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Paclitaxel as an anticancer agent: isolation, activity, synthesis and stability

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Paclitaxel is isolated from the Pacific yew. It can be obtained from the European yew, but only after chemical modification of the isolated compound by a semi-synthesis procedure. The procedure for total synthesis of paclitaxel is very complicated, involving multiple steps, and the yields of paclitaxel are meagre. This substance is also a metabolite of certain kinds of fungus. The microbiological pathway for producing paclitaxel compared with isolation from plant material involves shorter procuction times but a small yield. Cyclodextrins are usually used for improving the solubility of paclitaxel in aqueous media, with polymeric and other substances added. Paclitaxel has anticancer activity and use for preparing the formulations intravenously administrated to patients with tumors. The paclitaxel concentration in these formulations is determined using validated HPLC methods.
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  • Faculty of Technology, University of Nis, Bulevar oslobodjenja 124, 16000, Leskovac, Serbia,
  • Faculty of Technology, University of Nis, Bulevar oslobodjenja 124, 16000, Leskovac, Serbia
  • Faculty of Technology, University of Nis, Bulevar oslobodjenja 124, 16000, Leskovac, Serbia
  • Faculty of Technology, University of Nis, Bulevar oslobodjenja 124, 16000, Leskovac, Serbia
  • Faculty of Technology, University of Nis, Bulevar oslobodjenja 124, 16000, Leskovac, Serbia
  • Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000, Belgrade, Serbia
  • [1] Rowinsky E.K., Donehower R.C., Paclitaxel (taxol). N. Engl. J. Med., 1995, 332, 1004–1014[Crossref]
  • [2] Wani M.C., Taylor H.L., Wall M.E., Coggan P., McPhail A.T., Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia, J. Am. Chem. Soc., 1971, 93, 2325–2327[Crossref]
  • [3] Schiff PB, Fant J, Horwitz SB; Promotion of microtubule assembly in vitro by taxol. Nature 1979;(227):665–667
  • [4] Schiff P.B., Horwitz S.B., Taxol stabilizes microtubules in mouse fibroblast cells, PNAS 1980, 77, 1561–1565[Crossref]
  • [5] Rowinsky E.K., Cazenave L.A., Donehower R.C., Taxol: a novel investigational antimicrotubule agent, J. Natl. Cancer I 1990, 82, 1247–1259[Crossref]
  • [6] Stierle A., Strobel G., Stierle D., Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of pacific yew, Science 1993, 260, 214–216[Crossref]
  • [7] Guo B.H., Kai G.Y., Jin H.B., Tang K.X., Taxol synthesis. Afr. J. Biotechnol. 2006, 5(1), 15-20
  • [8] Strobel G., Yang X.S., Sears J., Kramer R., Sidhu R.S., Hess W.M., Taxol from Pestalotiopsis microspora, an endophytic fungus of Taxus wallachiana, Microbiology 1996, 142, 435–440[Crossref]
  • [9] Li J.Y., Stroble G., Sidhu R., Hess W.M., Ford E.J., Endophytic Taxolproducing fungi from bald cypress. Taxodium distichum, Microbiology 1996, 142, 2223–2226
  • [10] Wang J.F., Li G.L., Lu H.Y., Zheng Z.H., Huang Y.J., Su W.J., Taxol from Tubercularia sp. strain TF5, an endophytic fungus of Taxus mairei, FEMS Microbiol. Lett. 2000, 193, 249–253[Crossref]
  • [11] U. Breme, M. Caruso, N.C. Perellino, L. Fedeli, A. Pavesi, L. Piacenza, G. Ventrella, 2003. Paclitaxel production by Actinomycetes. U.S. patent 6,528,301
  • [12] Adler L.M., Herzog T.J., Williams S., Rader J.S., Mutch D.G., Analysis of exposure times and dose escalation of paclitaxel in ovarian cancer cell lines, Cancer 1994, 74, 1891–1898<1891::AID-CNCR2820740711>3.0.CO;2-K[Crossref]
