ARTICLE

APPROACHES OF PRODRUG DESIGNING TO TREAT CANCER NEURODEGENERATIVE DISORDERS AND VIRAL DISEASES

  1. HOME
  2. ARTICLE

04 Pages : 33-47

http://dx.doi.org/10.31703/gdddr.2020(V-I).04      10.31703/gdddr.2020(V-I).04      Published : Dec 2020

Approaches of Prodrug Designing to Treat Cancer, Neurodegenerative Disorders and Viral Diseases

Abstract

    Classical prodrug design is a sweeping approach to throw away futile side effects related to drug therapy. The main purpose of prodrug designing is to ameliorate physicochemical, pharmaceutical, and pharmacokinetic characteristics of particular compounds to resolve issues like formulation, delivery to the target site, and toxicity limitations. To fabricate the pharmacological action in CNS, drugs must cross the blood-brain barrier (BBB). Therefore, prodrug strategies are designed which include lipidization and the use of carriers and transporters. In this article, we have reviewed different anticancer, neuroprotective, and antiviral prodrugs. Flurbiprofen prodrugs, glycosylated prodrugs, resveratrol prodrugs, levodopa, etc., are mapped out for neurodegenerative disorders in CNS. Due to the poor oral pharmacokinetic properties of antiviral agents, drug design methods are performed by combining the parent drug molecule with a number of active components such as dipeptide esters, amino acids, nucleosides, and macromolecular-based prodrugs.

    Cytochrome P450, Doxorubicin, Drug Delivery, Blood-Brain Barrier, Prodrug Design, Levodopa

    (1) Muhammad Shehzeb Ashraf
    Undergraduate Final year students, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
    (2) Iqra Rehman
    Undergraduate Final year students, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
    (3) Urooj Fatima
    Undergraduate Final year students, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
    (4) Mubashar Rehman
    Assistant Professor, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Fulltext PDF

