Advanced prodrug strategies in nucleoside analogues targeting the treatment of gastrointestinal malignancies

Xu, Xing; Li, Zixuan; Yao, Xiaomei; Sun, Nannan; Chang, Junbiao

doi:10.3389/fcell.2023.1173432

Cited by 4 publications

(3 citation statements)

References 68 publications

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“…In principle, the oral delivery of 5-FU would eliminate the need for long infusion, however, the direct oral administration of 5-FU is not feasible due to its phosphorylation via OPRT, which promotes ribonucleotide-mediated GI toxicity. To overcome this limitation, 5-FU prodrugs that were orally available were developed [27], of which capecitabine is the most widely used clinically (Table 1). Capecitabine.…”

Section: Oral 5-fu Prodrugsmentioning

confidence: 99%

Review of Prodrug and Nanodelivery Strategies to Improve the Treatment of Colorectal Cancer with Fluoropyrimidine Drugs

Sarkar,

Kiren,

Gmeiner

2024

Pharmaceutics

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Fluoropyrimidine (FP) drugs are central components of combination chemotherapy regimens for the treatment of colorectal cancer (CRC). FP-based chemotherapy has improved survival outcomes over the last several decades with much of the therapeutic benefit derived from the optimization of dose and delivery. To provide further advances in therapeutic efficacy, next-generation prodrugs and nanodelivery systems for FPs are being developed. This review focuses on recent innovative nanodelivery approaches for FP drugs that display therapeutic promise. We summarize established, clinically useful FP prodrug strategies, including capecitabine, which exploit tumor-specific enzyme expression for optimal anticancer activity. We then describe the use of FP DNA-based polymers (e.g., CF10) for the delivery of activated FP nucleotides as a nanodelivery approach with proven activity in pre-clinical models and with clinical potential. Multiple nanodelivery systems for FP delivery show promise in CRC pre-clinical models and we review advances in albumin-mediated FP delivery, the development of mesoporous silica nanoparticles, emulsion-based nanoparticles, metal nanoparticles, hydrogel-based delivery, and liposomes and lipid nanoparticles that display particular promise for therapeutic development. Nanodelivery of FPs is anticipated to impact CRC treatment in the coming years and to improve survival for cancer patients.

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Section: Oral 5-fu Prodrugsmentioning

confidence: 99%

Review of Prodrug and Nanodelivery Strategies to Improve the Treatment of Colorectal Cancer with Fluoropyrimidine Drugs

Sarkar,

Kiren,

Gmeiner

2024

Pharmaceutics

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“…Prodrugs with an amide linkage to valproic acid, instead of ester linkages LY2334737 was designed by blocking the deamination site at the N4 position of gemcitabine Pancreatic specific cancer treatment [5] CP-4126 CP-4126 is a 5'-elaidic acid ester prodrug of gemcitabine CP-4126 is a transporter-independent analog of gemcitabine, entering cells primarily without hENT1…”

Section: Ly2334737mentioning

confidence: 99%

“…Gemcitabine-resistant pancreatic adenocarcinoma [5] NUC-1031 Anti-inflammatory and Anti-VEGF agent [11] Sulfasalazine Azo linkage which is reduced in colon by azo reductases enzyme secreted by colonic microflora. Colon specific prodrug of 5-ASA and Sulfapyridine.…”

Section: Ly2334737mentioning

confidence: 99%

Prodrug Rewards in Medicinal Chemistry: An Advance and Challenges Approach for Drug Designing

Husain,

Monga,

Narwal

et al. 2023

Chemistry & Biodiversity

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This article emphasizes the importance of prodrugs and their diverse spectrum of effects in the field of developing novel drugs for a variety of biological applications. Prodrugs are chemicals that are supplied inactively, but then go through enzymatic and chemical transformation in vivo to release the active parent medication that can have the desired pharmacological effect. By adding an inactive chemical moiety, prodrugs are improved in a number of ways that contribute to their potency and durability. For the purpose of illustrating the usefulness of the prodrug approach, this review covers examples of prodrugs that have been made available or are now undergoing human trials. Additionally, it included lists of the most common functional groups, carrier linkers, and reactive chemicals that can be used to create prodrugs. The current study also provides a brief introduction, several chemical methods and modifications for creating prodrugs and mutual prodrugs, as well as an explanation of recent advancements and difficulties in the field of prodrug design. The primary chemical carriers employed in the creation of prodrugs, such as esters, amides, imides, NH‐acidic carriers, amines, alcohols, carbonyl, carboxylic, and azo‐linkages, are also discussed. This review also discusses glycosidic and triglyceride mutually activated prodrugs, which aim to deliver the drugs after bioconversion at the intended site of action. The article also discusses the extensive chemistry and wide variety of applications of recently approved prodrugs, such as antibacterial, anti‐inflammatory, cardiovascular, antiplatelet, antihypertensive, atherosclerotic, antiviral, etc. In order to illustrate the prodrug and mutual drug concept's various applications and highlight its many triumphs in overcoming the formulation and delivery of problematic pharmaceuticals, this work represents a thorough guide that includes the synthetic moiety for the reader.

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Is it still worth renewing nucleoside anticancer drugs nowadays?

Liu

2024

European Journal of Medicinal Chemistry

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Advanced prodrug strategies in nucleoside analogues targeting the treatment of gastrointestinal malignancies

Cited by 4 publications

References 68 publications

Review of Prodrug and Nanodelivery Strategies to Improve the Treatment of Colorectal Cancer with Fluoropyrimidine Drugs

Review of Prodrug and Nanodelivery Strategies to Improve the Treatment of Colorectal Cancer with Fluoropyrimidine Drugs

Prodrug Rewards in Medicinal Chemistry: An Advance and Challenges Approach for Drug Designing

Is it still worth renewing nucleoside anticancer drugs nowadays?

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