166
Views
0
CrossRef citations to date
0
Altmetric
Research Articles

In silico evaluation of pharmacokinetics properties of withanolides and simulation of their biological activities against Alzheimer’s disease

ORCID Icon, ORCID Icon, , , ORCID Icon & ORCID Icon
Pages 2616-2631 | Received 26 Aug 2022, Accepted 19 Apr 2023, Published online: 11 May 2023

References

  • Abraham, M. J., Murtola, T., Schulz, R., P’all, S., Smith, J. C., Hess, B., & Lindahl, E. (2015). Gromacs: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX, 1-2, 19–25. https://doi.org/10.1016/j.softx.2015.06.001
  • Almeida, A. A., Cota, B. B., Rodrigues, L. A., Dutra, L. L., Kohlhoff, M., Bressan, G. C., Brandão, G. C., & Leite, J. P. V. (2022). Withalutin, a new cytotoxic withanolide from athenaea velutina (sendtn.) d’arcy. Natural Product Research, 36(24), 6304–6311. https://doi.org/10.1080/14786419.2022.2039135
  • Almeida-Lafet’a, R. C., Ferreira, M. J., Emerenciano, V. P., & Kaplan, M. A. (2010). Withanolides from aureliana fasciculata var. fasciculata. Helvetica Chimica Acta, 93(12), 2478–2487. https://doi.org/10.1002/hlca.201000126
  • Ambure, P., Bhat, J., Puzyn, T., & Roy, K. (2019). Identifying natural compounds as multi-target-directed ligands against alzheimer’s disease: An in silico approach. Journal of Biomolecular Structure & Dynamics, 37(5), 1282–1306. https://doi.org/10.1080/07391102.2018.1456975
  • Baig, M. W., Nasir, B., Waseem, D., Majid, M., Khan, M. Z. I., & Haq, I.-u. (2020). Withametelin: A biologically active withanolide in cancer, inflammation, pain and depression. Saudi Pharmaceutical Journal: SPJ: The Official Publication of the Saudi Pharmaceutical Society, 28(12), 1526–1537. https://doi.org/10.1016/j.jsps.2020.09.021
  • Berendsen, H. J., Postma, J. P., van Gunsteren, W. F., & Hermans, J. (1981). Interaction models for water in relation to protein hydration. In Intermolecular forces (pp. 331–342). Springer.
  • Berthold, M. R., Cebron, N., Dill, F., Gabriel, T. R., K¨otter, T., Meinl, T., Ohl, P., Thiel, K., & Wiswedel, B. (2009). Knime-the konstanz information miner: Version 2.0 and beyond. ACM SIGKDD Explorations Newsletter, 11(1), 26–31. https://doi.org/10.1145/1656274.1656280
  • Binda, C., Wang, J., Pisani, L., Caccia, C., Carotti, A., Salvati, P., Edmondson, D. E., & Mattevi, A. (2007). Structures of human monoamine oxidase b complexes with selective noncovalent inhibitors: Safinamide and coumarin analogs. Journal of Medicinal Chemistry, 50(23), 5848–5852. https://doi.org/10.1021/jm070677y
  • Castro, S. J., Casero, C. N., Padr’on, J. M., & Nicotra, V. E. (2019). Selective antiproliferative withanolides from species in the genera eriolarynx and deprea. Journal of Natural Products, 82(5), 1338–1344. https://doi.org/10.1021/acs.jnatprod.9b00117
  • Chen, C. Y.-C. (2011). Tcm database@ taiwan: The world’s largest traditional chinese medicine database for drug screening in silico. PloS One, 6(1), e15939. https://doi.org/10.1371/journal.pone.0015939
  • Chen, L.-X., He, H., & Qiu, F. (2011). Natural withanolides: An overview. Natural Product Reports, 28(4), 705–740. https://doi.org/10.1039/c0np00045k
  • Choudhary, M. I., Yousuf, S., Nawaz, S. A., Ahmed, S., & Atta-Ur-Rahman. (2004). Cholinesterase inhibiting withanolides from withania somnifera. Chemical & Pharmaceutical Bulletin, 52(11), 1358–1361. https://doi.org/10.1248/cpb.52.1358
  • Crane, E. A., Heydenreuter, W., Beck, K. R., Strajhar, P., Vomacka, J., Smiesko, M., Mons, E., Barth, L., Neuburger, M., Vedani, A., Odermatt, A., Sieber, S. A., & Gademann, K. (2019). Profiling withanolide a for therapeutic targets in neurodegenerative diseases. Bioorganic & Medicinal Chemistry, 27(12), 2508–2520. https://doi.org/10.1016/j.bmc.2019.03.022