References

  • Abdul-Hay, S. O., Luo, J., Ashghodom, R. T., & Thatcher, G. R. J. (2009). NO-flurbiprofen reduces amyloid-β, is neuroprotective in cell culture, and enhances cognition in response to cholinergic blockade. Journal of Neurochemistry, 111(3), 766-776. https://doi.org/10.1111/j.1471- 4159.2009.06353.x
  • Choudhary, D., Goykar, H., Kalyane, D., Sreeharsha, N., & Tekade, R. K. (2020). Prodrug design for improving the biopharmaceutical properties of therapeutic drugs. In The Future of Pharmaceutical Product Development and Research. INC. https://doi.org/10.1016/b978-0- 12-814455-8.00006-2
  • Al-Azzawi, S., Masheta, D., Guildford, A., Phillips, G., & Santin, M. (2020). A peptide-based nanocarrier for an enhanced delivery and targeting of flurbiprofen into the brain for the treatment of alzheimer's disease: An in vitro study. Nanomaterials, 10(8), 1-18. https://doi.org/10.3390/nano10081590
  • Christophe, R., & Patrick, D. (2018). PLEIOTROPIC PRODRUGS : A NOVEL POLYPHARMACO- LOGY APPROACH TO TREAT NEURODEGENERATIVE. 87(supplementum 1), 3187.
  • Auciello, G., Marco, A. Di, Paz, O. G., Malancona, S., Harper, S., Beconi, M., ... Elbaum, D. (2020). Cyclic Phosphopantothenic Acid Prodrugs for Treatment of Pantothenate Kinase-Associated Neurodegeneration. https://doi.org/10.1021/acs.jmedchem.0c0153 1
  • Dankyi, B. O., Amponsah, S. K., Allotey-Babington, G. L., Adams, I., Goode, N. A., & Nettey, H. (2020). Chitosan-Coated Hydroxypropylmethyl Cellulose Microparticles of Levodopa (and Carbidopa): In Vitro and Rat Model Kinetic Characteristics. Current Therapeutic Research - Clinical and Experimental, 93, 100612. https://doi.org/10.1016/j.curtheres.2020.1006 12
  • Back, D., & Marzolini, C. (2020). The challenge of HIV treatment in an era of polypharmacy. Journal of the International AIDS Society, 23(2), 1-12. https://doi.org/10.1002/jia2.25449
  • Denny, W. A. (2004). Tumor-activated prodrugs - A new approach to cancer therapy. Cancer Investigation, 22(4), 604-619. https://doi.org/10.1081/CNV-200027148
  • Banks, W. A. (2009). Characteristics of compounds that cross the blood-brain barrier. BMC Neurology, 9(SUPPL. 1), 5-9. https://doi.org/10.1186/1471-2377-9-S1-S3
  • Denny, W. A., & Wilson, W. R. (1998). Therapies *. 387-394.
  • Beauchamp, L. M., Orr, G. F., De Miranda, P., Burnette, T., & Krenitsky, T. A. (1992). Amino acid ester prodrugs of acyclovir. Antiviral Chemistry and Chemotherapy, 3(3), 157-164. https://doi.org/10.1177/095632029200300305
  • Dong, Z., Li, Q., Guo, D., Shu, Y., & Polli, J. E. (2015). Synthesis and Evaluation of Bile Acid-Ribavirin Conjugates as Prodrugs to Target the Liver. Journal of Pharmaceutical Sciences, 104(9), 2864-2876. https://doi.org/10.1002/jps.24375
  • Bondì, M. L., Craparo, E. F., Picone, P., Giammona, G., Di Gesù, R., & Di Carlo, M. (2013). Lipid nanocarriers containing ester prodrugs of flurbiprofen preparation, physical-chemical characterization and biological studies. Journal of Biomedical Nanotechnology, 9(2), 238-246. https://doi.org/10.1166/jbn.2013.1490
  • Erion, M. D., Reddy, K. R., Boyer, S. H., Matelich, M. C., Gomez-Galeno, J., Lemus, R. H., ... Van Poelje, P. D. (2004). Design, Synthesis, and Characterization of a Series of Cytochrome P 450 3A-Activated Prodrugs (HepDirect Prodrugs) Useful for Targeting Phosph(on)ate- Based Drugs to the Liver. Journal of the American Chemical Society, 126(16), 5154- 5163. https://doi.org/10.1021/ja031818y
  • Chang, H. T., Pan, H. J., & Lee, C. H. (2018). Prevention of Tamoxifen-related Nonalcoholic Fatty Liver Disease in Breast Cancer Patients. Clinical Breast Cancer, 18(4), e677-e685. https://doi.org/10.1016/j.clbc.2017.11.010
  • Ettmayer, P., Amidon, G. L., Clement, B., & Testa, B. (2004). Lessons Learned from Marketed and Investigational Prodrugs. Journal of Medicinal Chemistry, 47(10), 2393-2404. https://doi.org/10.1021/jm0303812