  • [13] Richheimer S.L., Tinnermeier D.M., Timmons D.W., High-performance liquid chromatographic assay of taxol, Anal. Chem. 1992, 64(20), 2323–2326.[Crossref]
  • [14] Vyas D.M., Kadow J.F., Paclitaxel: A Unique Tubulin Interacting Anticancer Agent, Progr. Med. Chem. 1995, 32, 289–337[Crossref]
  • [15] Xu Q., Trissel L.A., Martinez J.F., Stability of paclitaxel in 5% dextrose injection or 0.9% sodium chloride injection at 4, 22, or 32 °C, Am. J. Hosp. Pharm. 1994, 51, 3058–3060
  • [16] T.B. Khac, M. Potier, 2004. Process for isolation and purification of paclitaxel from natural sources. U.S. patent 6,759,539
  • [17] S.S.K. Foo, Y. Bai, M. Ehlert, 2000. Method for high yield and large scale extraction of paclitaxel from paclitaxel-containing material. U.S. patent 6,136,989
  • [18] Kawamura F, Kikuchi Y, Ohira T, Yatagai M. Accelerated Solvent Extraction of Paclitaxel and Related Compounds from the Bark of Taxus cuspidate. J. Nat. Prod. 1999, 62(2), 244-247 [Crossref]
  • [19] Zu Y., Wang Y., Fu Y., Li S., Sun R., Liu W., Luo H., Enzyme-assisted extraction of paclitaxel and related taxanes from needles of Taxus chinensis, Sep. Purif. Technol. 2009, 68(2), 238–243[Crossref]
  • [20] P. Vemishetti, F.S. Gibson, J.L. Dillon, 2001. Semisynthesis of paclitaxel using dialkyildichlorosilanes. U.S. patent 6,242,614 B1
  • [21] Denis J.N., Greene A.E., Guenard D., Voegelein F.G., Potier L.M.P., Highly efficient, practical approach to natural taxol, J. Am. Chem. Soc. 1988, 110(17), 5917–5919[Crossref]
  • [22] R.A. Holton, 1993. Metal alkoxides. U.S. patent 5,274,124
  • [23] M.A. Poss, J.L. Moniot, I.D. Trifunovich, D.J. Kucera, J.K. Thottathil, S.H. Chen, J. Wei, 1994. Novel sidechain-bearing taxanes and intermediates thereof. W.O. patent 9414787
  • [24] Kingston D.G.I., Chaudhary A.G., Gunatilaka A.A.L., Middleton M.L., Tetrahedron. Lett. 1994, 35, 4483–4484[Crossref]
  • [25] Commerçon A., Bézard D., Bernard F., Bourzat J.D., Improved protection and esterification of a precursor of the taxotere® and taxol side chains, Tetrahedron. Lett. 1992, 33(36), 5185–5188[Crossref]
  • [26] Holton R.A., Somoza C., Kim H.B., Liang F., Biediger R.J., Boatman P.D., Shindo M., Smith C.C., Kim S., Nadizadeh H., Suzuki Y., Tao C., Yu P., Tang S., Zhang P., Murthi K.K., Gentile L.N., Liu J.H., First total synthesis of Taxol, J. Am. Chem. Soc. 1994, 116, 1597–1600[Crossref]
  • [27] Nicolaou K.C., Yang Z., Liu J.J., Ueno H., Nantermet P.G., Guy R.K., Claiborne C.F., Renaud J., Couladouros E.A., Paulvannan K., Sorensen E.J., Total synthesis of Taxol, Nature 1994, 367, 630–634[Crossref]
  • [28] Danishefsky S.J., Master J.J., Young W.B., Link J.T., Snyder L.B., Magee T.V., Jung D.K., Isaacs R.C.A., Bornmann W.G., Alaimo C.A., Coburn C.A., Di Grandi M.J., Total Synthesis of Baccatin III and Taxol, J. Am. Chem. Soc. 1996, 118, 2843–2859[Crossref]
  • [29] Morihira K., Hara R., Kawahara S., Nishimori T., Nakamura N., Kusama H., Kuwajima I., Enantio-selective total synthesis of Taxol, J. Am. Chem. Soc. 1998, 120, 12980–12981[Crossref]
  • [30] Nikolic V., Stankovic M., Kapor A., Nikolic Lj., Cvetkovic D., Stamenkovic J., Allylthiosulfinate: β-Cyclodextrin Inclusion Complex: Preparation, Characterization and Microbiological Activity, Die Pharmazie 2004, 59(11), 845–848
  • [31] Nikolic V., Nikolic Lj., Stankovic M., Kapor A., Popsavin M., Cvetkovic D., A molecular inclusion complex of atenolol with 2-hydroxypropyl-β-cyclodextrin; production and characterization thereof, J. Serb. Chem.Soc. 2007, 72(8–9), 737–746[Crossref]