  • Cummings, J. L., Goldman, D. P., Simmons-Stern, N. R., & Ponton, E. (2022). The costs of developing treatments for alzheimer’s disease: A retrospective exploration. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 18(3), 469–477. https://doi.org/10.1002/alz.12450
  • Daina, A., Michielin, O., & Zoete, V. (2017). Swissadme: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7(1), 1–13. https://doi.org/10.1038/srep42717
  • Daina, A., & Zoete, V. (2016). A boiled-egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem, 11(11), 1117–1121. https://doi.org/10.1002/cmdc.201600182
  • Das, R., Rauf, A., Akhter, S., Islam, M. N., Emran, T. B., Mitra, S., Khan, IN., & Mubarak, M. S. (2021). Role of withaferin a and its derivatives in the management of alzheimer’s disease: Recent trends and future perspectives. Molecules, 26(12), 3696. https://doi.org/10.3390/molecules26123696
  • Deanna, R., Larter, M. D., Barboza, G. E., & Smith, S. D. (2019). Repeated evolution of a morphological novelty: A phylogenetic analysis of the inflated fruiting calyx in the physalideae tribe (solanaceae). American Journal of Botany, 106(2), 270–279. https://doi.org/10.1002/ajb2.1242
  • Devkar, S. T., Kandhare, A. D., Sloley, B. D., Jagtap, S. D., Lin, J., Tam, Y. K., Katyare, S. S., Bodhankar, S. L., & Hegde, M. V. (2015). Evaluation of the bioavailability of major withanolides of withania somnifera using an in vitro absorption model system. Journal of Advanced Pharmaceutical Technology & Research, 6(4), 159–164. https://doi.org/10.4103/2231-4040.165023
  • Dhar, N., Razdan, S., Rana, S., Bhat, W. W., Vishwakarma, R., & Lattoo, S. K. (2015). A decade of molecular understanding of withanolide biosynthesis and in vitro studies in withania somnifera (l.) dunal: Prospects and perspectives for pathway engineering. Frontiers in Plant Science, 6, 1031. https://doi.org/10.3389/fpls.2015.01031
  • Dolinsky, T. J., Nielsen, J. E., McCammon, J. A., & Baker, N. A. (2004). Pdb2pqr: An automated pipeline for the setup of poisson–boltzmann electrostatics calculations. Nucleic Acids Research, 32(Web Server), W665–W667. https://doi.org/10.1093/nar/gkh381
  • Du, X., Wang, X., & Geng, M. (2018). Alzheimer’s disease hypothesis and related therapies. Translational Neurodegeneration, 7(1), 2. https://doi.org/10.1186/s40035-018-0107-y
  • Ganesan, A. (2008). The impact of natural products upon modern drug discovery. Current Opinion in Chemical Biology, 12(3), 306–317. https://doi.org/10.1016/j.cbpa.2008.03.016
  • Gobbo, D., Piretti, V., Di Martino, R. M. C., Tripathi, S. K., Giabbai, B., Storici, P., Demitri, N., Girotto, S., Decherchi, S., & Cavalli, A. (2019). Investigating drug–target residence time in kinases through enhanced sampling simulations. Journal of Chemical Theory and Computation, 15(8), 4646–4659. https://doi.org/10.1021/acs.jctc.9b00104
  • Hampel, H., Mesulam, M.-M., Cuello, A. C., Khachaturian, A. S., Vergallo, A., Farlow, M., Snyder, P., Giacobini, E., & Khachaturian, Z. (2019). Revisiting the cholinergic hypothesis in alzheimer’s disease: Emerging evidence from translational and clinical research. The Journal of Prevention of Alzheimer’s Disease, 6(1), 2–15. https://doi.org/10.14283/jpad.2018.43
  • Hsieh, P.-W., Huang, Z.-Y., Chen, J.-H., Chang, F.-R., Wu, C.-C., Yang, Y.-L., Chiang, M. Y., Yen, M.-H., Chen, S.-L., Yen, H.-F., Lübken, T., Hung, W.-C., & Wu, Y.-C. (2007). et al.: Cytotoxic withanolides from tubocapsicum anomalum. Journal of Natural Products, 70(5), 747–753. https://doi.org/10.1021/np0605541
