High Cell Permeability Does Not Predict Oral Bioavailability for Analogues of Cyclic Heptapeptide Sanguinamide A*
Daniel S. Nielsen A , Rink-Jan Lohman
A , Huy N. Hoang A , David P. Fairlie A B C and Timothy A. Hill A C
A Division of Chemistry and Structural Biology, University of Queensland, Brisbane, Qld 4072, Australia.
B Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Queensland, Brisbane, Qld 4072, Australia.
C Corresponding authors. Email: d.fairlie@imb.uq.edu.au; t.hill@imb.uq.edu.au
Australian Journal of Chemistry 73(4) 344-351 https://doi.org/10.1071/CH19479
Submitted: 27 September 2019 Accepted: 4 December 2019 Published: 25 February 2020
Abstract
The cyclic heptapeptide derivative, sanguinamide A, is a model scaffold for studying how component amino acids, heterocycles, and N-methylation influence membrane permeability and oral bioavailability. Membrane permeable sanguinamide A analogues have been reported, but there is limited data on their pharmacokinetic properties in vivo. Here we report pharmacokinetic properties for highly cell and membrane permeable sanguinamide A analogues in rats and find that there is no correlation between reported permeability in vitro and oral bioavailability in vivo. We show that N-methylation of sanguinamide A analogues gives compounds with greater flexibility, greater susceptibility to degradation by rat liver microsomes, and lower oral bioavailability in rats.
References
[1] D. J. Craik, D. P. Fairlie, S. Liras, D. Price, Chem. Biol. Drug Des. 2013, 81, 136.| Crossref | GoogleScholarGoogle Scholar | 23253135PubMed |
[2] A. Henninot, J. C. Collins, J. M. Nuss, J. Med. Chem. 2018, 61, 1382.
| Crossref | GoogleScholarGoogle Scholar | 28737935PubMed |
[3] D. S. Nielsen, N. E. Shepherd, W. Xu, A. J. Lucke, M. J. Stoermer, D. P. Fairlie, Chem. Rev. 2017, 117, 8094.
| Crossref | GoogleScholarGoogle Scholar | 28541045PubMed |
[4] C. A. Lipinski, F. Lombardo, B. W. Dominy, P. J. Feeney, Adv. Drug Deliv. Rev. 1997, 23, 3.
| Crossref | GoogleScholarGoogle Scholar |
[5] C. A. Lipinski, Drug Discov. Today. Technol. 2004, 1, 337.
| Crossref | GoogleScholarGoogle Scholar | 24981612PubMed |
[6] J. E. Bock, J. Gavenonis, J. A. Kritzer, ACS Chem. Biol. 2013, 8, 488.
| Crossref | GoogleScholarGoogle Scholar | 23170954PubMed |
[7] C. K. Wang, D. J. Craik, Biopolymers 2016, 106, 901.
| Crossref | GoogleScholarGoogle Scholar | 27178381PubMed |
[8] T. R. White, C. M. Renzelman, A. C. Rand, T. Rezai, C. M. McEwen, V. M. Gelev, R. A. Turner, R. G. Linington, S. S. F. Leung, A. S. Kalgutkar, J. N. Bauman, Y. Zhang, S. Liras, D. A. Price, A. M. Mathiowetz, M. P. Jacobson, R. S. Lokey, Nat. Chem. Biol. 2011, 7, 810.
| Crossref | GoogleScholarGoogle Scholar | 21946276PubMed |
[9] C. K. Wang, S. E. Northfield, B. Colless, S. Chaousis, I. Hamernig, R.-J. Lohman, D. S. Nielsen, C. I. Schroeder, S. Liras, D. A. Price, D. P. Fairlie, D. J. Craik, Proc. Natl. Acad. Sci. USA 2014, 111, 17504.
| Crossref | GoogleScholarGoogle Scholar | 25416591PubMed |
[10] C. K. Wang, S. E. Northfield, J. E. Swedberg, B. Colless, S. Chaousis, D. A. Price, S. Liras, D. J. Craik, Eur. J. Med. Chem. 2015, 97, 202.
| Crossref | GoogleScholarGoogle Scholar | 25974856PubMed |
[11] L. Gentilucci, R. De Marco, L. Cerisoli, Curr. Pharm. Des. 2010, 16, 3185.
| Crossref | GoogleScholarGoogle Scholar | 20687878PubMed |
[12] I. R. Kumarasinghe, V. J. Hruby, in Peptide Chemistry and Drug Design (Ed. B. M. Dunn) 2015, pp. 247–270 (John Wiley & Sons, Inc.: Hoboken, NJ).
