Sytnhesis of organoboron amide-ester branched derivatives of poly(Itaconic anhydride-alt-2-Vinyl-1,3-dioxolane) and cancer cells interaction studies

Year 2019, , 159 - 171, 31.12.2019

Gülten Özçayan

https://doi.org/10.30728/boron.515517

Cited By: 1

Abstract

New organaboron
amide-ester branched derivatives of poly(itaconic anhydride-alt-2-vinyl-1,3-dioxolane) are
synthesized by amidolysis and grafting reactions, respectively. The structure
and composition of the synthesized compounds are characterized by FTIR-ATR
(Fourier Transform-Infrared-Attenuated Total Reflection) and ¹H (¹³C)
NMR (Nuclear Magnetic Resonance) spectroscopy. These novel functionalized boron
containing biopolymers are interacted with HeLa (human cervix carcinoma
cell) cancer cells and L929 Fibroblast (normal) cells. Their anticancer properties are investigated
using a combination of different biochemical analysis methods. It is found that
both the values of the cytotoxicity and necrotic indexes are increased due to
organoboron linkage but these indexes of organoboron amide-ester derivative are
visibly decreased because of a-Hydroxy-ω- methoxypoly(ethylene oxide) (PEO)
biocompatibilization. The results of these studies allow us to utilize PEO
branched derivatives of synthesized organoboron copolymers (up to 200 µg mL^-1)
as therapeutic potential functional copolymer drugs in cancer chemotherapy and
boron-neutron capture therapy (BNCT).

Keywords

biopolymers, cytotoxicity, itaconic anhydride, organoboron copolymers, vinyl dioxolane