  • Huang, J., Rauscher, S., Nawrocki, G., Ran, T., Feig, M., De Groot, B. L., Grubmüller, H., & MacKerell, A. D. (2017). Charmm36m: An improved force field for folded and intrinsically disordered proteins. Nature Methods, 14(1), 71–73. https://doi.org/10.1038/nmeth.4067
  • Iserloh, U., Wu, Y., Cumming, J. N., Pan, J., Wang, L. Y., Stamford, A. W., Kennedy, M. E., Kuvelkar, R., Chen, X., Parker, E. M., Strickland, C., & Voigt, J. (2008). Potent pyrrolidine-and piperidine-based bace-1 inhibitors. Bioorganic & Medicinal Chemistry Letters, 18(1), 414–417. https://doi.org/10.1016/j.bmcl.2007.10.116
  • Jo, S., Kim, T., Iyer, V. G., & Im, W. (2008). CHARMM-GUI: A web-based graphical user interface for CHARMM. Journal of computational chemistry, 1859–1865. https://doi.org/10.1002/jcc.20945
  • Khan, S. A., Khan, S. B., Shah, Z., & Asiri, A. M. (2016). Withanolides: Biologically active constituents in the treatment of alzheimer’s disease. Medicinal Chemistry (Shariqah (United Arab Emirates)), 12(3), 238–256. https://doi.org/10.2174/1573406411666151030112314
  • Khanal, P., Chikhale, R., Dey, Y. N., Pasha, I., Chand, S., Gurav, N., Ayyanar, M., Patil, B., & Gurav, S. (2022). Withanolides from withania somnifera as an immunity booster and their therapeutic options against covid-19. Journal of Biomolecular Structure and Dynamics, 40(12), 1–14.
  • Kryger, G., Silman, I., & Sussman, J. L. (1999). Structure of acetylcholinesterase complexed with e2020 (aricept®): Implications for the design of new antialzheimer drugs. Structure (London, England: 1993), 7(3), 297–307. https://doi.org/10.1016/s0969-2126(99)80040-9
  • Kumar, V., Faheem, M., & Lee, K. W. (2021). A decade of machine learningbased predictive models for human pharmacokinetics: Advances and challenges. Drug Discovery Today, 27(2), 529–537.
  • Kumar, S., Seal, C. J., Howes, M., Kite, G. C., & Okello, E. J. (2010). In vitro protective effects of withania somnifera (l.) dunal root extract against hydrogen peroxide and β-amyloid (1–42)-induced cytotoxicity in differentiated pc12 cells. Phytotherapy Research : PTR, 24(10), 1567–1574. https://doi.org/10.1002/ptr.3261
  • Liebeschuetz, J. W., Cole, J. C., & Korb, O. (2012). Pose prediction and virtual screening performance of GOLD scoring functions in a standardized test. Journal of Computer-Aided Molecular Design, 26(6), 737–748. https://doi.org/10.1007/s10822-012-9551-4
  • Liu, Y. (2022). In silico evaluation of pharmacokinetics and acute toxicity of withanolides in ashawagandha. Phytochemistry Letters, 47, 130–135. https://doi.org/10.1016/j.phytol.2021.12.007
  • Mahrous, R., Ghareeb, D. A., Fathy, H. M., EL-Khair, R. M. A., & Omar, A. A. (2017). The protective effect of egyptian withania somnifera against alzheimer’s. Medicinal & Aromatic Plants, 6(285), 2167.
  • Makhoba, X. H., Viegas, C., Jr, Mosa, R. A., Viegas, F. P., & Pooe, O. J. (2020). Potential impact of the multi-target drug approach in the treatment of some complex diseases. Drug Design, Development and Therapy, 14, 3235–3249. https://doi.org/10.2147/DDDT.S257494
  • Malmström, J., Viklund, J., Slivo, C., Costa, A., Maudet, M., Sandelin, C., Hiller, G., Olsson, L.-L., Aagaard, A., Geschwindner, S., Xue, Y., & Vasänge, M. (2012). Synthesis and structure-activity relationship of 4-(1, 3-benzothiazol-2yl)-thiophene-2-sulfonamides as cyclin-dependent kinase 5 (cdk5)/p25 inhibitors. Bioorganic & Medicinal Chemistry Letters, 22(18), 5919–5923. https://doi.org/10.1016/j.bmcl.2012.07.068
  • Misico, R. I., Nicotra, V. E., Oberti, J. C., Barboza, G., Gil, R. R., & Burton, G. (2011). Withanolides and related steroids. Progress in the Chemistry of Organic Natural Products, 94, 127–229.
