Insights into the potential of withanolides as Phosphodiesterase-4 (PDE4D) inhibitors

References

• Azevedo, M. F., Faucz, F. R., Bimpaki, E., Horvath, A., Levy, I., de Alexandre, R. B., Ahmad, F., Manganiello, V., & Stratakis, C. A. (2014). Clinical and molecular genetics of the phosphodiesterases (PDEs). Endocrine Reviews, 35(2), 195–233. https://doi.org/10.1210/er.2013-1053
   PubMed Web of Science ®Google Scholar
• Balbach, M., Beckert, V., Hansen, J. N., & Wachten, D. (2018). Shedding light on the role of cAMP in mammalian sperm physiology. Molecular and Cellular Endocrinology, 468, 111–120. https://doi.org/10.1016/j.mce.2017.11.008
   PubMed Web of Science ®Google Scholar
• Cai, Y.-H., Guo, Y., Li, Z., Wu, D., Li, X., Zhang, H., Yang, J., Lu, H., Sun, Z., Luo, H.-B., Yin, S., & Wu, Y. (2016). Discovery and modelling studies of natural ingredients from Gaultheria yunnanensis (FRANCH.) against phosphodiesterase-4. European Journal of Medicinal Chemistry, 114, 134–140. https://doi.org/10.1016/j.ejmech.2015.12.002
   PubMed Web of Science ®Google Scholar
• Chen, S.-K., Zhao, P., Shao, Y.-X., Li, Z., Zhang, C., Liu, P., He, X., Luo, H.-B., & Hu, X. (2012). Moracin M from Morus alba L. is a natural phosphodiesterase-4 inhibitor. Bioorganic & Medicinal Chemistry Letters, 22(9), 3261–3264. https://doi.org/10.1016/j.bmcl.2012.03.026
   PubMed Web of Science ®Google Scholar
• Daina, A., Michielin, O., & Zoete, V. (2019). SwissTargetPrediction: Updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Research, 47(W1), W357–W364. https://doi.org/10.1093/nar/gkz382
   PubMed Web of Science ®Google Scholar
• Delhaye, S., & Bardoni, B. (2021). Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders. Molecular Psychiatry, 26(9), 4570–4582. https://doi.org/10.1038/s41380-020-00997-9
   PubMed Web of Science ®Google Scholar
• Dhanjal, J. K., Kumar, V., Garg, S., Subramani, C., Agarwal, S., Wang, J., Zhang, H., Kaul, A., Kalra, R. S., Kaul, S. C., Vrati, S., Sundar, D., & Wadhwa, R. (2021). Molecular mechanism of anti-SARS-CoV2 activity of Ashwagandha-derived withanolides. International Journal of Biological Macromolecules, 184, 297–312. https://doi.org/10.1016/j.ijbiomac.2021.06.015
   PubMed Web of Science ®Google Scholar
• Dyke, H. J., & Montana, J. G. (2002). Update on the therapeutic potential of PDE4 inhibitors. Expert Opinion on Investigational Drugs, 11(1), 1–13. https://doi.org/10.1517/13543784.11.1.1
   PubMed Web of Science ®Google Scholar
• Evenou, J.-P., Wagner, J., Zenke, G., Brinkmann, V., Wagner, K., Kovarik, J., Welzenbach, K. A., Weitz-Schmidt, G., Guntermann, C., Towbin, H., Cottens, S., Kaminski, S., Letschka, T., Lutz-Nicoladoni, C., Gruber, T., Hermann-Kleiter, N., Thuille, N., & Baier, G. (2009). The potent protein kinase C-selective inhibitor AEB071 (sotrastaurin) represents a new class of immunosuppressive agents affecting early T-cell activation. The Journal of Pharmacology and Experimental Therapeutics, 330(3), 792–801. https://doi.org/10.1124/jpet.109.153205
   PubMed Web of Science ®Google Scholar
• Fajardo, A. M., Piazza, G. A., & Tinsley, H. N. (2014). The role of cyclic nucleotide signaling pathways in cancer: Targets for prevention and treatment. Cancers, 6(1), 436–458. https://doi.org/10.3390/cancers6010436
   PubMed Web of Science ®Google Scholar
