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Current Bioactive Compounds


ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Research Article

Investigation of Antiblastic and Antibacterial Properties of Binuclear Platinum (II)-Interferon Conjugate

Author(s): Evgenii Plotnikov* and Vladimir Plotnikov

Volume 18, Issue 7, 2022

Published on: 10 February, 2022

Article ID: e120122200174 Pages: 4

DOI: 10.2174/1573407218666220112112008

Price: $65


Introduction: This work aimed to create a new platinum-interferon conjugate and investigate its properties.

Background: Multiple drug resistance of tumor cells is a serious challenge in modern medicine. Neoplastic diseases are often complicated by persistent bacterial infections, which impairs efficacy and the outcome of anticancer therapy. The development of new bifunctional drugs for the treatment of tumor growth and bacterial complications is an urgent task.

Objective: The objective of this study was to evaluate the complex antiblastic and antibacterial properties of interferon-platinum conjugate in vitro.

Materials and Methods: The coordination complex of dichloro-N,N,N,N-tetrakis-(2-aminoethyl)- 1,6-hexamethylenediaminobisplatin dichloride was used for production of conjugate with human α-interferon. The binding of a metal complex with protein was established by means of radiochemical neutron activation analysis. As test objects, we used lympholeukemic Jurkat cells line, human lymphocytes in reaction of lymphocyte blastic transformation and different strains of microorganisms, including Staphylococcus aureus and Pseudomonas aeruginosa.

Results: Binuclear platinum human α-interferon conjugate has a significant dose-dependent antibacterial and antiproliferative suppressive effect on target cells and bacteria.

Conclusion: The tested preparation can be of a certain interest in drug designing for rational antiblastic therapy, especially in the case of infectious complications. This conjugate can be a convenient platform for creating drugs for the complex therapy of oncological diseases with bacterial complications.

Keywords: Interferon, platinum, metalloprotein conjugate, Jurkat cell, Staphylococcus aureus, Pseudomonas aeruginosa.