  • [32] Nikolic V., Ilic D., Nikolic Lj., Stankovic M., Cakic M, Stanojevic Lj., Kapor A., Popsavin M., The protection of Nifedipin from photodegradation due to complex formation with β-cyclodextrin, Cent. Eur. J. Chem. 2010, 8(4), 744–749[Crossref]
  • [33] Savic I., Nikolic G., Savic I., Cakic M., Studies of the forced hydrolysis degradation of copper complexes with different oligosaccharides, Russ. J. Phys. Chem. A 2010, 84(13), 2306–2313[Crossref]
  • [34] Savic I., Nikolic G., Savic I., Cakic M., Conductometric studies on the stability of copper complexes with different oligosaccharides, Cent. Eur. J. Chem. 2010, 8(5), 1078–1085[Crossref]
  • [35] Sharma U.S., Balasubramanian S.V., Straubinger R.M., Pharmaceutical and physical properties of paclitaxel (Taxol) complexes with cyclodextrins, J. Pharm. Sci. 1995,84(10), 1223–1230[Crossref]
  • [36] Hamada H., Ishihara K., Masuoka N., Mikuni K., Nakajima N., Enhancement of Water-Solubility and Bioactivity of Paclitaxel using Modified Cyclodextrins, J. Biosci. Bioeng. 2006, 102(4), 369–371[Crossref]
  • [37] Dordunoo S.K., Burt H.M., Solubility and stability of paclitaxel: effects of buffers and cyclodextrins, Int. J. Pharm. 1996, 133, 191–201[Crossref]
  • [38] R. Yong, G. Jianfeng, Y. Shuqin, W. Ling, 2009. Pharmaceutical composition comprising cyclodextrin paclitaxel inclusion and preparation method thereof. Eu patent 075010
  • [39] Lee S.C., Huh K.M., Lee J., Cho Y.W., Galinsky R.E., Park K., Hydrotropic Polymeric Micelles for Enhanced Paclitaxel Solubility: In Vitro and In Vivo Characterization, Biomacromolecules 2007, 8(1), 202–208[Crossref]
  • [40] Ma G., Yang J., Zhang L., Song C., Effective antitumor activity of paclitaxel-loaded poly (ɛ-caprolactone)/pluronic F68 nanoparticles after intratumoral delivery into the murine breast cancer model, Anti-cancer drugs 2010, 21(3), 261–269[Crossref]
  • [41] Oh K.S., Song J.Y., Cho S.H., Lee B.S., Kim S.Y., Kim K., Jeon H., Kwon I.C., Yuk S.H., Paclitaxel-loaded Pluronic nanoparticles formed by a temperature-induced phase transition for cancer therapy, J. Control. Releas. 2010; doi:10.1016/j.jconrel.2010.08.021 [Crossref]
  • [42] C. Mahesh, W. Jane, R.E. Barrett, 2005. Method for preparing submicron particles of paclitaxel. W.O. patent 0466712005
  • [43] Tomas E., Karel U., Blanka R., Milada S., Design, Synthesis and Applications of Hyaluronic Acid-Paclitaxel Bioconjugates, Molecules 2008, 13, 360–378[Crossref]
  • [44] Leonelli F., Bella A.L., Migneco L.M., Bettolo R.M., Design, Synthesis and Applications of Hyaluronic Acid-Paclitaxel Bioconjugates, Molecules 2008, 13, 360–378[Crossref]
  • [45] B. Martin, C. Ladisav, S. Roman, S. Pavel, 2006. Process for the isolation of paclitaxel. W.O. patent 014356
  • [46] K.V. Rao, 1995. Method for the isolation and purification of taxol and its natural analogues. U.S. patent 5,475,120
  • [47] Rao K.V., Taxol and related taxanes. I. Taxanes of Taxus brevifolia bark, Pharm. Res. 1993, 10(4), 521–524[Crossref]
  • [48] Wall M.E., Wani M.C., Camptothecin and Taxol: Discovery to Clinic-Thirteenth Bruce F. Cain Memorial Award Lecture, Cancer Rese. 1995, 55, 753–760
  • [49] Carlier M.F., Pantaloni D., Taxol Effect on Tubulin Polymerization and Associated Guanosinev 5′-Triphosphate Hydrolysis, Biochemistry 1983, 22, 4814–4822[Crossref]
  • [50] Schiff P.B., Fant J., Horwitz S.B., Promotion of microtubule assembly in vitro by taxol, Nature 1979, 277(5698), 665–667[Crossref]
