Vinca Hybrids with Antiproliferative Effect
Main Article Content
Abstract
Vinca alkaloids used in anticancer therapy are the well-known vinblastine and vincristine as classical antitumor agents. These dimeric molecules consist of two monomers, vindoline and catharanthine, which have no particular activity on their own. The goal in our research work was to obtain derivatives of one of these, vindoline, resulted in molecules with important antiproliferative effect. This type of derivatives were hybrids; vindoline was conjugated with several pharmacophores with and/or without linkers. Pharmacophores were amino acid esters, steroids, triazoles, and flavones. In several cases, the synthesized compounds showed on some cell lines an even better effect than vinblastine.
Keywords:
vinblastine, vindoline, hybrids, linkers, pharmacophores, antiproliferative activity
Article Details
How to Cite
MAYER, Szabolcs; KEGLEVICH, Péter; HAZAI, László.
Vinca Hybrids with Antiproliferative Effect.
Medical Research Archives, [S.l.], v. 10, n. 3, mar. 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2663>. Date accessed: 24 dec. 2024.
doi: https://doi.org/10.18103/mra.v10i3.2663.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Keglevich P, Hazai L, Kalaus G, Szántay C. Modifications on the Basic Skeletons of Vinblastine and Vincristine. Molecules. 2012; 17(5):5893-5914. https://doi.org/10.3390/molecules17055893.
2. Mayer S, Keglevich P, Keglevich A, Hazai L. New Anticancer Vinca Alkaloids in the Last Decade - A Mini-Review. Curr Org Chem. 2021; 25(10):1224-1234. https://doi.org/10.2174/1385272825666210216123256.
3. Nepali K, Sharma S, Sharma M, Bedi PMS, Dhar KL. Rational approaches, design strategies, structure activity relationship and mechanistic insights for anticancer hybrids. Eur J Med Chem. 2014; 77:422-487. https://doi.org/10.1016/j.ejmech.2014.03.018.
4. Choudhary S, Singh PK, Verma H, Singh H, Silkari O. Success stories of natural product-based hybrid molecules for multifactorial diseases. Eur J Med Chem. 2018; 151:62-97. https://doi.org/10.1016/j.ejmech.2018.03.057.
5. Passarella D, Giardini A, Peretto B, et al. Inhibitors of tubulin polymerization: Synthesis and biological evaluation of hybrids of vindoline, anhydrovinblastine and vinorelbine with thiocolchicine, podophyllotoxin and baccatin III. Bioorg Med Chem. 2008; 16(11):6269-6285. https://doi.org/10.1016/j.bmc.2008.04.025.
6. Ngo QA, Roussi F, Cormier A, et al. Synthesis and Biological Evaluation of Vinca Alkaloids and Phomopsin Hybrids. J Med Chem. 2009; 52(1):134-142. https://doi.org/10.1021/jm801064y.
7. Ngo QA, Roussi F, Thoret S, Guéritte F. Elaboration of Simplified Vinca Alkaloids and Phomopsin Hybrids. Chem Biol Drug Des. 2010; 75(3):284-294. https://doi.org/10.1111/j.1747-0285.2009.00922.x.
8. Gherbovet O, Coderch C, Alvarez MCG, et al. One-Pot Synthesis of Vinca Alkaloids-Phomopsin Hybrids. J Med Chem. 2014; 57(12):5470-5476. https://doi.org/10.1021/jm500530v.
9. Gherbovet O, Sanchez-Murcia PA, Alvarez MCG, et al. Synthesis and evaluation of hybrid molecules targeting the vinca domain of tubulin. Org Biomol Chem. 2015; 13(10):3144-3154. https://doi.org/10.1039/C4OB02114B.
10. Rannoux C, Roussi F, Martin M-T, Guéritte F. Elaboration of vinblastine hybrids using a reactive in situ generated N-carboxyanhydride. Org Biomol Chem. 2011; 9(13):4873-4881. https://doi.org/10.1039/C0OB01065K.
11. Ngo QA, Nguyen LA, Vo NB, et al. Synthesis and antiproliferativeactivity of new vinca alkaloids containing an ,-unsaturated aromatic side chain. Bioorg Med Chem Lett. 2015; 25(13):5597-5600. https://doi.org/10.1016/j.bmcl.2015.10.040.
12. Brady SF, Pawluczyk JM, Lumma PK, et al. Design and Synthesis of a Pro-Drug of Vinblastine Targeted at Treatment of Prostate Cancer with Enhanced Efficacy and Reduced Systemic Toxicity. J Med Chem. 2002; 45(21):4706-4715. https://doi.org/10.1021/jm020139f.