  • Chien, M., Anderson, T. K., Jockusch, S., Tao, C., Li, X., Kumar, S., ... Ju, J. (2020). Nucleotide Analogues as Inhibitors of SARS-CoV-2 Polymerase, a Key Drug Target for COVID-19. Journal of Proteome Research, 19(11), 4690-4697. https://doi.org/10.1021/acs.jproteome.0c0039 2
  • Ferrara, S. J., & Scanlan, T. S. (2020). A CNS-Targeting Prodrug Strategy for Nuclear Receptor Modulators. Journal of Medicinal Chemistry, 63(17), 9742-9751. https://doi.org/10.1021/acs.jmedchem.0c0086 8
  • Gray, R., Ives, N., Rick, C., Patel, S., Gray, A., Jenkinson, C., ... Whittuck, M. (2014). Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors compared with levodopa as initial treatment for Parkinson's disease (PD MED): A large, open-label, pragmatic randomised trial. The Lancet, 384(9949), 1196-1205. https://doi.org/10.1016/S0140-6736(14)60683- 8
  • Huttunen, K. M., Mähönen, N., Raunio, H., & Rautio, J. (2008). Cytochrome P450-Activated Prodrugs : Targeted Drug Delivery. 2346-2365.
  • Gray, R., Ives, N., Rick, C., Patel, S., Gray, A., Jenkinson, C., ... Whittuck, M. (2014). Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors compared with levodopa as initial treatment for Parkinson's disease (PD MED): A large, open-label, pragmatic randomised trial. The Lancet, 384(9949), 1196-1205. https://doi.org/10.1016/S0140-6736(14)60683- 8
  • Investigation, P., & Hepatotoxicity, A. C. I. (2011). Asian Journal of Pharmaceutical and Health Sciences. 1-5.
  • Gynther, M., Laine, K., Ropponen, J., Leppänen, J., Mannila, A., Nevalainen, T., ... Rautio, J. (2008). Large neutral amino acid transporter enables brain drug delivery via prodrugs. Journal of Medicinal Chemistry, 51(4), 932-936. https://doi.org/10.1021/jm701175d
  • Jana, S., Mandlekar, S., & Marathe, P. (2010). Prodrug Design to Improve Pharmacokinetic and Drug Delivery Properties: Challenges to the Discovery Scientists. Current Medicinal Chemistry, 17(32), 3874-3908. https://doi.org/10.2174/092986710793205426
  • Han, H. K., & Amidon, G. L. (2000). Targeted prodrug design to optimize drug delivery. AAPS PharmSci, 2(1), 1-11. https://doi.org/10.1208/ps020106
  • Järvinen, T., Rautio, J., Masson, M., & Loftsson, T. (2005). Design and Pharmaceutical Applications of Prodrugs. Drug Discovery Handbook, 733- 796. https://doi.org/10.1002/0471728780.ch17
  • Henderson, J. T., & Piquette-Miller, M. (2015). Blood- brain barrier: an impediment to neuropharmaceuticals. Clinical Pharmacology and Therapeutics, 97(4), 308-313. https://doi.org/10.1002/cpt.77
  • Jiang, Q., Zhong, Q., Zhang, Q., Zheng, S., & Wang, G. (2012). Boron-based 4-hydroxytamoxifen bioisosteres for treatment of de novo tamoxifen resistant breast cancer. ACS Medicinal Chemistry Letters, 3(5), 392-396. https://doi.org/10.1021/ml3000287
  • Hinton, T. M., Zuwala, K., Deffrasnes, C., Todd, S., Shi, S., Marsh, G. A., ... Zelikin, A. N. (2016). Polyanionic Macromolecular Prodrugs of Ribavirin: Antiviral Agents with a Broad Spectrum of Activity. Advanced Healthcare Materials, 5(5), 534-540. https://doi.org/10.1002/adhm.201500841
  • Juncos, J. L., Fabbrini, G., Mouradian, M. M., & Chase, T. N. (1987). Controlled Release Levodopa- Carbidopa (CR-5) in the Management of Parkinsonian Motor Fluctuations. Archives of Neurology, 44(10), 1010-1012. https://doi.org/10.1001/archneur.1987.005202 20016008
  • Ho, N. F. H., & Higuchix, W. I. (1979). PHARMACEUTICAL SCIENCES @ Physical Model Evaluation of. 68(11), 1341-1346.
  • Kim, M., Park, M. H., Nam, G., Lee, M., Kang, J., Song, I.-S., ... Lim, M. H. (2020). A Glycosylated Prodrug to Attenuate Neuroinflammation and Improve Cognitive Deficits in Alzheimer's Disease Transgenic Mice. Molecular Pharmaceutics. https://doi.org/10.1021/acs.molpharmaceut.0c 00677
  • Hong, J., Huang, J., Shen, L., Zhu, S., Gao, W., Wu, J., ... Shen, K. (2020). A prospective, randomized study of Toremifene vs. tamoxifen for the treatment of premenopausal breast cancer: Safety and genital symptom analysis. BMC Cancer, 20(1), 1-10. https://doi.org/10.1186/s12885-020-07156-x