• Freitas, M. J., Vijayaraghavan, S., & Fardilha, M. (2017). Signaling mechanisms in mammalian sperm motility. Biology of Reproduction, 96(1), 2–12. https://doi.org/10.1095/biolreprod.116.144337
   PubMed Web of Science ®Google Scholar
• Géczy, T., Oláh, A., Tóth, B. I., Czifra, G., Szöllősi, A. G., Szabó, T., Zouboulis, C. C., Paus, R., & Bíró, T. (2012). Protein kinase C isoforms have differential roles in the regulation of human sebocyte biology. The Journal of Investigative Dermatology, 132(8), 1988–1997. https://doi.org/10.1038/jid.2012.94
   PubMed Web of Science ®Google Scholar
• Genheden, S., & Ryde, U. (2015). The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities. Expert Opinion on Drug Discovery, 10(5), 449–461. https://doi.org/10.1517/17460441.2015.1032936
   PubMed Web of Science ®Google Scholar
• Goldhoff, P., Warrington, N. M., Limbrick, D. D., Hope, A., Woerner, B. M., Jackson, E., Perry, A., Piwnica-Worms, D., & Rubin, J. B. (2008). Targeted inhibition of cyclic AMP phosphodiesterase-4 promotes brain tumor regression. Clinical Cancer Research, 14(23), 7717–7725. https://doi.org/10.1158/1078-0432.CCR-08-0827
   PubMed Web of Science ®Google Scholar
• Hsien Lai, S., Zervoudakis, G., Chou, J., Gurney, M. E., & Quesnelle, K. M. (2020). PDE4 subtypes in cancer. Oncogene, 39(19), 3791–3802. https://doi.org/10.1038/s41388-020-1258-8
   PubMed Web of Science ®Google Scholar
• Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W., & Klein, M. L. (1983). Comparison of simple potential functions for simulating liquid water. The Journal of Chemical Physics, 79(2), 926–935. https://doi.org/10.1063/1.445869
   Web of Science ®Google Scholar
• Kalra, R. S., Kumar, V., Dhanjal, J. K., Garg, S., Li, X., Kaul, S. C., … Wadhwa, R. (2021). COVID19-inhibitory activity of withanolides involves targeting of the host cell surface receptor ACE2: Insights from computational and biochemical assays. Journal of Biomolecular Structure and Dynamics, 1–14. https://doi.org/10.1080/07391102.2021.1902858
   Google Scholar
• Khanal, P., Chikhale, R., Dey, Y. N., Pasha, I., Chand, S., Gurav, N., Ayyanar, M., Patil, B. M., & Gurav, S. (2021). Withanolides from Withania somnifera as an immunity booster and their therapeutic options against COVID-19. Journal of Biomolecular Structure and Dynamics, 1–14. https://doi.org/10.1080/07391102.2020.1869588
   Google Scholar
• Kolosionek, E., Savai, R., Ghofrani, H. A., Weissmann, N., Guenther, A., Grimminger, F., Seeger, W., Banat, G. A., Schermuly, R. T., & Pullamsetti, S. S. (2009). Expression and activity of phosphodiesterase isoforms during epithelial mesenchymal transition: The role of phosphodiesterase 4. Molecular Biology of the Cell, 20(22), 4751–4765. https://doi.org/10.1091/mbc.E09-01-0019
   PubMed Web of Science ®Google Scholar
• Laskowski, R. A., Rullmannn, J. A., MacArthur, M. W., Kaptein, R., & Thornton, J. M. (1996). AQUA and PROCHECK-NMR: Programs for checking the quality of protein structures solved by NMR. Journal of Biomolecular NMR, 8(4), 477–486. https://doi.org/10.1007/BF00228148
   PubMed Web of Science ®Google Scholar
• Lee, M. E., Markowitz, J., Lee, J. O., & Lee, H. (2002). Crystal structure of phosphodiesterase 4D and inhibitor complex(1). FEBS Letters, 530(1–3), 53–58. https://doi.org/10.1016/S0014-5793(02)03396-3
   PubMed Web of Science ®Google Scholar
