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Bioassay and bioactivity of polymer as carrier for some active compounds such as anticancer drugs

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Abstract

The present work deals with the development of a new slow release polymeric material, based on maize starch/cellulose acetate blend polymerized with acrylic acid monomer by free-radical mechanism. The polymerization was initiated by a redox system. The synthesized polymeric material may be used as a carrier for some active compounds such as anticancer drugs and has been characterized by Fourier transform spectroscopy. The active compounds are a new series of heterocyclic derivatives that had an anticancer effect and were prepared from pyrimidine and coumarin compounds, namely: 7-(2-methoxyphenyl)-5-thioxo-5,6-dihydro[1,2,4]triazolo[4,3-c] pyrimidine-8-carbonitrile (compound I), 8-(2-methoxyphenyl)-3,4-dioxo-6-thioxo-3,4,6,7-tetrahydro-2h-pyrimido[6,1-c]-[1,2,4]triazine-9-carbonitrile (compound II), and 4-substituted-1-(1-(7-methoxy-4-methyl-coumarin-8-yl) ethylidene) thiosemi-carbazide (compound III). They were incorporated into the prepared polymer matrix. The polymer-carried drug was tested for slow release drug delivery through testing it in aqueous media for different time periods and examining it as an anti-proliferative agent against human liver cancer cell line (HEPG2). The release rate of the drug was evaluated in aqueous media at different pHs as well as in dimethyl formamide which is the good solvent of such drugs. The release was measured spectrophotometrically. It was found that the release rate depends on the pH of the aqueous media. The release of the drug in the alkaline media was found to be high compared with other media. Also, the sustained release of the drug was extended to about 20 days. The activity of the released drug against human liver cancer cell line was tested. The results showed that compound (III) gave the highest growth inhibition activity followed by compound (II), while compound (I) indicated the lowest activity against the human liver (HEPG2) cancer cell line.

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References

  1. L. He-ping, Q. Long, W. Zhou-dong, L. Shan, Synthesis and characterization of ramose tetralactosyl-lysyl-chitosan-5-fluorouracil and its in vitro release. Res. Chem. Intermed. 38, 1421–1429 (2012)

    Article  Google Scholar 

  2. L. Hong-Wei, Z. Li-Ming, W. Chao, C. Ru-Fu, Preparation and properties of new micellar drug carriers based on hydrophobically modified amylopectin. Carbohydr. Polym. 83, 1499–1506 (2011)

    Article  Google Scholar 

  3. L.C.S. Pereira, A.M. Cunha, R.L. Reis, New starch-based thermoplastic hydrogels for use as bone cements or drug-delivery carriers. J. Mater. Sci. 9, 825–833 (1998)

    CAS  Google Scholar 

  4. P. Gawali, A. Gupta, S. Kachare, S. Kshirsagar, Formulation and evaluation of matrix-based sustained release tablets of quetiapine fumarate and the influence of excipients on drug release. J. Chem. Pharm.Res. 4, 3073–3081 (2012)

    CAS  Google Scholar 

  5. T. Kipping, H. Rein, Development of extruded starch based formulations aimed for local drug delivery to oral cavity. J. Pharm. Drug Deliv. Res. 1(1), 1000101 (2012)

    Article  Google Scholar 

  6. P. Callery, P. Gannett, in Cancer and cancer chemotherapy, eds by A. W. David, L. L. Thomas. Foye’s principles of medicinal chemistry fifth edition, vol. 38 (Lippincott Williams and Wilkins, Philadelphia, 2002), pp. 934–935

  7. R. Mishra, I. Tomar, Pyrimidine: the molecule of diverse biological and medicinal importance. IJPSR. 2(4), 758–771 (2011)

    CAS  Google Scholar 

  8. O.N. Al Safarjalani, R. Rais, J. Shi, R.F. Schinazi, F.N. Naguib, M.H. El Kouni, Modulation of 5-fluorouracil host-toxicity and chemotherapeutic efficacy against human colon tumors by 5-(Phenylthio)acyclouridine, a uridine phosphorylase inhibitor. Cancer Chemother. Pharmacol. 55, 541–551 (2005)

    Article  CAS  Google Scholar 

  9. M.S. Masoud, A.A. Ibrahim, E.A. Khalil, A. El-Marghany, Spectral properties of some metal complexes derived from uracil–thiouracil and citrazinic acid compounds. Spectrochim. Acta Part A Mol. Biomol. Spectrosc. 67, 662–668 (2007)

    Article  Google Scholar 

  10. J.B. Parker, J.T. Stivers, Dynamics of Uracil and 5-Fluorouracil in DNA. Biochemistry 50(5), 612–617 (2011)

    Article  CAS  Google Scholar 

  11. O.A. Fathalaa, W.A. Zaghary, H.H. Radwan, S.M. Awad, M.S. Mohamed, Synthesis of new 2-thiouracil-5-sulfonamide derivatives with biological activity Arch. Pharm. Res. 25(3), 258–269 (2002)

    Google Scholar 

  12. O.A. Fathalla, H.H. Radwan, S.M. Awad, M.S. Mohamed, Synthesis and biological evaluation of new pyrimidine derivatives. Indian J. Chem. 45B, 980–985 (2006)

    CAS  Google Scholar 

  13. A.A. Abu-Hashem, M.M. Youssef, H.A.R. Hussein, Synthesis, antioxidant, antituomer activities of some new thiazolopyrimidines, pyrrolothiazolopyrimidines and triazolopyrrolothiazolopyrimidines derivatives. J. Chin. Chem. Soc. 58, 41–48 (2011)

