Application of Mono‐ and Disaccharides in Drug Targeting and Efficacy

Yuan, Si; Li, Mao L.; Chen, Jian S.; Zhou, Li; Zhou, Wen

doi:10.1002/cmdc.201700762

Cited by 33 publications

(22 citation statements)

References 149 publications

(364 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…D-galactose, together with D-glucose, are actively transported across the blood-brain barrier (BBB), making these hexoses highly attractive for the specific delivery of drugs to the brain 92 . Galactose-conjugated dopamine was found to have better BBB permeability, bioavailability, and therapeutic effects against Parkinson’s disease 93 – 95 . Finally, galactose is a preferred glycan candidate for targeting hIAPP because, due to hepatic metabolism, insulin and glucose level responses to galactose are lower than for glucose 96 , 97 .…”

Section: Discussionmentioning

confidence: 99%

Tryptophan-galactosylamine conjugates inhibit and disaggregate amyloid fibrils of Aβ42 and hIAPP peptides while reducing their toxicity

et al. 2020

View full text Add to dashboard Cite

Self-assembly of proteins into amyloid fibrils is a hallmark of various diseases, including Alzheimer's disease (AD) and Type-2 diabetes Mellitus (T2DM). Aggregation of specific peptides, like Aβ42 in AD and hIAPP in T2DM, causes cellular dysfunction resulting in the respective pathology. While these amyloidogenic proteins lack sequence homology, they all contain aromatic amino acids in their hydrophobic core that play a major role in their selfassembly. Targeting these aromatic residues by small molecules may be an attractive approach for inhibiting amyloid aggregation. Here, various biochemical and biophysical techniques revealed that a panel of tryptophan-galactosylamine conjugates significantly inhibit fibril formation of Aβ42 and hIAPP, and disassemble their pre-formed fibrils in a dosedependent manner. They are also not toxic to mammalian cells and can reduce the cytotoxicity induced by Aβ42 and hIAPP aggregates. These tryptophan-galactosylamine conjugates can therefore serve as a scaffold for the development of therapeutics towards AD and T2DM.

show abstract

Section: Discussionmentioning

confidence: 99%

Tryptophan-galactosylamine conjugates inhibit and disaggregate amyloid fibrils of Aβ42 and hIAPP peptides while reducing their toxicity

et al. 2020

View full text Add to dashboard Cite

show abstract

“…For examples, several CFA esters have reported to have antitumor, plant growth inhibitory, insecticidal, and miticidal, antibiotic, and antifriction property [ [8] , [9] , [10] , [11] , [12] ]. Therefore, CFA esters have long been used as versatile intermediates in the syntheses of many natural products due to the presence of multifunctional groups [ [13] , [14] , [15] ], in addition to their extensive use for design, and development of new drugs [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Novel mannopyranoside esters as sterol 14α-demethylase inhibitors: Synthesis, PASS predication, molecular docking, and pharmacokinetic studies

Matin

Chakraborty

Alam

et al. 2020

Carbohydrate Research

View full text Add to dashboard Cite

Direct unimolar one-step valeroylation of methyl α- d -mannopyranoside (MDM) furnished mainly 6- O -valeroate. However, similar reaction catalyzed by DMAP resulted 3,6-di- O -valeroate (21%) and 6- O -valeroate (47%) indicating reactivity sequence as 6-OH>3-OH>2-OH,4-OH. To get potential antimicrobial agents, 6- O -valeroate was converted into four 2,3,4-di- O -acyl esters, and 3,6-di- O -valeroate was converted into 2,4-di- O -acetate. Direct tetra- O -valeroylation of MDM gave a mixture of 2,3,4,6-tetra- O -valeroate and 2,3,6-tri- O -valeroate indicating that the C2–OH is more reactive than the equatorial C4–OH. The activity spectra analysis along with in vitro antimicrobial evaluation clearly indicated that these novel MDM esters had better antifungal activities over antibacterial agents. In this connection, molecular docking indicated that these MDM esters acted as competitive inhibitors of sterol 14α-demethylase (CYP51), an essential enzyme for clinical target to cure several infectious diseases. Furthermore, pharmacokinetic studies revealed that these MDM esters may be worth considering as potent candidates for oral and topical administration. Structure activity relationship (SAR) affirmed that saturated valeric chain (C5) in combination with caprylic (C8) chains was more promising CYP51 inhibitor over conventional antifungal antibiotics.

show abstract

“…As carbohydrates are involved in tumor development, progression, invasion and metastasis, glycan structural abnormalities were always considered as golden bio-marks to diagnose and rank cancer status 23 , so carbohydrates including mono- or disaccharides were incorporated to non-specific antitumor molecules in order to improve the targeting and efficacy properties. The disaccharide moiety of bleomycin (BLM), composed of 3- O -carbamoyl-D-mannose and L-gulose, was employed to improve targeting of tumor cells is one of the recently employed strategies 24 .…”

Section: Introductionmentioning

confidence: 99%

Disaccharides obtained from carrageenans as potential antitumor agents

Calvo

Stortz

Sáenz

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Carrageenans are sulfated galactans found in certain red seaweeds with proven biological activities. In this work, we have prepared purified native and degraded κ-, ι-; and λ-carrageenans, including the disaccharides (carrabioses) and disaccharide-alditols (carrabiitols) from seaweed extracts as potential antitumor compounds and identified the active principle of the cytotoxic and potential antitumor properties of these compounds. Both κ and ι-carrageenan, as well as carrageenan oligosaccharides showed cytotoxic effect over LM2 tumor cells. Characterized disaccharides (carrabioses) and the reduced product carrabiitols, were also tested. Only carrabioses were cytotoxic, and among them, κ-carrabiose was the most effective, showing high cytotoxic properties, killing the cells through an apoptotic pathway. In addition, the cells surviving treatment with κ-carrabiose, showed a decreased metastatic ability in vitro , together with a decreased cell-cell and cell-matrix interactions, thus suggesting possible antitumor potential. Overall, our results indicate that most cytotoxic compounds derived from carrageenans have lower molecular weights and sulfate content. Potential applications of the results emerging from the present work include the use of disaccharide units such as carrabioses coupled to antineoplasics in order to improve its cytotoxicity and antimetastatic properties, and the use of ι-carrageenan as adjuvant or carrier in anticancer treatments.

show abstract

Application of Mono‐ and Disaccharides in Drug Targeting and Efficacy

Cited by 33 publications

References 149 publications

Tryptophan-galactosylamine conjugates inhibit and disaggregate amyloid fibrils of Aβ42 and hIAPP peptides while reducing their toxicity

Tryptophan-galactosylamine conjugates inhibit and disaggregate amyloid fibrils of Aβ42 and hIAPP peptides while reducing their toxicity

Novel mannopyranoside esters as sterol 14α-demethylase inhibitors: Synthesis, PASS predication, molecular docking, and pharmacokinetic studies

Disaccharides obtained from carrageenans as potential antitumor agents

Contact Info

Product

Resources

About