• Levy, I., Horvath, A., Azevedo, M., de Alexandre, R. B., & Stratakis, C. A. (2011). Phosphodiesterase function and endocrine cells: Links to human disease and roles in tumor development and treatment. Current Opinion in Pharmacology, 11(6), 689–697. https://doi.org/10.1016/j.coph.2011.10.003
   PubMed Web of Science ®Google Scholar
• Li, H., Zuo, J., & Tang, W. (2018). Phosphodiesterase-4 inhibitors for the treatment of inflammatory diseases. Frontiers in Pharmacology, 9, 1048. https://doi.org/10.3389/fphar.2018.01048
   PubMed Web of Science ®Google Scholar
• Lin, D.-C., Xu, L., Ding, L.-W., Sharma, A., Liu, L.-Z., Yang, H., Tan, P., Vadgama, J., Karlan, B. Y., Lester, J., Urban, N., Schummer, M., Doan, N., Said, J. W., Sun, H., Walsh, M., Thomas, C. J., Patel, P., Yin, D., Chan, D., & Koeffler, H. P. (2013). Genomic and functional characterizations of phosphodiesterase subtype 4D in human cancers. Proceedings of the National Academy of Sciences of the United States of America, 110(15), 6109–6114. https://doi.org/10.1073/pnas.1218206110
   PubMed Web of Science ®Google Scholar
• Lipinski, C. A. (2000). Drug-like properties and the causes of poor solubility and poor permeability. Journal of Pharmacological and Toxicological Methods, 44(1), 235–249. https://doi.org/10.1016/S1056-8719(00)00107-6
   PubMed Web of Science ®Google Scholar
• Lipworth, B. J. (2005). Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease. Lancet (London, England), 365(9454), 167–175. https://doi.org/10.1016/S0140-6736(05)17708-3
   PubMed Web of Science ®Google Scholar
• Liu, X., Luo, H.-B., Huang, Y.-Y., Bao, J.-M., Tang, G.-H., Chen, Y.-Y., Wang, J., & Yin, S. (2014). Selaginpulvilins A-D, new phosphodiesterase-4 inhibitors with an unprecedented skeleton from Selaginella pulvinata. Organic Letters, 16(1), 282–285. https://doi.org/10.1021/ol403282f
   PubMed Web of Science ®Google Scholar
• Madhavi Sastry, G., Adzhigirey, M., Day, T., Annabhimoju, R., & Sherman, W. (2013). Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments. Journal of Computer-Aided Molecular Design, 27(3), 221–234. https://doi.org/10.1007/s10822-013-9644-8
   PubMed Web of Science ®Google Scholar
• Malik, V., Kumar, V., Kaul, S. C., Wadhwa, R., & Sundar, D. (2021). Computational Insights into the potential of Withaferin-A, Withanone and caffeic acid phenethyl ester for treatment of Aberrant-EGFR driven lung cancers. Biomolecules, 11(2), 160. https://doi.org/10.3390/biom11020160
   PubMed Web of Science ®Google Scholar
• Massimi, M., Ragusa, F., Cardarelli, S., & Giorgi, M. (2019). Targeting cyclic AMP signalling in hepatocellular carcinoma. Cells, 8(12). https://doi.org/10.3390/cells8121511
   Google Scholar
• Matias, P. M., Donner, P., Coelho, R., Thomaz, M., Peixoto, C., Macedo, S., Otto, N., Joschko, S., Scholz, P., Wegg, A., Bäsler, S., Schäfer, M., Egner, U., & Carrondo, M. A. (2000). Structural evidence for ligand specificity in the binding domain of the human androgen receptor. Implications for pathogenic gene mutations. The Journal of Biological Chemistry, 275(34), 26164–26171. https://doi.org/10.1074/jbc.M004571200
   PubMed Web of Science ®Google Scholar
• Munagala, R., Kausar, H., Munjal, C., & Gupta, R. C. (2011). Withaferin A induces p53-dependent apoptosis by repression of HPV oncogenes and upregulation of tumor suppressor proteins in human cervical cancer cells. Carcinogenesis, 32(11), 1697–1705. https://doi.org/10.1093/carcin/bgr192
   PubMed Web of Science ®Google Scholar