    Article  CAS  Google Scholar 

  14. S. Prachayasittikul, N. Sornsongkhram, R. Pingaew, S. Techatanachai, S. Ruchirawat, V. Prachayasittikul, Synthesis and novel bioactivities of substituted 6-propylthiouracils. European J. Sci. Res. 36(2), 236–245 (2009)

    Google Scholar 

  15. O.A. Fathalaa, H.S.M. Gad, A.S. Maghraby, Synthesis of new uracil-5-sulphonamide-p-phenyl derivatives and their effect on Biomphalaria alexandrina snail’s nucleoproteins Arch. Pharm. Res. 23, 128–138 (2000)

    Google Scholar 

  16. T.S. Chitre, K.G. Bothara, S.M. Patil, K.D. Asgaonkar, S. Nagappa, M.K. Kathiravan, Design, Synthesis, Docking and Anti-mycobacterial activity of some novel thiouracil derivatives as thymidine monophophate kinase (TMPKmt) inhibitors. Int. J. Res. Pharm. Biomed. Sci. 2, 616–623 (2011)

    Google Scholar 

  17. M. Roussaki, C.A. Kontogiorgis, D. Hadjipavlou-Litina, S. Hamilakis, A. Detsi, A novel synthesis of 3-aryl coumarins and evaluation of their antioxidant and lipoxygenase inhibitory activity. Bioorg. Med. Chem. Lett. 20, 3889–3892 (2010)

    Article  CAS  Google Scholar 

  18. I. Kostova, Synthetic and natural coumarins as cytotoxic agents. Curr. Med. Chem. Anticancer Agents 5, 29 (2005)

    Article  CAS  Google Scholar 

  19. Z.M. Nofal, M.I. El-Zahar, S.S. Abd El-Karim, Novel coumarin derivatives with expected biological activity. Molecules 5, 99–113 (2000)

    Article  CAS  Google Scholar 

  20. I. Kempen, D. Papapostolou, N. Thierry, L. Pochet, S. Counerotte, B. Masereel, J.-M. Foidart, M. Reboud-Ravaux, A. Noël, B. Pirotte, 3-Bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate inhibits cancer cell invasion in vitro and tumour growth in vivo. Br. J. Cancer 88, 1111–1118 (2003)

    Article  CAS  Google Scholar 

  21. S. Chen, M. Cho, K. Karlsberg, D. Zhou, Y.C. Yuan, Biochemical and biological characterization of a novel anti-aromatase coumarin derivative. J. Biol. Chem. 279(46), 48071–48078 (2004)

    Article  CAS  Google Scholar 

  22. O.A. Fathallaa, N.A. Mohameda, W.S. El-Serwya, H.F. AbdelHamidb, S.I. Abd El-Moezc, A.M. Soliman, Synthesis of some new pyrimidine derivatives and evaluation of their anticancer and antibacterial activities. Res. Chem. Intermed. (2012). doi:10.1007/s11164-012-0597-7

    Google Scholar 

  23. M.I. El-Zahar, S.S. Abd El-Karim, Synthesis and study of cytotoxic potency of novel coumarin derivatives agent breast cancer cell line. Egypt. J. Chem. 52, 431–450 (2009)

    Google Scholar 

  24. F.M. Helaly, A.I. Khalaf, D.E. El Nashar, Starch cellulose acetate co-acrylate (SCAA) polymer as a drug carrier. Res. Chem. Intermed. (2012). doi:10.1007/s11164-012-0833-1

    Google Scholar 

  25. F. Marson, J. Oil Color Chem. Assoc. 47, 323 (1964)

    Google Scholar 

  26. K.G. Das, Controlled Release Technology (Wiley Interscience, New York, 1983)

    Google Scholar 

  27. P. Skehan, R. Storeng, D. Scudiero, A. Anne Monks, J. McMahon, D. Vistica, J. Warren, H. Bokesch, S. Kenney, M. Boyd, New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl Cancer Inst. 82, 1107–1112 (1990)

    Article  CAS  Google Scholar 

  28. T. Higuchi, Rate of release of medicaments from ointment bases containing drugs in suspension. J. Pharm. Sci. 50, 874–875 (1961)

    Article  CAS  Google Scholar 

  29. T. Higuch, Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J. Pharm. Sci. 52, 1145–1149 (1963)

    Article  Google Scholar 

  30. M.A. Kalam, M. Humayun, N. Parvez, S. Yadav, A. Garg, S. Amin, Y. Sultana, A. Ali, Release kinetics of modified pharmaceutical dosage forms: a review. Cont. J. Pharm. Sci. 1, 30–35 (2007)

    Google Scholar 

  31. F.M. Helaly, D.E. El Nashar, A.I. Khalaf, Controlling the release of active iron and manganese ions from styrene-butadiene rubber-binding matrix containing chloride salts of them. J. Appl. Polym. Sci. 113, 811–817 (2009)

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Polymers and Pigment Department, National Research Center, Cairo, Egypt

    F. M. Helaly, A. I. Khalaf & D. E. El. Nashar

  2. Chemistry of Pesticides Department, National Research Center, Cairo, Egypt

    H. F. Abdel Hamid

  3. Therapeutic Chemistry Department, National Research Center, Cairo, Egypt

    A. M. Soliman

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  1. F. M. Helaly
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  2. A. I. Khalaf
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  3. D. E. El. Nashar
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  4. H. F. Abdel Hamid
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  5. A. M. Soliman
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Correspondence to D. E. El. Nashar.

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Helaly, F.M., Khalaf, A.I., Nashar, D.E.E. et al. Bioassay and bioactivity of polymer as carrier for some active compounds such as anticancer drugs. Res Chem Intermed 40, 749–760 (2014). https://doi.org/10.1007/s11164-012-0999-6

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