References

• [1] Milovanovic M. B., Trifunovic S. S., Katsikas I., Popovic I. G., Preparation and modification of itaconic anhydride-methyl methacrylate copolymers, J. Serb. Chem. Soc., 72 (12), 1507-1514, 2007.
• [2] Devrim Y. G., Rzaev Z. M. O., Pişkin E., Functionalization of isotactic polypropylene with citraconic anhydride, Polym. Bull., 59 (4), 447-456, 2007.
• [3] Drougas J., Guile R. L., Copolymerization of itaconic anhydride and styrene, determination of reactivity ratios, J. Polym. Sci., 55 (161), 297-302, 1961.
• [4] Ishida S., Saito S., Polymerization of itaconic acid derivatives, J. Polym. Sci. A1, 5, 689-705, 1967.
• [5] Shang S., Huang S. J., Weiss R. A., Synthesis and characterization of itaconic anhydride and stearyl methacrylate copolymers, Polymer, 50 (14), 3119-3127, 2009.
• [6] Papanu V. D., Amide-imide derivatives of homopolymers of itaconic anhydride having antitumor activity, USA patent, Monsanto Co., EP 0070142-A2, 1983.
• [7] Belov N., Reactive fluoropolymers synthesis and application, PhD thesis, Aachen University, Germany, 2011.
• [8] Müller F., Torger B., Allertz P. J., Jähnichena K., Keßler S. et al, Multifunctional crosslinkable itaconic acid copolymers for enzyme immobilization, Eur. Polym. J., 102, 47–55, 2018.
• [9] Li H., Zhang X., Zhang X., Yang B., Wei Y., Stable biocompatible cross-linked fluorescent polymeric nanoparticles based on AIE dye and itaconic anhydride, Colloid. Surfaces B., 121, 347–353, 2014.
• [10] Nayak P. S., Narayana B., Sarojini B. K, Sheik S., Shashidhara K.S., Chandrashekar K.R, Design, synthesis, molecular docking and biological evaluation of imides, pyridazines, and imidazoles derived from itaconic anhydride for potential antioxidant and antimicrobial activities, J. Taibah Univ. Sci., 10, 823–838, 2016.
• [11] Gupta V. K., Sood S., Agarwal S., Saini A. K., Pathania D., Antioxidant activity and controlled drug delivery potential of tragacanth gum-cl-poly (lactic acid-co-itaconic acid) hydrogel, Int. J. Biol. Macromol., 107, 2534–2543, 2018.
• [12] Rzaev Z. M. O., Complex-radical alternating copolymerization, Prog. Polym. Sci., 25, 163-217, 2000.
• [13] Kahraman G., Türk M., Rzayev Z. M. O., Söylemez E. A., Oğuztüzün S., Bioengineering functional copolymers. XX. Synthesis of novel anticancer active poly(maleic anhydride-alt-2-vinyl-1,3-dioxolane) and its organoboron amide-ester branched derivative, Hacettepe J. Biol. & Chem., 40 (2), 183-194, 2012.
• [14] Falco E. E., Patel M., Fisher J. P., Recent developments in cyclic acetal biomaterials for tissue engineering applications, Pharmaceut. Res., 25 (10), 2348-2356, 2008.
• [15] Patel M., Betz M. W., Geibel E., Patel K. J., Caccamese J. F., Coletti D. P., Sauk J. J., Fisher J. P., Cyclic acetal hydroxyapatite nanocomposites for orbital bone regeneration, Tissue Eng. Pt. A, 16 (1), 55-65, 2009.
• [16] Shi S., Gao H., Wu G., Nie J., Cyclic acetal as coinitiator for bimolecular photoinitiating systems, Polymer 48 (10), 2860–2865, 2007.
• [17] Rzayeva Z. M. O., Şimşek M., Bunyatovac U., Salamov B., Novel colloidal nanofiber semiconductor electrolytes from solution blends of PVA/ODA–MMT, poly (itaconic anhydride-alt-2-vinyl-1,3-dioxalan) and its Ag-carrying polymer complex by reactive electrospinning, Colloids and Surfaces A: Physicochem. Eng. Aspects, 492, 26–37, 2016.
• [18] Parab K., Boron containing vinyl aromatic polymers: synthesis, characterization and applications, PhD thesis, The State University of New Jersey, Newark, New Jersey, 2009.
• [19] Donmez Cavdar A., Mengeloglu F., Karakus K., Effect of boric acid and borax on mechanical, fire and thermal properties of wood flour filled high density polyethylene composites, Measurement, 60, 6–12, 2015.
• [20] Yang F., Mingyan Z., Zhang J., Zhou H., Synthesis of biologically active boron-containing compounds, Med. Chem. Commun., 9, 201-211, 2018.