Graphical Abstract
Qi, R.; Wang, Y.; Bruno, P.M.; Xiao, H.; Yu, Y.; Li, T.; Lauffer, S.; Wei, W.; Chen, Q.; Kang, X.; Song, H.; Yang, X.; Huang, X.; Detappe, A.; Matulonis, U.; Pepin, D.; Hemann, M.T.; Birrer, M.J.; Ghoroghchian, P.P. Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer. Nat. Commun., 2017, 8(1), 2166.
[] [PMID: 29255160]
Smith, K.F.; Goldberg, M.; Rosenthal, S.; Carlson, L.; Chen, J.; Chen, C.; Ramachandran, S. Global rise in human infectious disease outbreaks. J. R. Soc. Interface, 2014, 11(101), 20140950.
[] [PMID: 25401184]
Patel, C.; Acharya, S.; Patel, P. Antimicrobial adjuvants - A novel approach to manage antimicrobial resistance. Antiinfect. Agents, 2020, 18(4), 315-325.
Schechter, B.; Pauzner, R.; Arnon, R.; Haimovich, J.; Wilchek, M. Selective cytotoxicity against tumor cells by cisplatin complexed to antitumor antibodies via carboxymethyl dextran. Cancer Immunol. Immunother., 1987, 25(3), 225-230.
[] [PMID: 2445485]
Plotnikov, V.M. Cytotoxic Effect of Binar Cisplatin Immunoconjugate. In: Gene Therapy of Cancer. Advances in Experimental Medicine and Biology; Walden, P.; Trefzer, U.; Sterry, W.; Farzaneh, F.; Zambon, P., Eds.; Springer: Boston, MA, 1998; Vol. 451, pp. 151-152.
Abotaleb, M.; Kubatka, P.; Caprnda, M.; Varghese, E.; Zolakova, B.; Zubor, P.; Opatrilova, R.; Kruzliak, P.; Stefanicka, P.; Büsselberg, D. Chemotherapeutic agents for the treatment of metastatic breast cancer: An update. Biomed. Pharmacother., 2018, 101, 458-477.
[] [PMID: 29501768]
Conibear, A.C.; Hager, S.; Mayr, J.; Klose, M.H.M.; Keppler, B.K.; Kowol, C.R.; Heffeter, P.; Becker, C.F.W. Multifunctional αvβ6 integrin-specific peptide-Pt(IV) conjugates for cancer cell targeting. Bioconjug. Chem., 2017, 28(9), 2429-2439.
[] [PMID: 28796473]
Frejd, F.Y.; Kim, K.T. Affibody molecules as engineered protein drugs. Exp. Mol. Med., 2017, 49(3), e306.
[] [PMID: 28336959]
Vazquez-Lombardi, R.; Phan, T.G.; Zimmermann, C.; Lowe, D.; Jermutus, L.; Christ, D. Challenges and opportunities for non-antibody scaffold drugs. Drug Discov. Today, 2015, 20(10), 1271-1283.
[] [PMID: 26360055]
Plückthun, A. Designed ankyrin repeat proteins (DARPins): Binding proteins for research, diagnostics, and therapy. Annu. Rev. Pharmacol. Toxicol., 2015, 55, 489-511.
[] [PMID: 25562645]
Cánepa, C.; Imperiale, J.C.; Berini, C.A.; Lewicki, M.; Sosnik, A.; Biglione, M.M. Development of a drug delivery system based on chitosan nanoparticles for oral administration of Interferon-α. Biomacromolecules, 2017, 18(10), 3302-3309.
[] [PMID: 28837330]
Podobnik, B.; Helk, B.; Smilović, V.; Škrajnar, Š.; Fidler, K.; Jevševar, S.; Godwin, A.; Williams, P. Conjugation of PolyPEG to interferon alpha extends serum half-life while maintaining low viscosity of the conjugate. Bioconjug. Chem., 2015, 26(3), 452-459.
[] [PMID: 25629733]
Ozzello, L.; Blank, E.W.; De Rosa, C.M.; Ceriani, R.L.; Tölö, H.; Kauppinen, H-L.; Cantell, K. Conjugation of interferon alpha to a humanized monoclonal antibody (HuBrE-3vl) enhances the selective localization and antitumor effects of interferon in breast cancer xenografts. Breast Cancer Res. Treat., 1998, 48(2), 135-147.
[] [PMID: 9596485]
Yang, J-A.; Park, K.; Jung, H.; Kim, H.; Hong, S.W.; Yoon, S.K.; Hahn, S.K. Target specific hyaluronic acid-interferon alpha conjugate for the treatment of hepatitis C virus infection. Biomaterials, 2011, 32(33), 8722-8729.
[] [PMID: 21872329]
Nagyal, L.; Kumar, A.; Sharma, R.; Yadav, R.; Chaudhary, P.; Singh, R. Bioinorganic chemistry of platinum(IV) complexes as platforms for anticancer agents. Curr. Bioact. Compd., 2020, 16, 726-737.
Vlasov, V.V.; Kazakov, S.A.; Misovets, V.G. Synthesis of binuclear Pt (II) compounds with dichloro-N, N, N, N-tetrakis- (2-aminoethyl) -1,6-hexamethylenediaminobisplatin dichloride. Proc. U.S.S.R. Acad. Sci. (Atmos. Ocean. Phys.), 1982, 266(4), 866-870.
Plotnikov, V.M.; Kazakov, S.A.; Merkulov, V.G. Immunobiological activity of coordination platinum (II) compounds in complex with immunoglobulin fragments. Bull. Exp. Biol. Med., 1989, 9, 313-315.
Maillard, J.Y.; Hartemann, P. Silver as an antimicrobial: facts and gaps in knowledge. Crit. Rev. Microbiol., 2013, 39(4), 373-383.
[] [PMID: 22928774]

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