  • Kishimoto, Y., Johnson, J., Fang, W., Halpern, J., Marosi, K., Liu, D., ... Mattson, M. P. (2020). A mitochondrial uncoupler prodrug protects dopaminergic neurons and improves functional outcome in a mouse model of Parkinson's disease. Neurobiology of Aging, 85, 123-130. https://doi.org/10.1016/j.neurobiolaging.2019. 09.011
  • Hou, J., & Liu, Y. (2020). Magnetically Directed Enzyme / Prodrug Prostate Cancer Therapy Based on β -Glucosidase / Amygdalin.
  • Kratz, F., Mansour, A., Soltau, J., Warnecke, A., Fichtner, I., Unger, C., & Drevs, J. (2005). Development of albumin-binding doxorubicin pro-drugs that are cleaved by prostate-specific antigen. Archiv Der Pharmazie, 338(10), 462- 472. https://doi.org/10.1002/ardp.200500130
  • Huang, P. S., & Oliff, A. (2001). Drug-targeting strategies in cancer therapy. Current Opinion in Genetics and Development, 11(1), 104-110. https://doi.org/10.1016/S0959-437X(00)00164- 7
  • Kryger, M. B. L., Wohl, B. M., Smith, A. A. A., & Zelikin, A. N. (2013). Macromolecular prodrugs of ribavirin combat side effects and toxicity with no loss of activity of the drug. Chemical Communications, 49(26), 2643-2645. https://doi.org/10.1039/c3cc00315a
  • Lee, H. J., Cooperwood, J. S., You, Z., Ko, D. H., & Pyoung, H. H. (2002). Prodrug and antedrug: Two diametrical approaches in designing safer drugs. Archives of Pharmacal Research, 25(2), 111-136. https://doi.org/10.1007/BF02976552
  • Najjar, A., & Karaman, R. (2019). The prodrug approach in the era of drug design. Expert Opinion on Drug Delivery, 16(1), 1-5. https://doi.org/10.1080/17425247.2019.15539 54
  • Li, J. Y., Boado, R. J., & Pardridge, W. M. (2001). Blood - Brain Barrier Genomics. 61-68
  • Neeraj, A., Chandrasekar, M. J. N., Sara, U. V. S., & Rohini, A. (2011). Poly(HEMA-Zidovudine) conjugate: A macromolecular pro-drug for improvement in the biopharmaceutical properties of the drug. Drug Delivery, 18(4), 272-280. https://doi.org/10.3109/10717544.2010.53627 2
  • Mailman, R. B., Yang, Y., & Huang, X. (2021). D1 , not D2 , dopamine receptor activation dramatically improves MPTP-induced parkinsonism unresponsive to levodopa. European Journal of Pharmacology, 892(November 2020), 173760. https://doi.org/10.1016/j.ejphar.2020.173760
  • Oliveri, V. (2015). New Glycoconjugates for the Treatment of Diseases Related to Metal Dyshomeostasis. ChemistryOpen, 4(6), 792- 795. https://doi.org/10.1002/open.201500155
  • Mandal, A., Cholkar, K., Khurana, V., Shah, A., Agrahari, V., Bisht, R., ... Mitra, A. K. (2017). Topical Formulation of Self-Assembled Antiviral Prodrug Nanomicelles for Targeted Retinal Delivery. Molecular Pharmaceutics, 14(6), 2056-2069. https://doi.org/10.1021/acs.molpharmaceut.7b 00128
  • Pardridge, W. M. (2002). Why is the global CNS pharmaceutical market so under-penetrated? Drug Discovery Today, 7(1), 5-7. https://doi.org/10.1016/S1359-6446(01)02082- 7
  • Manish, M., Lynn, A. M., & Mishra, S. (2020). Cytochrome P450 2C9 polymorphism: Effect of amino acid substitutions on protein flexibility in the presence of tamoxifen. Computational Biology and Chemistry, 84, 107166. https://doi.org/10.1016/j.compbiolchem.2019. 107166
  • Peñalver, P., Belmonte-Reche, E., Adán, N., Caro, M., Mateos-Martín, M. L., Delgado, M., ... Morales, J. C. (2018). Alkylated resveratrol prodrugs and metabolites as potential therapeutics for neurodegenerative diseases. European Journal of Medicinal Chemistry, 146, 123-138. https://doi.org/10.1016/j.ejmech.2018.01.037
  • Meanwell, N. A., Krystal, M. R., Nowicka-Sans, B., Langley, D. R., Conlon, D. A., Eastgate, M. D., ... Kadow, J. F. (2018). Inhibitors of HIV-1 Attachment: The Discovery and Development of Temsavir and its Prodrug Fostemsavir. Journal of Medicinal Chemistry, 61(1), 62-80. https://doi.org/10.1021/acs.jmedchem.7b0133 7
  • Perioli, L., Ambrogi, V., Bernardini, C., Grandolini, G., Ricci, M., Giovagnoli, S., & Rossi, C. (2004). Potential prodrugs of non-steroidal anti- inflammatory agents for targeted drug delivery to the CNS. European Journal of Medicinal Chemistry, 39(8), 715-727. https://doi.org/10.1016/j.ejmech.2004.05.006