• Orlando, B. J., & Malkowski, M. G. (2016). Substrate-selective inhibition of cyclooxygeanse-2 by fenamic acid derivatives is dependent on peroxide tone. The Journal of Biological Chemistry, 291(29), 15069–15081. https://doi.org/10.1074/jbc.M116.725713
   PubMed Web of Science ®Google Scholar
• Powers, G. L., Hammer, K. D. P., Domenech, M., Frantskevich, K., Malinowski, R. L., Bushman, W., Beebe, D. J., & Marker, P. C. (2015). Phosphodiesterase 4D inhibitors limit prostate cancer growth potential. Molecular Cancer Research: MCR, 13(1), 149–160. https://doi.org/10.1158/1541-7786.MCR-14-0110
   PubMed Web of Science ®Google Scholar
• Raker, V. K., Becker, C., & Steinbrink, K. (2016). The cAMP Pathway as therapeutic target in autoimmune and inflammatory diseases. Frontiers in Immunology, 7, 123. https://doi.org/10.3389/fimmu.2016.00123
   PubMed Web of Science ®Google Scholar
• Ricciarelli, R., & Fedele, E. (2015). Phosphodiesterase 4D: An enzyme to remember. British Journal of Pharmacology, 172(20), 4785–4789. https://doi.org/10.1111/bph.13257
   PubMed Web of Science ®Google Scholar
• Ricciotti, E., & FitzGerald, G. A. (2011). Prostaglandins and inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(5), 986–1000. https://doi.org/10.1161/ATVBAHA.110.207449
   PubMed Web of Science ®Google Scholar
• Richter, W., Menniti, F. S., Zhang, H. T., & Conti, M. (2013). PDE4 as a target for cognition enhancement. Expert Opinion on Therapeutic Targets, 17(9), 1011–1027. https://doi.org/10.1517/14728222.2013.818656
   PubMed Web of Science ®Google Scholar
• Roos, K., Wu, C., Damm, W., Reboul, M., Stevenson, J. M., Lu, C., Dahlgren, M. K., Mondal, S., Chen, W., Wang, L., Abel, R., Friesner, R. A., & Harder, E. D. (2019). OPLS3e: Extending force field coverage for drug-like small molecules. Journal of Chemical Theory and Computation, 15(3), 1863–1874. https://doi.org/10.1021/acs.jctc.8b01026
   PubMed Web of Science ®Google Scholar
• Santhi, N., & Aishwarya, S. (2011). Insights from the molecular docking of withanolide derivatives to the target protein PknG from Mycobacterium tuberculosis. Bioinformation, 7(1), 1–4. https://doi.org/10.6026/97320630007001
   PubMedGoogle Scholar
• Schrödinger. (2020). Protein preparation wizard, Epik, impact, prime, LigPrep, glide. Schrödinger, LLC; Desmond molecular dynamics system. D. E. Shaw Research; Maestro-desmond interoperability tools. Schrödinger (Version 2).
   Google Scholar
• Schudt, C., Winder, S., Muller, B., & Ukena, D. (1991). Zardaverine as a selective inhibitor of phosphodiesterase isozymes. Biochemical Pharmacology, 42(1), 153–162. https://doi.org/10.1016/0006-2952(91)90694-Z
   PubMed Web of Science ®Google Scholar
• Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., & Ideker, T. (2003). Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Research, 13(11), 2498–2504. https://doi.org/10.1101/gr.1239303
   PubMed Web of Science ®Google Scholar
• Shen, M. R., Chiang, P. H., Yang, R. C., Hong, C. Y., & Chen, S. S. (1991). Pentoxifylline stimulates human sperm motility both in vitro and after oral therapy. British Journal of Clinical Pharmacology, 31(6), 711–714. https://doi.org/10.1111/j.1365-2125.1991.tb05600.x
   PubMed Web of Science ®Google Scholar
• Son, H., Lu, Y. F., Zhuo, M., Arancio, O., Kandel, E. R., & Hawkins, R. D. (1998). The specific role of cGMP in hippocampal LTP. Learning & Memory (Cold Spring Harbor, N.Y.), 5(3), 231–245.