• [21] Fernandes G.F.S., Denny W.A., Santos J.L.D, Boron in drug design: Recent advances in the development of new therapeutic agents, Eur. J. Med. Chem., 179, 791-804, 2019.
• [22] Takeuchi I., Nomura K., Makino K., Hydrophobic boron compound-loaded poly(L-lactide-co-glycolide) nanoparticles for boron neutron capture therapy, Colloid. Surfaces B., 159, 360–365, 2017.
• [23] Paşa, S., Synthesis and characterization of di-Schiff based boronic structures: Therapeutic investigation against cancer and implementation for antioxidant, J. Mol. Struct., 1195, 198-207, 2019. [24] Pasa S., Aydın S., Kalaycı S., Boğa M., Atlan M., Bingul M., Şahin F., Temel H., The synthesis of boronic-imine structured compounds and identification of their anticancer, antimicrobial and antioxidant activities, J. Pharmaceut. Anal., 6, 39–48, 2016.
• [25] Kaise A., Endo Y., Ohta K., Anti-cancer activity of m-carborane-containing trimethoxyphenyl derivatives through tubulin polymerization inhibition, Bioorg. Med. Chem., 27, 1139–1144, 2019.
• [26] Oleshkevich E., Morancho A, Saha A., Galenkamp K.M.O., Grayston A. et al., Combining magnetic nanoparticles and icosahedral boron clusters in biocompatible inorganic nanohybrids for cancer therapy, Nanomed-Nanotechnol., 20, 101986, 2019.
• [27] Cambre J. N., Roy D., Gondi S. R., Sumerlin B. S., Facile strategy to well-defined water-soluble boronic acid (co)polymers, J Am. Chem. Soc., 129, 10348–10349, 2007. [28] Camerano J. A., Casado M. A., Ciriano M. A., Oro L. A., Tris(pyrazolyl)borate carbosilane dendrimers and metallodendrimers, Dalton Trans., 44, 5287–5293, 2006.
• [29] Cheng F., Jakle F., RAFT polymerization of luminescent boron quinolate monomers, Chem. Commun., 46, 3717–3719, 2010.
• [30] Cheng F., Jakle F., Boron-containing polymers as versatile building blocks for functional nanostructured materials, Polym. Chem., 2 (10), 2122-2132, 2011.
• [31] Cui C., Bonder E. M., Jakle F., Weakly coordinating amphiphilic organoborate block copolymers, J. Am. Chem. Soc., 132, 1810-1812, 2010.
• [32] Cui C., Bonder E. M., Jakle F., Organoboronium amphiphilic block copolymers, J. Polym. Sci., Part A: Polym. Chem., 47 (23), 6612—6618, 2009.
• [33] Deore B. A., Freund M. S., Self-doped polyaniline nanoparticle dispersions based on boronic acid-phosphate complexation, Macromolecules, 42, 164-168, 2009.
• [34] Deore B. A., Yu I., Woodmass J., Freund M. S., Conducting Poly(anilineboronic acid) nanostructures: controlled synthesis and characterization, Macromol. Chem. Phys., 209 (11), 1094-1105, 2010.
• [35] Hoven C. V., Wang H., Elbing M., Garner L., Winkelhaus D., Bazan G. ,C., Chemically fixed p-n heterojunctions for polymer electronics by means of covalent B-F bond formation, Nat. Mater., 9 (3), 249-252, 2010.
• [36] Kahraman G., Beşkardeş O., Rzayev Z. M. O., Pişkin E., Bioengineering polyfunctional copolymers. VII. Synthesis and characterization of copolymers of p-vinylphenyl boronic acid with maleic and citraconic anhydrides and their self-assembled macrobranched supramolecular architectures, Polymer, 45 (17), 5813-5828, 2004.
• [37] Kahraman G., Türk M., Rzayev Z. M. O., Ünsal M. E., Söylemez E., Bioengineering functional copolymers. XV. Synthesis of organoboron amide-ester branched derivatives of oligo(maleic anhydride) and their interaction with HeLa and L929 fibroblast cells. Collection of Czechoslovak Chemical Communications, Collect Czech. Chem. C., 76 (8), 1013-1031, 2011.
• [38] Kataoka K., Miyazaki H., Okano T., Sakurai Y., Sensitive Glucose-Induced Change of the Lower Critical Solution Temperature of Poly[N,Ndimethylacrylamide-c0-3-(acry1amido)phenylboronic acid] in Physiological Saline, Macromolecules, 27, 1061-1062, 1994.
• [39] Kersey F. R., Zhang G. Q., Palmer G. M., Dewhirst M. W., Fraser C. L., Stereocomplexed PLA-PEG nanoparticles with dual-emissive boron dyes for tumor accumulation, ACS Nano, 4 (9), 4989-4996, 2010.