  • Newman, D. J., & Cragg, G. M. (2020). Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. Journal of Natural Products, 83(3), 770–803. https://doi.org/10.1021/acs.jnatprod.9b01285
  • Olmstead, R. G., Bohs, L., Migid, H. A., Santiago-Valentin, E., Garcia, V. F., & Collier, S. M. (2008). A molecular phylogeny of the solanaceae. Taxon, 57(4), 1159–1181. https://doi.org/10.1002/tax.574010
  • Olsson, M. H., Søndergaard, C. R., Rostkowski, M., & Jensen, J. H. (2011). Propka3: Consistent treatment of internal and surface residues in empirical p k a predictions. Journal of Chemical Theory and Computation, 7(2), 525–537. https://doi.org/10.1021/ct100578z
  • Ovais, M., Zia, N., Ahmad, I., Khalil, A. T., Raza, A., Ayaz, M., Sadiq, A., Ullah, F., & Shinwari, Z. K. (2018). Phyto-therapeutic and nanomedicinal approaches to cure alzheimer’s disease: Present status and future opportunities. Frontiers in Aging Neuroscience, 10, 284. https://doi.org/10.3389/fnagi.2018.00284
  • Pantaleão, S. Q., Fernandes, P. O., Gonçalves, J. E., Maltarollo, V. G., & Honorio, K. M. (2022). Recent advances in the prediction of pharmacokinetics properties in drug design studies: A review. ChemMedChem, 17(1), 202100542. https://doi.org/10.1002/cmdc.202100542
  • Parrinello, M., & Rahman, A. (1982). Strain fluctuations and elastic constants. The Journal of Chemical Physics, 76(5), 2662–2666. https://doi.org/10.1063/1.443248
  • Patil, S. P., Maki, S., Khedkar, S. A., Rigby, A. C., & Chan, C. (2010). Withanolide a and asiatic acid modulate multiple targets associated with amyloid-β precursor protein processing and amyloid-β protein clearance. Journal of Natural Products, 73(7), 1196–1202. https://doi.org/10.1021/np900633j
  • Pil’on-Jim’enez, B. A., Sald’ıvar-Gonz’alez, F. I., D’ıaz-Eufracio, B. I., & MedinaFranco, J. L. (2019). Biofacquim: A mexican compound database of natural products. Biomolecules, 9(1), 31.
  • Pilon, A. C., Valli, M., Dametto, A. C., Pinto, M. E. F., Freire, R. T., Castro-Gamboa, I., Andricopulo, A. D., & Bolzani, V. S. (2017). Nubbedb: An updated database to uncover chemical and biological information from brazilian biodiversity. Scientific Reports, 7(1), 1–12. https://doi.org/10.1038/s41598-017-07451-x
  • Pires, D. E., Blundell, T. L., & Ascher, D. B. (2015). pkcsm: Predicting smallmolecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of Medicinal Chemistry, 58(9), 4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104
  • Ramsay, R. R., Popovic-Nikolic, M. R., Nikolic, K., Uliassi, E., & Bolognesi, M. L. (2018). A perspective on multi-target drug discovery and design for complex diseases. Clinical and Translational Medicine, 7(1), 1–14. https://doi.org/10.1186/s40169-017-0181-2
  • Rosenberry, T. L., Brazzolotto, X., Macdonald, I. R., Wandhammer, M., Trovaslet-Leroy, M., Darvesh, S., & Nachon, F. (2017). Comparison of the binding of reversible inhibitors to human butyrylcholinesterase and acetylcholinesterase: A crystallographic, kinetic and calorimetric study. Molecules, 22(12), 2098. https://doi.org/10.3390/molecules22122098
  • Saslis-Lagoudakis, C. H., Savolainen, V., Williamson, E. M., Forest, F., Wagstaff, S. J., Baral, S. R., Watson, M. F., Pendry, C. A., & Hawkins, J. A. (2012). Phylogenies reveal predictive power of traditional medicine in bioprospecting. Proceedings of the National Academy of Sciences of the United States of America, 109(39), 15835–15840. https://doi.org/10.1073/pnas.1202242109
