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Pegylation of phenothiazine - A synthetic route towards potent anticancer drugs

Show simple item record Cibotaru, Sandu Năstasă, Valentin Sandu, Andreea-Isabela Bostănaru, Andra-Cristina Mareș, Mihai Marin, Luminița 2023-03-17T16:25:14Z 2023-03-17T16:25:14Z 2021-07-09
dc.identifier.citation Cibotaru, Sandu, Valentin Năstasă, Andreea-Isabela Sandu, Andra-Cristina Bostanaru, Mihai Mareș, Luminița Marin. 2021. ”Pegylation of phenothiazine - A synthetic route towards potent anticancer drugs”. Journal of Advanced Research 37: 279-290. en_US
dc.identifier.issn 2090-1232
dc.description.abstract Introduction: Cancer is a big challenge of the 21 century, whose defeat requires efficient antitumor drugs. Objectives: The paper aims to investigate the synergistic effect of two structural building blocks, phenothiazine and poly(ethylene glycol), towards efficient antitumor drugs. Methods: Two PEGylated phenothiazine derivatives were synthetized by attaching poly(ethylene glycol) of 550 Da to the nitrogen atom of phenothiazine by ether or ester linkage. Their antitumor activity has been investigated on five human tumour lines and a mouse tumor line as well, by determination of IC50. The in vivo toxicity was determined by measuring the LD50 in BALB/c mice by the sequential method and the in vivo antitumor potential was measured by the tumours growth test. The antitumor mechanism was investigated by complexation studies of zinc and magnesium ions characteristic to the farnesyltransferase enzyme, by studies of self-aggregation in the cells proximity and by investigation of the antitumor properties of the acid species resulted by enzymatic cleavage of the PEGylated derivatives. Results: The two compounds showed antitumor activity, with IC50 against mouse colon carcinoma cell line comparable with that of the traditional antitumor drugs 5-Fluorouracil and doxorubicin. The phenothiazine PEGylation resulted in a significant toxicity diminishing, the LD50 in BALB/c mice increasing from 952.38 up to 1450 mg/kg, in phenothiazine equivalents. Both compounds inflicted a 92% inhibition of the tumour growth for doses much smaller than LD50. The investigation of the possible tumour inhibition mechanism suggested the nanoaggregate formation and the cleavage of ester bonds as key factors for the inhibition of cancer cell proliferation and biocompatibility improvement. Conclusion: Phenothiazine and PEG building blocks have a synergetic effect working for both tumour growth inhibition and biocompatibility improvement. All these findings recommend the PEGylated phenothiazine derivatives as a valuable workbench for a next generation of antitumor drugs. en_US
dc.language.iso en en_US
dc.publisher Elsevier B.V. on behalf of Cairo University en_US
dc.rights Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
dc.subject phenothiazine en_US
dc.subject poly(ethylene glycol) en_US
dc.subject Tumour growth inhibition en_US
dc.title Pegylation of phenothiazine - A synthetic route towards potent anticancer drugs en_US
dc.type Article en_US Sandu Cibotaru, Andreea-Isabela Sandu, Luminița Marin, Petru Poni” Institute of Macromolecular Chemistry of Romanian Academy, Iași, Romania Valentin Năstasă, Andra-Cristina Bostanaru, Mihai Mareș, Ion Ionescu de la Brad” University, Laboratory of Antimicrobial Chemotherapy, Iași, Romania
dc.publicationName Journal of Advanced Research
dc.volume 37
dc.publicationDate 2021
dc.startingPage 279
dc.endingPage 290
dc.identifier.doi 10.1016/j.jare.2021.07.003

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Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)