Preparation and Bioactivity Assessment of Chitosan-1-Acetic Acid-5-Flurouracil Conjugates as Cancer Prodrugs

Mohammed, Mohsin O.; Hussain, Kameran S.; Haj, Nadia Q.

doi:10.3390/molecules22111629

Cited by 17 publications

(9 citation statements)

References 27 publications

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“…17 , 18 Its molecular structure is similar to that of cellulose except for the presence of a primary amino group in the C2 position of the anhydroglucose unit. 19 This structural similarity allows blending cellulose and chitosan into a homogeneous matrix. These properties make chitosan an attractive doping agent to increase the yield of the cellulose-based CF precursor filaments without significant impairment of the mechanical property.…”

Section: Introductionmentioning

confidence: 99%

Close Packing of Cellulose and Chitosan in Regenerated Cellulose Fibers Improves Carbon Yield and Structural Properties of Respective Carbon Fibers

et al. 2020

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A low carbon yield is a major limitation for the use of cellulose-based filaments as carbon fiber precursors. The present study aims to investigate the use of an abundant biopolymer chitosan as a natural charring agent particularly on enhancing the carbon yield of the cellulose-derived carbon fiber. The ionic liquid 1,5-diazabicyclo[4.3.0]non-5-enium acetate ([DBNH]OAc) was used for direct dissolution of cellulose and chitosan and to spin cellulose–chitosan composite fibers through a dry-jet wet spinning process (Ioncell). The homogenous distribution and tight packing of cellulose and chitosan revealed by X-ray scattering experiments enable a synergistic interaction between the two polymers during the pyrolysis reaction, resulting in a substantial increase of the carbon yield and preservation of mechanical properties of cellulose fiber compared to other cobiopolymers such as lignin and xylan.

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Section: Introductionmentioning

confidence: 99%

Close Packing of Cellulose and Chitosan in Regenerated Cellulose Fibers Improves Carbon Yield and Structural Properties of Respective Carbon Fibers

et al. 2020

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“…Studies on other molecules, such as the novel organic nitrate RS-7897, have shown that hydrolysis of an amide bond can release more active molecules than the parent molecule 25. Furthermore, amide bonds are often incorporated into drug designs, as a linker to tether a drug to a targeting peptide 26.…”

Section: Introductionmentioning

confidence: 99%

Kartogenin hydrolysis product 4-aminobiphenyl distributes to cartilage and mediates cartilage regeneration

Zhang¹,

Hu²,

Liu³

et al. 2019

Theranostics

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Rationale The small molecule Kartogenin (KGN) promotes cartilage regeneration in osteoarthritis (OA) by activating stem cells differentiation, but its pharmacological mode-of-action remains unclear. KGN can be cleaved into 4-aminobiphenyl (4-ABP) and phthalic acid (PA) following enzymolysis of an amide bond. Therefore, this study investigated whether 4-ABP or PA exerted the same action as KGN.Methods KGN, 4-ABP and PA were analyzed in cartilage of mice after oral, intravenous or intra-articular administration of KGN by liquid chromatography-mass spectrometry method. Their effect on proliferation and chondrogenic differentiation of mesenchymal stem cells (MSC) was evaluated in vitro. Furthermore, their effect on cartilage preservation was tested in mice OA model induced by destabilization of medial meniscus. OA severity was quantified using OARSI histological scoring. Transcriptional analysis was used to find the possible targets of the chemicals, which were further validated.Results We demonstrated that while oral or intra-articular KGN delivery effectively ameliorated OA phenotypes in mice, only 4-ABP was detectable in cartilage. 4-ABP could induce chondrogenic differentiation and proliferation of MSC in vitro and promote cartilage repair in OA mouse models mainly by increasing the number of CD44+/CD105+ stem-cell and prevention of matrix loss. These effect of 4-ABP was stronger than that of KGN. Transcriptional profiling of 4-ABP-stimulated MSC suggested that RPS6KA2 and the PI3K-Akt pathway were 4-ABP targets; 4-ABP could activate the PI3K-Akt pathway to promote MSC proliferation and repair OA injury, which was blocked in RPS6KA2-knockdown MSC or RPS6KA2-deficient mice.Conclusion 4-ABP bio-distribution in cartilage promotes proliferation and chondrogenic differentiation of MSC, and repairs osteoarthritic lesions via PI3K-Akt pathway activation.

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“…Then 4 h later, the solution on the plate was removed and the content was dissolved with DMSO [33]. The absorption was measured at 490 nm and cell viability was calculated, cell viability% = OD of treated cells/OD of untreated cells × 100% [51].…”

Section: Methodsmentioning

confidence: 99%

Synthesis, Biological Evaluation and Low-Toxic Formulation Development of Glycosylated Paclitaxel Prodrugs

et al. 2018

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Paclitaxel (PTX) is a famous anti-cancer drug with poor aqueous solubility. In clinical practices, Cremophor EL (polyethoxylated castor oil), a toxic surfactant, is used for dissolution of PTX, which accounts for serious side effects. In the present study, a single glucose-conjugated PTX prodrug (SG-PTX) and a double glucose-conjugated PTX prodrug (DG-PTX) were synthesized with a glycosylated strategy via succinate linkers. Both of the two prodrugs presented significant solubility improvement and drug-like lipophilicities. Compared to DG-PTX, SG-PTX manifested more promising release of the parent drug in serum. A high percentage of PTX released from SG-PTX could be detected after enzymatic hydrolysis of β-glucuronidase. Besides, both of the two prodrugs exhibited effective cytotoxicity against breast cancer cells and ovarian cancer cells, but presented reduced cytotoxicity against normal breast cells. Moreover, SG-PTX manifested impressive solubility in a low toxic formulation (without ethanol) with a different percentage of Cremophor EL. These results indicated that glycosylation is a promising strategy for PTX modification and SG-PTX may be a feasible and potential type of PTX prodrug. In addition, ethanol-free formulation with a low percentage of Cremophor EL might have the potential to develop a safer formulation for further studies of glycosylated PTX prodrugs.

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Preparation and Bioactivity Assessment of Chitosan-1-Acetic Acid-5-Flurouracil Conjugates as Cancer Prodrugs

Cited by 17 publications

References 27 publications

Close Packing of Cellulose and Chitosan in Regenerated Cellulose Fibers Improves Carbon Yield and Structural Properties of Respective Carbon Fibers

Close Packing of Cellulose and Chitosan in Regenerated Cellulose Fibers Improves Carbon Yield and Structural Properties of Respective Carbon Fibers

Kartogenin hydrolysis product 4-aminobiphenyl distributes to cartilage and mediates cartilage regeneration

Synthesis, Biological Evaluation and Low-Toxic Formulation Development of Glycosylated Paclitaxel Prodrugs

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