• [40] Kishi N., Ahn C. H., Jin J., Uozumi T., Sano T., Soga K., Synthesis of polymer supported borate cocatalysts and their application to metallocene polymerizations, Polymer, 41 (11), 4005-4012, 2000.
• [41] Mager M., Becke S., Windisch H., Denninger U., Noncoordinating dendrimer polyanions: cocatalysts for the metallocene-catalyzed olefin polymerization, Angew. Chem., Int. Ed., 40 (10), 1898-1902, 2001.
• [42] Pfister A., Zhang G., Zareno J., Horwitz A. F., Fraser C. L., Phosphorescence in aqueous medium, ACS Nano, 2, 1252-1258, 2008.
• [43] Qin Y., Sukul V., Pagakos D., Cui C., Jakle F., Preparation of organoboron block copolymers via ATRP of silicon and boron-functionalized monomers, Macromolecules, 38, 8987–8990, 2005.
• [44] Roy D., Cambre J. N., Sumerlin B. S., Sugar-responsive block copolymers by direct RAFT polymerization of unprotected boronic acid monomers, Chem. Commun., 21, 2477-2479, 2008.
• [45] Roy D., Cambre J. N., Sumerlin B. S., Triply-responsive boronic acidblock copolymers: solution self-assembly induced by changes in temperature, pH, or sugar concentration, Chem. Commun., 16, 2106-2108, 2009.
• [46] Rzayev Z. M. O., Türk M., Kahraman G., Pişkin E., Bioengineering functional copolymers. XIX. Synthesis of anhydride-organoboron functionalized copolymers and their interaction with cancer cells, Hacettepe J. Biol. & Chem., 39 (2), 111-132, 2011.
• [47] Türk M., Kahraman G., Khalilova S. A., Rzayev Z. M. O., Oguztüzün S., Bioengineering functional copolymers. XVII. Interaction of organoboron amide-ester branched derivatives of poly(acrylic acid) with cancer cells, J. Cancer Ther., 2 (2), 266–275, 2011.
• [48] Türk M., Rzayev Z. M. O., Kurucu G., Bioengineering functional copolymers. XII. Interaction of boron-containing and PEO branched derivatives of poly(MA-alt-MVE) with HeLa cells, Health, 2 (1) 51-61, 2010.
• [49] Zhang G., Chen J., Payne S. J., Kooi S. E., Demas J. N., Fraser C. L., Multi-Emissive difluoroboron dibenzoylmethane polylactide exhibiting intense fluorescence and oxygen-sensitive room-temperature phosphorescence, J. Am. Chem. Soc., 129 (29), 8942-8943, 2007.
• [50] Cicek H., Koçak G., Ceylan Ö., Bütün V., Synthesis and antibacterial activities of boronic acid-based recyclable spherical polymer brushes, Macromol. Res., 27 (7), 640-648, 2019.
• [51] Ahmadi Y., Siddiqui M.T., Mohd Q., Haq R., Ahmad S., Synthesis and characterization of surface-active antimicrobial hyperbranched polyurethane coatings based on oleo-ethers of boric acid, Arab. J. Chem., Avaliable online 10 July 2018.
• [52] He P., Zhu H., Ma Y., Liu N., Niu X., Wei M., Pan J., Rational design and fabrication of surface molecularly imprinted polymers based on multi-boronic acid sites for selective capture glycoproteins, Chem. Eng. J., 367, 55–63, 2019.
• [53] Hasabelnaby S., Goudah A., Agarwal H. K., Abd Alla M. S. M., Tjarks W., Synthesis, chemical and enzymatic hydrolysis, and aqueous solubility of amino acid ester prodrugs of 3-carboranyl thymidine analogs for boron neutron capture therapy of brain tumors, Eur. J. Med. Chem., 55, 325-334, 2012.
• [54] Sumitani S., Oishi M., Nagasaki Y., Carborane confined nanoparticles for boron neutron capture therapy: Improved stability, blood circulation time and tumor accumulation, React. Funct. Polym., 71 (7), 684-693, 2011.
• [55] Chen W., Mehta S. C., Lu D. R, Selective boron drug delivery to brain tumors for boron neutron capture therapy, Adv. Drug Deliver. Rev., 26 (2-3), 231-247, 1997.
• [56] Morin C., The chemistry of boron analogues of biomolecules, Tetrahedron, 50 (44), 12521-12569, 1994.
• [57] Valliant J. F., Guenther K. J., King A. S, Morel P., Schaffer P., Sogbein O. O., Stephenson K. A, The medicinal chemistry of carboranes, Coordin. Chem. Rev., 232 (1-2), 173-230, 2002.
• [58] Yang W., Gao S., Wang B., Boronic acid compounds as potential pharmaceutical agents, Med. Res. Rev., 23 (3), 346-368, 2003.