  • Schirmer Pigatto, A. G., Mentz, L. A., Gon, G., & Calves Soares, L. (2014). Chemotaxonomic characterization and chemical similarity of tribes/genera of the solanoideae subfamily (solanaceae) based on occurrence of withanolides. Biochemical Systematics and Ecology, 54, 40–47. https://doi.org/10.1016/j.bse.2013.12.026
  • Sehgal, N., Gupta, A., Valli, R. K., Joshi, S. D., Mills, J. T., Hamel, E., Khanna, P., Jain, S. C., Thakur, S. S., & Ravindranath, V. (2012). Withania somnifera reverses alzheimer’s disease pathology by enhancing low-density lipoprotein receptor-related protein in liver. Proceedings of the National Academy of Sciences, 109(9), 3510–3515. https://doi.org/10.1073/pnas.1112209109
  • Simoben, C. V., Qaseem, A., Moumbock, A. F., Telukunta, K. K., Günther, S., Sippl, W., & Ntie-Kang, F. (2020). Pharmacoinformatic investigation of medicinal plants from East Africa. Molecular Informatics, 39(11), 2000163. https://doi.org/10.1002/minf.202000163
  • Sonar, V. P., Fois, B., Distinto, S., Maccioni, E., Meleddu, R., Cottiglia, F., Acquas, E., Kasture, S., Floris, C., Colombo, D., Sissi, C., Sanna, E., & Talani, G. (2019). Ferulic acid esters and withanolides: in search of withania somnifera gabaa receptor modulators. Journal of Natural Products, 82(5), 1250–1257. https://doi.org/10.1021/acs.jnatprod.8b01023
  • Torres, P. H., Sodero, A. C., Jofily, P., & Silva, Jr, F. P. (2019). Key topics in molecular docking for drug design. International Journal of Molecular Sciences, 20(18), 4574. https://doi.org/10.3390/ijms20184574
  • Valdés-Tresanco, M. S., Valdés-Tresanco, M. E., Valiente, P. A., & Moreno, E. (2021). gmx_MMPBSA: A new tool to perform end-state free energy calculations with GROMACS. Journal of Chemical Theory and Computation, 17(10), 6281–6291. https://doi.org/10.1021/acs.jctc.1c00645
  • Veríssimo, G. C., dos Santos Júnior, V. S., de Almeida, I., Ruas, M. S. M., Coutinho, L. G., de Oliveira, R. B., Alves, R. J., & Maltarollo, V. G. (2022). The brazilian compound library (bracoli) database: A repository of chemical and biological information for drug design. Molecular Diversity, 26, 1–11.
  • Wishart, D. S., Feunang, Y. D., Guo, A. C., Lo, E. J., Marcu, A., Grant, J. R., Sajed, T., Johnson, D., Li, C., Sayeeda, Z., Assempour, N., Iynkkaran, I., Liu, Y., Maciejewski, A., Gale, N., Wilson, A., Chin, L., Cummings, R., Le, D., … Wilson, M. (2018). Drugbank 5.0: A major update to the drugbank database for 2018. Nucleic Acids Research, 46(D1), D1074–D1082. https://doi.org/10.1093/nar/gkx1037
  • Xia, G-y., Cao, S-j., Chen, L-x., & Qiu, F. (2022). Natural withanolides, an update. Natural Product Reports, 39(4), 784–813. https://doi.org/10.1039/D1NP00055A
  • Xiang, K., Li, C., Li, M.-X., Song, Z.-R., Ma, X.-X., Sun, D.-J., Li, H., & Chen, L.-X. (2021). Withanolides isolated from tubocapsicum anomalum and their antiproliferative activity. Bioorganic Chemistry, 110, 104809. https://doi.org/10.1016/j.bioorg.2021.104809
  • Xiong, G., Wu, Z., Yi, J., Fu, L., Yang, Z., Hsieh, C., Yin, M., Zeng, X., Wu, C., Lu, A., Chen, X., Hou, T., & Cao, D. (2021). Admetlab 2.0: An integrated online platform for accurate and comprehensive predictions of admet properties. Nucleic Acids Research, 49(W1), W5–W14. https://doi.org/10.1093/nar/gkab255
  • Zeiger, E. (2019). The test that changed the world: The ames test and the regulation of chemicals. Mutation Research. Genetic Toxicology and Environmental Mutagenesis, 841, 43–48. https://doi.org/10.1016/j.mrgentox.2019.05.007
  • Zhang, M.-Q., & Wilkinson, B. (2007). Drug discovery beyond the ‘rule-of-five. Current Opinion in Biotechnology, 18(6), 478–488. https://doi.org/10.1016/j.copbio.2007.10.005

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.