13. Bánóczi Z, Gorka-Kereskényi Á, Reményi J, et al. Synthesis and in Vitro Antitumor Effect of Vinblastine Derivative-Oligoarginine Conjugates. Bioconjug Chem. 2010; 21(11):1948-1955. https://doi.org/10.1021/bc100028z.
14. Bhushana Rao KSP, Collard MPM, Dejonghe JPC, Atassi G, Hannart JA, Trouet A. Vinblastin-23-oyl amino derivatives: chemistry, physicochemical data, toxicity, and antitumor activities against P388 and L1210 leukemias. J Med Chem. 1985; 28(8):1079-1088. https://doi.org/10.1021/jm00146a017.
15. Bánóczi Z, Keglevich A, Szabó I, et al. The effect of conjugation on antitumor activity of vindoline derivatives with octaarginine, a cell-penetrating peptide. J Pept Sci. 2018; 24(10):e3118. https://doi.org/10.1002/psc.3118.
16. Keglevich P, Hazai L, Gorka-Kereskényi Á, et al. Synthesis and in vitro Antitumor Effect of New Vindoline Derivatives Coupled with Amino Acid Esters. Heterocycles. 2013; 87(11):2299-2317. https://doi.org/10.3987/COM-13-12827.
17. Keglevich A, Dányi L, Rieder A, et al. Synthesis and Cytotoxic Activity of New Vindoline Derivatives Coupled to Natural and Synthetic Pharmacophores. Molecules. 2020; 25(4), 1010-1028. https://doi.org/10.3390/molecules25041010.
18. Keglevich A, Zsiros V, Keglevich P, et al. Synthesis and In Vitro Antitumor Effect of New Vindoline-steroid Hybrids. Curr Org Chem. 2019; 23(8):959-967. https://doi.org/10.2174/1385272823666190614113218.
19. Keglevich A, Szigetvári Á, Dékány M, Szántay C Jr, Keglevich P, Hazai L. Synthesis of vinca alkaloid–triphenylphosphine derivatives having potential antitumor effect. Phosphorus Sulfur Silicon Relat. Elem. 2019; 194(4-6):606-609. https://doi.org/10.1080/10426507.2018.1550780.
20. Keglevich A, Szigetvári Á, Dékány M, Szántay C Jr, Keglevich P, Hazai L. Synthesis and in vitro Antitumor Effect of New Vindoline Derivatives Coupled with Triphenylphosphine. Curr Org Chem. 2019; 23(7):852-858. https://doi.org/10.2174/1385272823666190524083236.
21. Mayer S, Keglevich A, Sepsey Für C, et al. Results in Chemistry of Natural Organic Compounds. Synthesis of New Anticancer Vinca Alkaloids and Flavone Alkaloids. Chemistry. 2020; 2(3):714-726. https://doi.org/10.3390/chemistry2030046.
22. Mayer S, Nagy N, Keglevich P, et al. Synthesis of Novel Vindoline-Chrysin Hybrids. Chem Biodivers. 2021; 19:e202100725. https://doi.org/10.1002/cbdv.202100725.
2. Mayer S, Keglevich P, Keglevich A, Hazai L. New Anticancer Vinca Alkaloids in the Last Decade - A Mini-Review. Curr Org Chem. 2021; 25(10):1224-1234. https://doi.org/10.2174/1385272825666210216123256.
3. Nepali K, Sharma S, Sharma M, Bedi PMS, Dhar KL. Rational approaches, design strategies, structure activity relationship and mechanistic insights for anticancer hybrids. Eur J Med Chem. 2014; 77:422-487. https://doi.org/10.1016/j.ejmech.2014.03.018.
4. Choudhary S, Singh PK, Verma H, Singh H, Silkari O. Success stories of natural product-based hybrid molecules for multifactorial diseases. Eur J Med Chem. 2018; 151:62-97. https://doi.org/10.1016/j.ejmech.2018.03.057.
5. Passarella D, Giardini A, Peretto B, et al. Inhibitors of tubulin polymerization: Synthesis and biological evaluation of hybrids of vindoline, anhydrovinblastine and vinorelbine with thiocolchicine, podophyllotoxin and baccatin III. Bioorg Med Chem. 2008; 16(11):6269-6285. https://doi.org/10.1016/j.bmc.2008.04.025.
6. Ngo QA, Roussi F, Cormier A, et al. Synthesis and Biological Evaluation of Vinca Alkaloids and Phomopsin Hybrids. J Med Chem. 2009; 52(1):134-142. https://doi.org/10.1021/jm801064y.
7. Ngo QA, Roussi F, Thoret S, Guéritte F. Elaboration of Simplified Vinca Alkaloids and Phomopsin Hybrids. Chem Biol Drug Des. 2010; 75(3):284-294. https://doi.org/10.1111/j.1747-0285.2009.00922.x.