  • [51] Georg G.I., Boge T.C., Cheruvallath Z.S., Clowers S.J., Harriman G.C.B., Hepperle M., Park H., The medical chemistry of taxol. In: Suffness M (ed.), Taxol science and applications., Boca Raton: CRC Press, 1995, pp. 317–375
  • [52] Nicolaou K.C., Dai W.M., Guy R.K., Chemistry and biology of taxol, Angew. Chem. Int. Edit. 1994, 33, 15–44[Crossref]
  • [53] Han Y., Chaudhary A.G., Chordia M.D., Sackett D.L., Ramirez B.P., Kingston D.G.I., Bane S., Interaction of a Fluorescent Derivative of Paclitaxel (Taxol) with Microtubules and Tubulin-Colchicine, Biochemistry 1996, 35, 14173–14183[Crossref]
  • [54] Horwitz S.B., Mechanizam of action of Taxol, Trends Pharmacol. Sci. 1992, 13(4), 134–136[Crossref]
  • [55] Suffness M., Taxol: From Discovery to Therapeutic Use, Ann. Rep. Med. Chem. 1993, 28, 305–314[Crossref]
  • [56] Horwitz S.B., Cohen D., Rao S., Ringel I., Shen H.J., Yang C.P., Taxol: mechanisms of action and resistance, J. Nati. Cancer I 1993, 15, 55–61
  • [57] Kingston D.G.I., Taxane Anticancer Agents, Chapter 15. USA: American Chemical Society, 1995
  • [58] Rowinsky E.K., Cazenave L.A., Donehower R.C., Taxol: a novel investigational antimicrotubule agent, J. Nati. Cancer I 1990, 82(15), 1247–1259[Crossref]
  • [59] Kant J., The Chemistry and Pharmacology of Taxol and Its Derivatives, 5 ed. New York, Pharmochemistry Library, Elsevier, 1995
  • [60] Boge T.C., Himes R.H., Velde D.G.V., Georg G.I., The effect of the aromatic rings of taxol on biological activity and solution conformation: synthesis and evaluation of saturated taxol and taxotere analogues, J. Med. Chem. 1994, 37(20), 3337–3343[Crossref]
  • [61] Rowinsky E.K., Donehower R.C., The clinical pharmacology and use of antimicrotubule agents in cancer chemotherapeutics, Pharmacol. Therapeut. 1991, 52(1), 35–84[Crossref]
  • [62] Schiff P.B., Horwitz S.B., Taxol stabilizes microtubules in mouse fibroblast cells, PNAS 1980, 77(3), 1561–1565[Crossref]
  • [63] Ding A.H., Porteu F., Sanchez E., Nathan C.F., Shared actions of endotoxin and taxol on TNF receptors and TNF release, Science 1990, 248(4953), 370–372[Crossref]
  • [64] Manthey C.L., Brandes M.E., Perera P.Y., Vogel S.N., Taxol increases steady-state levels of lipopolysaccharide-inducible genes and protein-tyrosine phosphorylation in murine macrophages, J. Immunol. 1992, 149(7), 2459–2465
  • [65] Ozcelik B., Turkyilmaz C., Ozgun M.T., Serin I.S., Batukan C., Ozdamar S., Ozturk A. Prevention of paclitaxel and cisplatin induced ovarian damage in rats by a gonadotropin-releasing hormone agonist. Fertil. Steril. 93(5), 1609–1614
  • [66] Sznitowska M., Klunder M., Placzek M., Paclitaxel Solubility in Aqueous Dispersions and Mixed Micellar Solutions of Lecithin, Chem. Pharm. Bull. 2008, 56(1), 70–74[Crossref]
  • [67] Kim S.C., Jaewon Y., Lee J.W., Seok P.E., Cheol C.S., Sensitive HPLC method for quantitation of paclitaxel (Genexol®) in biological samples with application to preclinical pharmacokinetics and biodistribution, J. Pharmaceut. Biomed. 2005, 39(1–2), 170–176[Crossref]
  • [68] Haruo Y., Mihoko N., Mitsuhiro W., Ken’ichiro N., Simultaneous HPLC determination of paclitaxel and verapamil in rat plasma, Chromatography 2005, 26(2), 49–50
  • [69] Baldrey S.F., Brodie R.R., Morris G.R., Jenkins E.H., Brookes S.T., Comparison of LC-UV and LCMS-MS for the Determination of Taxol, Chromatographia, 2005, 55, S-187–S-192
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