  • Meinig, J. M., Ferrara, S. J., Banerji, T., Banerji, T., Sanford-Crane, H. S., Bourdette, D., & Scanlan, T. S. (2019). Structure-Activity Relationships of Central Nervous System Penetration by Fatty Acid Amide Hydrolase (FAAH)-Targeted Thyromimetic Prodrugs. ACS Medicinal Chemistry Letters, 10(1), 111-116. https://doi.org/10.1021/acsmedchemlett.8b00 501
  • Peura, L., Malmioja, K., Laine, K., Leppänen, J., Gynther, M., Isotalo, A., & Rautio, J. (2011). Large amino acid transporter 1 (LAT1) prodrugs of valproic acid: New prodrug design ideas for central nervous system delivery. Molecular Pharmaceutics, 8(5), 1857-1866. https://doi.org/10.1021/mp2001878
  • Montaser, A. B., Järvinen, J., Löffler, S., Huttunen, J., Auriola, S., Lehtonen, M., ... Huttunen, K. M. (2020). L-Type Amino Acid Transporter 1 Enables the Efficient Brain Delivery of Small- Sized Prodrug across the Blood-Brain Barrier and into Human and Mouse Brain Parenchymal Cells. ACS Chemical Neuroscience. https://doi.org/10.1021/acschemneuro.0c0056 4
  • Psimadas, D., Georgoulias, P., Valotassiou, V., & Loudos, G. (2012). Molecular Nanomedicine Towards Cancer : Journal of Pharmaceutical Sciences, 101(7), 2271-2280. https://doi.org/10.1002/jps
  • Rasheed, A., & Kumar, C. K. A. (2008). Novel approaches on prodrug based drug design. Pharmaceutical Chemistry Journal, 42(12), 677- 686. https://doi.org/10.1007/s11094-009- 0213-3
  • Smith, A. A. A., Kryger, M. B. L., Wohl, B. M., Ruiz- Sanchis, P., Zuwala, K., Tolstrup, M., & Zelikin, A. N. (2014). Macromolecular (pro)drugs in antiviral research. Polymer Chemistry, 5(22), 6407-6425.
  • Rautio, J., Meanwell, N. A., Di, L., & Hageman, M. J. (2018). The expanding role of prodrugs in contemporary drug design and development. Nature Reviews Drug Discovery, 17(8), 559-587. https://doi.org/10.1038/nrd.2018.46
  • Smith, A. A. A., Wohl, B. M., Kryger, M. B. L., Hedemann, N., Guerrero-Sanchez, C., Postma, A., & Zelikin, A. N. (2014). Macromolecular prodrugs of Ribavirin: Concerted efforts of the carrier and the drug. Advanced Healthcare Materials, 3(9), 1404-1407. https://doi.org/10.1002/adhm.201300637
  • Ruiz-Sanchis, P., Wohl, B. M., Smith, A. A. A., Zuwala, K., Melchjorsen, J., Tolstrup, M., & Zelikin, A. N. (2015). Highly active macromolecular prodrugs inhibit expression of the hepatitis c virus genome in the host cells. Advanced Healthcare Materials, 4(1), 65-68. https://doi.org/10.1002/adhm.201400307
  • Smith, A. A. A., Zuwala, K., Kryger, M. B. L., Wohl, B. M., Guerrero-Sanchez, C., Tolstrup, M., ... Zelikin, A. N. (2015). Macromolecular prodrugs of ribavirin: Towards a treatment for co- infection with HIV and HCV. Chemical Science, 6(1), 264-269. https://doi.org/10.1039/c4sc02754j
  • Ryan, A. T., Pulukuri, A. J., Davaritouchaee, M., Abbasi, A., Hendricksen, A. T., Opp, L. K., ... Mancini, R. J. (2020). Comparing the immunogenicity of glycosidase-directed resiquimod prodrugs mediated by cancer cell metabolism. Acta Pharmacologica Sinica, 41(7), 995-1004. https://doi.org/10.1038/s41401- 020-0432-4
  • Sofia, M. J. (2013). Nucleotide prodrugs for the treatment of HCV infection. In Advances in Pharmacology (1st ed., Vol. 67). Copyright © 2013 Elsevier Inc. All rights reserved. https://doi.org/10.1016/B978-0-12-405880- 4.00002-0
  • Santos, C. R., Capela, R., Pereira, C. S. G. P., Valente, E., Gouveia, L., Pannecouque, C., ... Gomes, P. (2009). Structure-activity relationships for dipeptide prodrugs of acyclovir: Implications for prodrug design. European Journal of Medicinal Chemistry, 44(6), 2339-2346. https://doi.org/10.1016/j.ejmech.2008.08.009
  • Song, H., Quan, F., Yu, Z., Zheng, M., Ma, Y., Xiao, H., & Ding, F. (2019). Carboplatin prodrug conjugated Fe 3 O 4 nanoparticles for magnetically targeted drug delivery in ovarian cancer cells. Journal of Materials Chemistry B, 7(3), 433-442. https://doi.org/10.1039/c8tb02574f