[13] A. F. B. Räder, F. Reichart, M. Weinmueller, H. Kessler, Bioorg. Med. Chem. 2018, 26, 2766.
| Crossref | GoogleScholarGoogle Scholar |
[14] J. Chatterjee, C. Gilon, A. Hoffman, H. Kessler, Acc. Chem. Res. 2008, 41, 1331.
| Crossref | GoogleScholarGoogle Scholar | 18636716PubMed |
[15] D. S. Dalisay, E. W. Rogers, A. S. Edison, T. F. Molinski, J. Nat. Prod. 2009, 72, 732.
| Crossref | GoogleScholarGoogle Scholar | 19254038PubMed |
[16] D. S. Nielsen, H. N. Hoang, R.-J. Lohman, F. Diness, D. P. Fairlie, Org. Lett. 2012, 14, 5720.
| Crossref | GoogleScholarGoogle Scholar | 23130644PubMed |
[17] D. S. Nielsen, H. N. Hoang, R.-J. Lohman, T. A. Hill, A. J. Lucke, D. J. Craik, D. J. Edmonds, D. A. Griffith, C. J. Rotter, R. B. Ruggeri, D. A. Price, S. Liras, D. P. Fairlie, Angew. Chem. Int. Ed. 2014, 53, 12059.
| Crossref | GoogleScholarGoogle Scholar |
[18] U. Holzgrabe, Chem. Biol. 2015, 22, 981.
| Crossref | GoogleScholarGoogle Scholar | 26295835PubMed |
[19] A. Kling, P. Lukat, D. V. Almeida, A. Bauer, E. Fontaine, S. Sordello, N. Zaburannyi, J. Herrmann, S. C. Wenzel, C. König, N. C. Ammerman, M. Belén Barrio, K. Borchers, F. Bordon-Pallier, M. Brönstrup, G. Courtemanche, M. Gerlitz, M. Geslin, P. Hammann, D. W. Heinz, H. Hoffmann, S. Klieber, M. Kohlmann, M. Kurz, C. Lair, H. Matter, E. Nuermberger, S. Tyagi, L. Fraisse, J. H. Grosset, S. Lagrange, R. Müller, Science 2015, 348, 1106.
| Crossref | GoogleScholarGoogle Scholar | 26045430PubMed |
[20] J. Grevel, E. Nuesch, E. Abisch, K. Kutz, Eur. J. Clin. Pharmacol. 1986, 31, 211.
| Crossref | GoogleScholarGoogle Scholar | 3803418PubMed |
[21] A. T. Bockus, J. A. Schwochert, C. R. Pye, C. E. Townsend, V. Sok, M. A. Bednarek, R. S. Lokey, J. Med. Chem. 2015, 58, 7409.
| Crossref | GoogleScholarGoogle Scholar | 26308180PubMed |
[22] D. A. Smith, K. Beaumont, T. S. Maurer, L. Di, J. Med. Chem. 2019, 62, 2245.
| Crossref | GoogleScholarGoogle Scholar | 30281973PubMed |
[23] L. Di, AAPS J. 2015, 17, 134.
| Crossref | GoogleScholarGoogle Scholar | 25366889PubMed |
[24] J. B. Houston, Biochem. Pharmacol. 1994, 47, 1469.
| Crossref | GoogleScholarGoogle Scholar | 8185657PubMed |
[25] K. Thelen, J. B. Dressman, J. Pharm. Pharmacol. 2009, 61, 541.
| Crossref | GoogleScholarGoogle Scholar | 19405992PubMed |
[26] D. S. Nielsen, R.-J. Lohman, H. N. Hoang, T. A. Hill, A. Jones, A. J. Lucke, D. P. Fairlie, ChemBioChem 2015, 16, 2289.
| Crossref | GoogleScholarGoogle Scholar | 26336864PubMed |
[27] T. Vorherr, I. Lewis, J. Berghausen, S. Desrayaud, M. Schaefer, Int. J. Pept. Res. Ther. 2018, 24, 35.
| Crossref | GoogleScholarGoogle Scholar | 29527142PubMed |