   PubMed Web of Science ®Google Scholar
• Steinberg, S. F. (2008). Structural basis of protein kinase C isoform function. Physiological Reviews, 88(4), 1341–1378. https://doi.org/10.1152/physrev.00034.2007
   PubMed Web of Science ®Google Scholar
• Sun, L., Quan, H., Xie, C., Wang, L., Hu, Y., & Lou, L. (2014). Phosphodiesterase 3/4 inhibitor zardaverine exhibits potent and selective antitumor activity against hepatocellular carcinoma both in vitro and in vivo independently of phosphodiesterase inhibition. PLoS One, 9(3), e90627. https://doi.org/10.1371/journal.pone.0090627
   PubMed Web of Science ®Google Scholar
• Wagner, J., von Matt, P., Sedrani, R., Albert, R., Cooke, N., Ehrhardt, C., Geiser, M., Rummel, G., Stark, W., Strauss, A., Cowan-Jacob, S. W., Beerli, C., Weckbecker, G., Evenou, J.-P., Zenke, G., & Cottens, S. (2009). Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes. Journal of Medicinal Chemistry, 52(20), 6193–6196. https://doi.org/10.1021/jm901108b
   PubMed Web of Science ®Google Scholar
• Yeo, C. D., Kim, J. W., Ha, J. H., Kim, S. J., Lee, S. H., Kim, I. K., & Kim, Y. K. (2014). Chemopreventive effect of phosphodieasterase-4 inhibition in benzo(a)pyrene-induced murine lung cancer model. Experimental Lung Research, 40(10), 500–506. https://doi.org/10.3109/01902148.2014.950769
   PubMed Web of Science ®Google Scholar
• Zamarbide, M., Mossa, A., Munoz-Llancao, P., Wilkinson, M. K., Pond, H. L., Oaks, A. W., & Manzini, M. C. (2019). Male-specific cAMP signaling in the hippocampus controls spatial memory deficits in a mouse model of autism and intellectual disability. Biological Psychiatry, 85(9), 760–768. https://doi.org/10.1016/j.biopsych.2018.12.013
   PubMed Web of Science ®Google Scholar
• Zhang, X., Perez-Sanchez, H., & Lightstone, F. C. (2017). A comprehensive docking and MM/GBSA rescoring study of ligand recognition upon binding antithrombin. Current Topics in Medicinal Chemistry, 17(14), 1631–1639. https://doi.org/10.2174/1568026616666161117112604
   PubMed Web of Science ®Google Scholar
• Zhao, P., Chen, S.-K., Cai, Y.-H., Lu, X., Li, Z., Cheng, Y.-K., Zhang, C., Hu, X., He, X., & Luo, H.-B. (2013). The molecular basis for the inhibition of phosphodiesterase-4D by three natural resveratrol analogs. Isolation, molecular docking, molecular dynamics simulations, binding free energy, and bioassay. Biochimica et Biophysica Acta, 1834(10), 2089–2096. https://doi.org/10.1016/j.bbapap.2013.07.004
   PubMed Web of Science ®Google Scholar
• Zhong, J.-S., Huang, Y.-Y., Zhang, T.-H., Liu, Y.-P., Ding, W.-J., Wu, X.-F., Xie, Z.-Y., Luo, H.-B., & Wan, J.-Z. (2015). Natural phosphodiesterase-4 inhibitors from the leaf skin of Aloe barbadensis Miller. Fitoterapia, 100, 68–74. https://doi.org/10.1016/j.fitote.2014.11.018
   PubMed Web of Science ®Google Scholar