  • Scott, L. E., Telpoukhovskaia, M., Rodríguez- Rodríguez, C., Merkel, M., Bowen, M. L., Page, B. D. G., ... Orvig, C. (2011). N-Aryl-substituted 3-(b- D-glucopyranosyloxy)-2-methyl-4(1H)- pyridinones as agents for Alzheimer's therapy. Chemical Science, 2(4), 642-648. https://doi.org/10.1039/c0sc00544d
  • Talluri, R. S., Samanta, S. K., Gaudana, R., & Mitra, A. K. (2008). Synthesis, metabolism and cellular permeability of enzymatically stable dipeptide prodrugs of acyclovir. International Journal of Pharmaceutics, 361(1-2), 118-124. https://doi.org/10.1016/j.ijpharm.2008.05.024
  • Shen, W., Kim, J. S., Kish, P. E., Zhang, J., Mitchell, S., Gentry, B. G., ... Hilfinger, J. (2009). Design and synthesis of vidarabine prodrugs as antiviral agents. Bioorganic and Medicinal Chemistry Letters, 19(3), 792-796. https://doi.org/10.1016/j.bmcl.2008.12.031
  • Tampio, J., Huttunen, J., Montaser, A., & Huttunen, K. M. (2020). Targeting of Perforin Inhibitor into the Brain Parenchyma Via a Prodrug Approach Can Decrease Oxidative Stress and Neuroinflammation and Improve Cell Survival. Molecular Neurobiology, 57(11), 4563-4577. https://doi.org/10.1007/s12035-020-02045-7
  • Sinokrot, H., Smerat, T., Najjar, A., & Karaman, R. (2017). Advanced prodrug strategies in nucleoside and non-nucleoside antiviral agents: A review of the recent five years. Molecules, 22(10). https://doi.org/10.3390/molecules22101736
  • Tolle-Sander, S., Lentz, K. A., Maeda, D. Y., Coop, A., & Polli, J. E. (2004). Increased acyclovir oral bioavailability via a bile acid conjugate. Molecular Pharmaceutics, 1(1), 40-48. https://doi.org/10.1021/mp034010
  • Toublet, F.-X., Lalut, J., Hatat, B., Lecoutey, C., Davis, A., Since, M., ... Rochais, C. (2020). Pleiotropic prodrugs: Design of a dual butyrylcholinesterase inhibitor and 5-HT6 receptor antagonist with therapeutic interest in Alzheimer's disease. European Journal of Medicinal Chemistry, In Press,. https://doi.org/10.1016/j.ejmech.2020.113059
  • Zhang, Y., Yang, C., Wang, W., Liu, J., Liu, Q., Huang, F., ... Liu, J. (2016). Co-delivery of doxorubicin and curcumin by pH-sensitive prodrug nanoparticle for combination therapy of cancer. Scientific Reports, 6(February), 1-12. https://doi.org/10.1038/srep21225
  • Umapathy, N. S., Ganapathy, V., & Ganapathy, M. E. (2004). Transport of amino acid esters and the amino-acid-based prodrug valganciclovir by the amino acid transporter ATB 0, . Pharmaceutical Research, 21(7), 1303-1310. https://doi.org/10.1023/B:PHAM.0000033019. 49737.28
  • Zhao, N., Francis, N. L., Calvelli, H. R., & Moghe, P. V. (2020). Microglia-targeting nanotherapeutics for neurodegenerative diseases. APL Bioengineering, 4(3). https://doi.org/10.1063/5.0013178
  • Varbanov, H. P., Valiahdi, S. M., Kowol, C. R., Jakupec, M. A., Galanski, M., & Keppler, B. K. (2012). Novel tetracarboxylatoplatinum(iv) complexes as carboplatin prodrugs. Dalton Transactions, 41(47), 14404-14415. https://doi.org/10.1039/c2dt31366a
  • Zhou, J., Zhang, J., David, A. E., & Yang, V. C. (2013). Magnetic tumor targeting of β-glucosidase immobilized iron oxide nanoparticles. Nanotechnology, 24(37). https://doi.org/10.1088/0957- 4484/24/37/375102
  • Wang, W., Wang, S., Liu, T., Ma, Y., Huang, S., Lei, L., ... Ding, Y. (2020). Resveratrol: Multi-Targets Mechanism on Neurodegenerative Diseases Based on Network Pharmacology. Frontiers in Pharmacology, 11(May). https://doi.org/10.3389/fphar.2020.00694
  • Zhu, X., Li, C., Lu, Y., Liu, Y., Wan, D., Zhu, D., ... Ma, G. (2020). Tumor microenvironment-activated therapeutic peptide-conjugated prodrug nanoparticles for enhanced tumor penetration and local T cell activation in the tumor microenvironment. Acta Biomaterialia. https://doi.org/10.1016/j.actbio.2020.11.008
  • Zhang, W., Li, C., Shen, C., Liu, Y., Zhao, X., Liu, Y., ... Yue, C. (2016). Prodrug-based nano-drug delivery system for co-encapsulate paclitaxel and carboplatin for lung cancer treatment. Drug Delivery, 23(7), 2575-2580. https://doi.org/10.3109/10717544.2015.10354 66

