Pharmacokinetic Studies of Curcumin Based Pyrazoline MAO Inhibitors
Published: November 17, 2020
Authors
- Vishnu Nayak Badavath
- Venkatesan Jayaprakash
- Susanta Kumar Mondal
- Sandeep Arora
- Orlando Acevedo
- Abhishek Thakur
- Rajasekhara Reddy Iska
Keywords
Structure-based-drug design, Curcumin based Pyrazoline analogues, Ferulic acid amides, MDCK-II permeability studies, Liver microsomal metabolic stability studies
Abstract
Background: Curcumin is a natural phenolic compound obtained from Curcuma longa, with proven human monoamine oxidase (MAO) inhibitory activity, but due to its poor oral bioavailability, blood-brain barrier permeability and extensive metabolism in the liver, it has never been recognized as a drug candidate.
Purpose: In this study, the structure-based-drug design (SBDD) was adopted to incorporate the structural features of Curcumin with an aim to improve drug permeability and metabolic stability.
Method: A series of ferulic amides (half portion of curcumin) (1-3) and curcumin based pyrazolinescompounds (4-6) were designed and Curcumintested for their membrane permeability and liver microsomal metabolic stability in a various animal in an in-vitro assay system.
Conclusion: All the designed compounds showed a significant enhancement in permeability and metabolic stability is achieved through chemical modification.
References
- Badavath, V. N., & Jayaprakash, V. (2021). MAO Inhibitory Activity Of 4, 5-Dihydro-1 H-Pyrazole Derivatives: A Platform To Design Novel Antidepressants. Frontiers in Drug Design & Discovery, 10, 47-91. https://doi.org/10.2174/9789811421563121100005
- Badavath, V. N., Baysal, I., Uçar, G., Mondal, S. K., Sinha, B. N., & Jayaprakash, V. (2016). Monoamine Oxidase Inhibitory Activity of Ferulic Acid Amides: Curcumin- Based Design and Synthesis. Archiv der Pharmazie, 349(1), 9-19. https://doi.org/10.1002/ardp.201500317
- Badavath, V. N., Baysal, I., Ucar, G., Sinha, B. N., & Jayaprakash, V. (2016). Monoamine Oxidase Inhibitory Activity of Novel Pyrazoline Analogues: Curcumin Based Design and Synthesis. ACS Medicinal Chemistry Letters, 7(1), 56-61. https://doi.org/10.1021/acsmedchemlett.5b00326
- Badavath, V. N., Jadav, S. S., Pastorino, B., de Lamballerie, X., Sinha, B. N., & Jayaprakash, V. (2016). Synthesis and Antiviral Activity of 2-aryl-4H-chromen-4-one Derivatives Against Chikungunya Virus. Letters in Drug Design & Discovery, 13(10), 1019-1024. https://doi.org/10.2174/1570180813666160711163 349
- Badavath, V. N., Nath, C., Ganta, N. M., Ucar, G., Sinha, B. N., & Jayaprakash, V. (2017). Design, synthesis and MAO inhibitory activity of 2-(arylmethylidene)-2, 3-dihydro-1-benzofuran-3-one derivatives. Chinese Chemical Letters, 28(7), 1528-1532. https://doi.org/10.1016/j.cclet.2017.02.009
- Badavath, V. N., Ucar, G., Sinha, B. N., Mondal, S. K., & Jayaprakash, V. (2016). Monoamine Oxidase Inhibitory Activity of Novel Pyrazoline Analogues: Curcumin Based Design and Synthesis-II. Chemistry Select, 1(18), 5879-5884. https://doi.org/10.1002/slct.201600914
- Dagar, P., Dahiya, P., & Bhambi, M. (2014). Recent advances in curcumin nanoformulations. Nano Science & Nano Technology: An Indian Journal, 8(12), 458-474.
