resources

About