Cite this article

APA

    APA : Ashraf, M. S., Rehman, I., & Fatima, U. (2020). Approaches of Prodrug Designing to Treat Cancer, Neurodegenerative Disorders and Viral Diseases. Global Drug Design & Development Review, V(I), 33-47. https://doi.org/10.31703/gdddr.2020(V-I).04

CHICAGO

    CHICAGO : Ashraf, Muhammad Shehzeb, Iqra Rehman, and Urooj Fatima. 2020. "Approaches of Prodrug Designing to Treat Cancer, Neurodegenerative Disorders and Viral Diseases." Global Drug Design & Development Review, V (I): 33-47 doi: 10.31703/gdddr.2020(V-I).04

HARVARD

    HARVARD : ASHRAF, M. S., REHMAN, I. & FATIMA, U. 2020. Approaches of Prodrug Designing to Treat Cancer, Neurodegenerative Disorders and Viral Diseases. Global Drug Design & Development Review, V, 33-47.

MHRA

    MHRA : Ashraf, Muhammad Shehzeb, Iqra Rehman, and Urooj Fatima. 2020. "Approaches of Prodrug Designing to Treat Cancer, Neurodegenerative Disorders and Viral Diseases." Global Drug Design & Development Review, V: 33-47

MLA

    MLA : Ashraf, Muhammad Shehzeb, Iqra Rehman, and Urooj Fatima. "Approaches of Prodrug Designing to Treat Cancer, Neurodegenerative Disorders and Viral Diseases." Global Drug Design & Development Review, V.I (2020): 33-47 Print.

OXFORD

    OXFORD : Ashraf, Muhammad Shehzeb, Rehman, Iqra, and Fatima, Urooj (2020), "Approaches of Prodrug Designing to Treat Cancer, Neurodegenerative Disorders and Viral Diseases", Global Drug Design & Development Review, V (I), 33-47

TURABIAN

    TURABIAN : Ashraf, Muhammad Shehzeb, Iqra Rehman, and Urooj Fatima. "Approaches of Prodrug Designing to Treat Cancer, Neurodegenerative Disorders and Viral Diseases." Global Drug Design & Development Review V, no. I (2020): 33-47. https://doi.org/10.31703/gdddr.2020(V-I).04