- Di, L., et al. (2003). Optimization of a higher throughput microsomal stability screening assay for profiling drug discovery candidates. Journal of Biomolecular Screening, 8(4), 453-462. https://doi.org/10.1177/1087057103255988
- Di, L., et al. (2011). Development of a new permeability assay using low‐efflux MDCKII cells. Journal of Pharmaceutical Sciences, 100(11), 4974-4985. https://doi.org/10.1002/jps.22674
- Irvine, J. D., Takahashi, L., Lockhart, K., Cheong, J., Tolan, J. W., Selick, H. E., & Grove, J. R. (1999). MDCK (Madin-Darby canine kidney) cells: a tool for membrane permeability screening. Journal of Pharmaceutical Sciences, 88(1), 28-33. https://doi.org/10.1021/js9803205
- Jadav, S. S., et al. (2015). Design, synthesis, optimization and antiviral activity of a class of hybrid dengue virus E protein inhibitors. Bioorganic and Medicinal Chemistry Letters, 28(8), 1747-1752. https://doi.org/10.1016/j.bmcl.2015.02.059
- Kellard, L., & Engelstein, M. (2007). Automation of cell-based and non cell-based permeability assays. Journal of the Association for Laboratory Automation, 12(2), 104-109. https://doi.org/10.1016/j.jala.2006.10.008
- Mondal, S. K., Mazumdar, U. K., Mondal, N. B., & Banerjee, S. (2008). Optimization of rat liver microsomal stability assay using HPLC. Journal of Biological Sciences, 8(6), 1110-1114. https://doi.org/10.3923/jbs.2008.1110.1114
- Narender, T., Venkateswarlu, K., Nayak, B. V., & Sarkar, S. (2011). A new chemical access for 3’-acetyl-4’-hydroxychalcones using borontrifluoride-etherate via a regionselective Claisen-Schmidt condensation and its application in the synthesis of chalcone hybrids. Tetrahedron Letters, 52(44), 5794-5798. https://doi.org/10.1016/j.tetlet.2011.08.120
- Nath, C., Badavath, V. N., Thakur, A., Ucar, G., Acevedo, O., Mohd Siddique, M. U., & Jayaprakash, V. (2018). Curcumin-based pyrazoline analogues as selective inhibitors of human monoamine oxidase A. MedChemComm., 9(7), 1164-1171. https://doi.org/10.1039/C8MD00196K
- Nayak, B. V., Ciftci-Yabanoglu, S., Bhakat, S., Timiri, A. K., Sinha, B. N., Ucar, G., Soliman, M. E. S., & Jayaprakash, V. (2015). Monoamine oxidase inhibitory activity of 2-aryl-4H-chromen-4-ones. Bioorganic Chemistry, 58, 72-80. https://doi.org/10.1016/j.bioorg.2014.11.008
- Nayak, B. V., Ciftci-Yabanoglu, S., Jadav, S. S., Jagrat, M., Sinha, B. N., Ucar, G., & Jayaprakash, V. (2013). Monoamine oxidase inhibitory activity of 3, 5-biaryl-4, 5-dihydro-1H- pyrazole-1-carboxylate derivatives. European Journal of Medicinal Chemistry, 69, 762-767. https://doi.org/10.1016/j.ejmech.2013.09.010
- Pan, M. -H., Huang, T. -M., & Lin, J. -K. (1999). Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metabolism and Disposition, 27(4), 486-494.
- Prasad, S., Tyagi, A. K., & Aggarwal, B. B. (2014). Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: The golden pigment from golden spice. Cancer Research and Treatment , 46(1), 2-18. https://doi.org/10.4143/crt.2014.46.1.2
- Singh, P. K., Wani, K., Kaul-Ghanekar, R., Prabhune, A., & Ogale, S. (2014). From micron to nano-curcumin by sophorolipid co-processing: highly enhanced bioavailability, fluorescence, and anti-cancer efficacy. RSC Advances, 4(104), 60334-60341. https://doi.org/10.1039/C4RA07300B
- Wahlang, B., Pawar, Y. B., & Bansal, A. K. (2011). Identification of permeability-related hurdles in oral delivery of curcumin using the Caco-2 cell model. European Journal of Pharmaceutics and Biopharmaceutics, 77(2), 275-282. https://doi.org/10.1016/j.ejpb.2010.12.006
- Yallapu, M. M., Jaggi, M., & Chauhan, S. C. (2012). Curcumin nanoformulations: a future nanomedicine for cancer. Drug Discovery Today, 17(1-2), 71-80. https://doi.org/10.1016/j.drudis.2011.09.009
- Yasmin, S., et al. (2020). A Series of Ferulic Acid Amides Reveals Unexpected Peroxiredoxin 1Inhibitory Activity with in vivo Antidiabetic and Hypolipidemic Effects. ChemMedChem, 15, 1-16. https://doi.org/10.1002/cmdc.202000564
How to Cite
Vishnu Nayak Badavath , Venkatesan Jayaprakash, Susanta Kumar Mondal, Sandeep Arora, Orlando Acevedo, Abhishek Thakur, and Rajasekhara Reddy Iska. Pharmacokinetic Studies of Curcumin Based Pyrazoline MAO Inhibitors.
J. Pharm. Technol. Res. Manag.. 2020, 08, 85-89