8. Gherbovet O, Coderch C, Alvarez MCG, et al. One-Pot Synthesis of Vinca Alkaloids-Phomopsin Hybrids. J Med Chem. 2014; 57(12):5470-5476. https://doi.org/10.1021/jm500530v.
9. Gherbovet O, Sanchez-Murcia PA, Alvarez MCG, et al. Synthesis and evaluation of hybrid molecules targeting the vinca domain of tubulin. Org Biomol Chem. 2015; 13(10):3144-3154. https://doi.org/10.1039/C4OB02114B.
10. Rannoux C, Roussi F, Martin M-T, Guéritte F. Elaboration of vinblastine hybrids using a reactive in situ generated N-carboxyanhydride. Org Biomol Chem. 2011; 9(13):4873-4881. https://doi.org/10.1039/C0OB01065K.
11. Ngo QA, Nguyen LA, Vo NB, et al. Synthesis and antiproliferativeactivity of new vinca alkaloids containing an ,-unsaturated aromatic side chain. Bioorg Med Chem Lett. 2015; 25(13):5597-5600. https://doi.org/10.1016/j.bmcl.2015.10.040.
12. Brady SF, Pawluczyk JM, Lumma PK, et al. Design and Synthesis of a Pro-Drug of Vinblastine Targeted at Treatment of Prostate Cancer with Enhanced Efficacy and Reduced Systemic Toxicity. J Med Chem. 2002; 45(21):4706-4715. https://doi.org/10.1021/jm020139f.
13. Bánóczi Z, Gorka-Kereskényi Á, Reményi J, et al. Synthesis and in Vitro Antitumor Effect of Vinblastine Derivative-Oligoarginine Conjugates. Bioconjug Chem. 2010; 21(11):1948-1955. https://doi.org/10.1021/bc100028z.
14. Bhushana Rao KSP, Collard MPM, Dejonghe JPC, Atassi G, Hannart JA, Trouet A. Vinblastin-23-oyl amino derivatives: chemistry, physicochemical data, toxicity, and antitumor activities against P388 and L1210 leukemias. J Med Chem. 1985; 28(8):1079-1088. https://doi.org/10.1021/jm00146a017.
15. Bánóczi Z, Keglevich A, Szabó I, et al. The effect of conjugation on antitumor activity of vindoline derivatives with octaarginine, a cell-penetrating peptide. J Pept Sci. 2018; 24(10):e3118. https://doi.org/10.1002/psc.3118.
16. Keglevich P, Hazai L, Gorka-Kereskényi Á, et al. Synthesis and in vitro Antitumor Effect of New Vindoline Derivatives Coupled with Amino Acid Esters. Heterocycles. 2013; 87(11):2299-2317. https://doi.org/10.3987/COM-13-12827.
17. Keglevich A, Dányi L, Rieder A, et al. Synthesis and Cytotoxic Activity of New Vindoline Derivatives Coupled to Natural and Synthetic Pharmacophores. Molecules. 2020; 25(4), 1010-1028. https://doi.org/10.3390/molecules25041010.
18. Keglevich A, Zsiros V, Keglevich P, et al. Synthesis and In Vitro Antitumor Effect of New Vindoline-steroid Hybrids. Curr Org Chem. 2019; 23(8):959-967. https://doi.org/10.2174/1385272823666190614113218.
19. Keglevich A, Szigetvári Á, Dékány M, Szántay C Jr, Keglevich P, Hazai L. Synthesis of vinca alkaloid–triphenylphosphine derivatives having potential antitumor effect. Phosphorus Sulfur Silicon Relat. Elem. 2019; 194(4-6):606-609. https://doi.org/10.1080/10426507.2018.1550780.
20. Keglevich A, Szigetvári Á, Dékány M, Szántay C Jr, Keglevich P, Hazai L. Synthesis and in vitro Antitumor Effect of New Vindoline Derivatives Coupled with Triphenylphosphine. Curr Org Chem. 2019; 23(7):852-858. https://doi.org/10.2174/1385272823666190524083236.
21. Mayer S, Keglevich A, Sepsey Für C, et al. Results in Chemistry of Natural Organic Compounds. Synthesis of New Anticancer Vinca Alkaloids and Flavone Alkaloids. Chemistry. 2020; 2(3):714-726. https://doi.org/10.3390/chemistry2030046.
22. Mayer S, Nagy N, Keglevich P, et al. Synthesis of Novel Vindoline-Chrysin Hybrids. Chem Biodivers. 2021; 19:e202100725. https://doi.org/10.1002/cbdv.202100725.