Pegylation of phenothiazine – A synthetic route towards potent anticancer drugs

Cibotaru, Sandu; Nastasa, Valentin; Sandu, Andreea-Isabela; Bostănaru, Andra-Cristina; Mareș, Mihai; Marin, Luminița

doi:10.1016/j.jare.2021.07.003

Cited by 16 publications

(4 citation statements)

References 51 publications

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“…The investigation of phenothiazine derivatives as antitumor agents revealed inhibition of the farnesyltransferase(FT) enzyme as an important factor of the antitumor mechanism [ 30 ], based on the binding of its thiol units and the coordination of Zn 2+ or Mg 2+ sites [ 29 , 31 ]. To estimate the ability of the studied compounds to inhibit the FT, their ability to bind the Zn 2+ or Mg 2+ ions was investigated by incubation in similar conditions as in vitro antitumor tests.…”

Section: Resultsmentioning

confidence: 99%

“…70% being reported [ 28 ]. Their deeper investigation brought into researcher attention another potential anticancer mechanism, that is, inhibition of enzymes with a key role in tumor cell proliferation, such as farnesyltransferase [ 26 , 29 , 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

“…This literature survey, cumulated with our own research in the phenothiazine field [ 29 , 40 , 41 , 42 ], encouraged us to design new structures of antitumor drugs based on phenothiazine, PEG and sulfonamide units. Imine bond, known for its reversible formation leading to dynamic systems prone to respond under external stimuli [ 43 , 44 , 45 ], was used as a linking unit ( Scheme 1 ).…”

Section: Introductionmentioning

confidence: 99%

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Antitumor Activity of PEGylated and TEGylated Phenothiazine Derivatives: Structure–Activity Relationship

Cibotaru¹,

Sandu²,

Nicolescu³

et al. 2023

IJMS

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The paper aims to investigate the antitumor activity of a series of phenothiazine derivatives in order to establish a structure–antitumor activity relationship. To this end, PEGylated and TEGylated phenothiazine have been functionalized with formyl units and further with sulfonamide units via dynamic imine bonds. Their antitumor activity was monitored in vitro against seven human tumors cell lines and a mouse one compared to a human normal cell line by MTS assay. In order to find the potential influence of different building blocks on antitumor activity, the antioxidant activity, the ability to inhibit farnesyltransferase and the capacity to bind amino acids relevant for tumor cell growth were investigated as well. It was established that different building blocks conferred different functionalities, inducing specific antitumor activity against the tumor cells.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antitumor Activity of PEGylated and TEGylated Phenothiazine Derivatives: Structure–Activity Relationship

Cibotaru¹,

Sandu²,

Nicolescu³

et al. 2023

IJMS

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“…These ions then react with excess PA, leading to the formation of insoluble Zn‐PA complexes (Reaction II). [ 48 ] Additionally, the dissociation of water is an inevitable occurrence in aqueous solutions, leading to the formation of H + and OH − ions (Reaction III). [ 49 ] According to the detection of zinc carbonate in the XPS data, reaction IV is simulated.…”

Section: Resultsmentioning

confidence: 99%

Controllable Solid Electrolyte Interphase by Ionic Environment Regulation for Stable Zn‐Ion Battery

Liu,

Li,

Zhang

et al. 2023

Small

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Artificial solid electrolyte interphase in organic solutions is effective and facile for long‐cycling aqueous zinc ion batteries. However, the specific effects on different ionic environments have not been thoroughly investigated. Herein, pyromellitic acid (PA) are employed as organic ligand to coordinate with Zn2+ under various ionic environments. The connection between the ionic environment and reaction spontaneity is analyzed to provide insights into the reasons behind the effectiveness of the SEI layer and to characterize its protective impact on the zinc anode. Notably, the PA solution (pH4) lacking OH− contributes to the formation of a dense and ultrathin SEI with Zn‐PA coordination, preventing direct contact between the anode and electrolyte. Moreover, the presence of organic functional groups facilitates a uniform flux of Zn2+. These advantages enable stable cycling of the PA4‐Zn symmetric cell at a current density of 3 mA cm−2 for over 3500 h. The PA4‐Zn//MVO full cell demonstrates excellent electrochemical reversibility. Investigating the influence of the ionic environment on SEI generation informs the development of novel SEI strategies.

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Synthesis of new phenothiazine derivatives: Molecular docking, assessment of cytotoxic activity and oxidant–antioxidant properties on PCS‐201‐012, HT‐29, and SH‐SY5Y cell lines

Tan,

Kartal,

Yesilyurt

et al. 2024

Archiv der Pharmazie

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Phenothiazine (PTZ) derivatives have been acknowledged as versatile compounds with significant implications across various areas of medicine, particularly, in cancer research. The cytotoxic effects of synthesized compounds on both normal and cancerous cells, along with their oxidant–antioxidant properties, are pivotal factors in cancer treatment strategies. In the current study, eight new PTZ derivatives were synthesized and the compounds' cytotoxic activities were assessed by 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide (MTT) assay while the oxidant–antioxidant properties were evaluated by oxidative stress index (OSI) calculation in SH‐SY5Y (a human neuroblastoma cell line), HT‐29 (a human colorectal adenocarcinoma cell line), and PCS‐201‐012 (a human primary dermal fibroblast cell line) cells. Consequently, the half‐maximal inhibitory concentration (IC50) values of compound 3a were determined to be 218.72, 202.85, and 227.86 μM while the IC50 values of compound 3b were defined to be 227.42, 199.27, and 250.11 μM in PCS‐201‐012, HT‐29, and SH‐SY5Y cells, respectively. Additionally, it was determined that the synthesized compounds demonstrated the lowest OSI in PCS‐201‐012 cells as compared to the other cell lines.

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Pegylation of phenothiazine – A synthetic route towards potent anticancer drugs

Cited by 16 publications

References 51 publications

Antitumor Activity of PEGylated and TEGylated Phenothiazine Derivatives: Structure–Activity Relationship

Antitumor Activity of PEGylated and TEGylated Phenothiazine Derivatives: Structure–Activity Relationship

Controllable Solid Electrolyte Interphase by Ionic Environment Regulation for Stable Zn‐Ion Battery

Synthesis of new phenothiazine derivatives: Molecular docking, assessment of cytotoxic activity and oxidant–antioxidant properties on PCS‐201‐012, HT‐29, and SH‐SY5Y cell lines

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