Synthesis and antiproliferative activities of doxorubicin thiol conjugates and doxorubicin-SS-cyclic peptide

Darwish, Shaban; Sadeghiani, N.; Fong, Shirley S.M.; Mozaffari, Saghar; Hamidi, Parinaz; Withana, Thimanthi; Yang, Sun; Tiwari, Rakesh; Parang, Keykavous

doi:10.1016/j.ejmech.2018.10.042

Cited by 33 publications

(20 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whereas, the concentration of GSH in the tumor tissue is 4 times higher than that of the normal tissues [40]. Darwish et al [41] have previously reported the impact of a disulfide bridge in increasing the cytotoxic activity of Dox conjugated to [C(WR) 4 K] when investigated in HEK-293, HT-1080, and SKOV-3 cells as compared to Dox after 72 h incubation. The mechanism affording the thiol-containing CPT followed by the carbonate bond cleavage liberating thiazolidinone and CPT and five-membered thiolactam was demonstrated by Henne et al and Zhang et al [39,40].…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Antiproliferative Activities of Conjugates of Paclitaxel and Camptothecin with a Cyclic Cell-Penetrating Peptide

et al. 2019

Self Cite

View full text Add to dashboard Cite

Cell-penetrating peptide [WR]5 has been previously shown to be an efficient molecular transporter for various hydrophilic and hydrophobic molecules. The peptide was synthesized using Fmoc/tBu solid-phase chemistry, and one arginine was replaced with one lysine to enable the conjugation with the anticancer drugs. Paclitaxel (PTX) was functionalized with an esterification reaction at the C2′ hydroxyl group of PTX with glutaric anhydride and conjugated with the cyclic peptide [W(WR)4K(βAla)] in DMF to obtain the peptide-drug conjugate PTX1. Furthermore, camptothecin (CPT) was modified at the C(20)-hydroxyl group through the reaction with triphosgene. Then, it was conjugated with two functionalized cyclic peptides through a formyl linker affording two different conjugates, namely CPT1 and CPT2. All the conjugates showed better water solubility as compared to the parent drug. The cytotoxicity assay of the drugs and their conjugates with the peptides were evaluated in the human breast cancer MCF-7 cell line. PTX inhibited cell proliferation by 39% while the PTX-peptide conjugate inhibited the proliferation by ~18% after 72 h incubation. On the other hand, CPT, CPT1, and CPT2 reduced the cell proliferation by 68%, 39%, and 62%, respectively, in the MCF-7 cell lines at 5 µM concentration after 72 h incubation.

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis and Antiproliferative Activities of Conjugates of Paclitaxel and Camptothecin with a Cyclic Cell-Penetrating Peptide

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…We have reported the application of cyclic CPPs containing alternatively positively charged arginine and hydrophobic tryptophan residues, [WR] 4 and [WR] 5 , as drug delivery tools and nuclear targeting tools in 2011 [209]. Several other monocyclic CPPs were engineered based on this template and were shown to be efficient molecular transporters for enhancing the efficacy of existing chemotherapeutic, antiviral, and antibacterial agents [210][211][212][213][214][215][216][217][218][219]. The monocyclic CPPs containing tryptophan and arginine residues were also used to conjugate with potential therapeutic agents.…”

Section: Peptide-based Therapies 71 Monocyclic Bicyclic and Tricyclic Cell-penetrating Peptides As Molecular Transportersmentioning

confidence: 99%

“…The monocyclic CPPs containing tryptophan and arginine residues were also used to conjugate with potential therapeutic agents. For instance, monocyclic peptides were conjugated with doxorubicin, paclitaxel, and camptothecin [216,220] demonstrating localization of the drug moiety in the nucleus in case of doxorubicin. Adding to the previous work, we also demonstrated that several monocyclic peptides containing cysteine and arginine residues, such as cyclic [CR] 4 , significantly enhanced the cellular uptake of a cell-impermeable phosphopeptide (F')-Gly-(pTyr)-Glu-Glu-Ile (F'-GpYEEI) in the presence of endocytic inhibitors and sodium azide in the lymphoblastic leukemia cell line (CCRF-CEM) [218].…”

Section: Peptide-based Therapies 71 Monocyclic Bicyclic and Tricyclic Cell-penetrating Peptides As Molecular Transportersmentioning

confidence: 99%

A Global Review on Short Peptides: Frontiers and Perspectives

et al. 2021

Self Cite

View full text Add to dashboard Cite

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide “drugs” initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.

show abstract

“…The disulfide bridge is expected to increase the activity of the conjugate inside cancer cells because it can be cleaved with intracellular thiol, such as glutathione, which is more active in cancer cells compared to normal cells. Indeed, their results demonstrate an enhance cytotoxic effect of the conjugate towards cancer cells compared to the drug alone, with a limited toxicity [139].…”

Section: Cpp-based Anti-cancer Therapy Optimizationmentioning

confidence: 99%

Recent Advances in Cell Penetrating Peptide-Based Anticancer Therapies

2019

View full text Add to dashboard Cite

Cell-penetrating-peptides (CPPs) are small amino-acid sequences characterized by their ability to cross cellular membranes. They can transport various bioactive cargos inside cells including nucleic acids, large proteins, and other chemical compounds. Since 1988, natural and synthetic CPPs have been developed for applications ranging from fundamental to applied biology (cell imaging, gene editing, therapeutics delivery). In recent years, a great number of studies reported the potential of CPPs as carriers for the treatment of various diseases. Apart from a good efficacy due to a rapid and potent delivery, a crucial advantage of CPP-based therapies is the peptides low toxicity compared to most drug carriers. On the other hand, they are quite unstable and lack specificity. Higher specificity can be obtained using a cell-specific CPP to transport the therapeutic agent or using a non-specific CPP to transport a cargo with a targeted activity. CPP-cargo complexes can also be conjugated to another moiety that brings cell- or tissue-specificity. Studies based on all these approaches are showing promising results. Here, we focus on recent advances in the potential usage of CPPs in the context of cancer therapy, with a particular interest in CPP-mediated delivery of anti-tumoral proteins.

show abstract

Synthesis and antiproliferative activities of doxorubicin thiol conjugates and doxorubicin-SS-cyclic peptide

Cited by 33 publications

References 51 publications

Synthesis and Antiproliferative Activities of Conjugates of Paclitaxel and Camptothecin with a Cyclic Cell-Penetrating Peptide

Synthesis and Antiproliferative Activities of Conjugates of Paclitaxel and Camptothecin with a Cyclic Cell-Penetrating Peptide

A Global Review on Short Peptides: Frontiers and Perspectives

Recent Advances in Cell Penetrating Peptide-Based Anticancer Therapies

Contact Info

Product

Resources

About