Esma Eryilmaz Dogan

In silico binding affinity of multi-therapeutic agent Pinostrobin on various mammalian albumins: Computational evaluation of animal models

Pinostrobin as a famous member of flavonoid family has been investigated in terms of its therapeutic effect on a variety of diseases, and positive effect has been reported in many in vitro and in vivo studies. As one of the essential elements of blood plasma in human body, serum albumin functions a carrier protein for fatty acids, hormones, and drugs because of its abundance and strength in blood. For that, serum albumin plays an important role on the understanding of pharmacological effect of the promising therapeutic agent, pinostrobin. For providing insight into the preclinical studies of albumin targeted therapeutics, we, in this study, investigated the binding characteristics of human serum albumin – pinostrobin complex in terms of binding energy, bounded residues, and association constants, and compared them with various mammalian albumins such as goat, bovine, porcine, rabbit, sheep, and dog albumins. We used molecular modeling and molecular docking methods with the softwares PyRX and PyMol. We found that pinostrobin-human serum albumin had an association constant in between (10.26-20.16)105 M-1 with the interaction energy in a range of (-8.2- (-8.6)) kcal/mol. Among animal proteins, porcine (5IIU) and sheep (4LUF) showing the interaction energy of -8.4 kcal/mol and -8.1 kcal/mol, respectively, were found to be the most appropriate animal models to be used in albumin based preclinical investigations.

PDF

___

1. Isoda H, Motojima H, Onaga S, et al. Analysis of the erythroid differentiation effect of flavonoid apigenin on K562 human chronic leukemia cells. Chem Biol Interact. 2014;220:269-77.
2. Wang Y, Chen S, Yu O, Metabolic engineering of flavonoids in plants and microorganisms. Appl Microbiol Biotechnol. 2011;91:949.
3. Patel NK, Jaiswal G, Bhutani KK. A review on biological sources, chemistry and pharmacological activities of pinostrobin. Nat Prod Res. 2016;30:2017- 7.
4. Gu C, Fu L, Yuan X.. Promoting effect of pinostrobin on the proliferation, differentiation, and mineralization of murine pre-osteoblastic MC3T3-E1 cells. Molecules. 2017;22:1735.
5. Xian YF, Ip SP, Lin ZX, et al. Protective effects of pinostrobin on β-amyloidinduced neurotoxicity in PC12 cells. Cell Mol Neurobiol. 2012;32:1223-30.
6. Mata R, Rojas A, Acevedo L, et al. Smooth muscle relaxing flavonoids and terpenoids from Conyza filaginoides. Planta Med. 1997;63:31-5.
7. Raffa V, Rojas A, Acevedo L, et al. BNNT-mediated irreversible electroporation: its potential on cancer cells. Technol Cancer Res Treat. 2012;11:459-65.
8. Le Bail JC, Aubourg L Habrioux G, Effects of pinostrobin on estrogen metabolism and estrogen receptor transactivation. Cancer Lett. 2000;156:37-44.
9. Charoensin S, Punvittayagul C, Pompimon W, et al. Toxicological and clastogenic evaluation of pinocembrin and pinostrobin isolated from Boesenbergia pandurata in Wistar rats. Thai J Toxicology. 2010;25:29-29.
10. Sleep D, Cameron J, Evans LR. Albumin as a versatile platform for drug half-life extension. Biochim Biophys Acta. 2013;1830:5526-34.
11. Kratz F. Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J Control Release. 2008;132:171-83.
12. Kratz F, Beyer U, Serum proteins as drug carriers of anticancer agents: a review. Drug Deliv. 1998;5:281-99.
13. Schrodinger L, The PyMOL molecular graphics system, version 1.8. Schrodinger LLC, New York, NY, 2015.
14. Dallakyan S, AJ Olson, Small-molecule library screening by docking with PyRx. Methods Mol Biol. 2015;1263:243-50.
15. Morris G, Goodsell D, Pique M, et al. AutoDock Version 4.2: Automated docking of flexible ligands to flexible receptors. Molecular Graphics Lab, The Scripps Research Institute, La Jolla, California, 2009.
16. Eryilmaz E. Multi-targeted anti-leukemic drug design with the incorporation of silicon into Nelarabine: How silicon increases bioactivity. Eur J Pharm Sci. 2019;134:266-73 . 17. Lipinski CA. Avoiding investment in doomed drugs. Curr Drug Discov. 2001;1:17-9.
18. Dogan EE. Computational bioactivity analysis and bioisosteric investigation of the approved breast cancer drugs proposed new design drug compounds: increased bioactivity coming with silicon and boron. Lett Drug Design Discov. 2021;18:1-11.
19. Dogan EE. Computational binding analysis and toxicity evaluation of estrogen receptor with estradiol and the approved SERMs raloxifene, tamoxifen, and toremifene. Med. 2021;10:157-61.
20. FeRoz SR, Sumi RA, Malek SN, et al. A comparative analysis on the binding characteristics of various mammalian albumins towards a multitherapeutic agent, pinostrobin. Exp Anim. 2014;14:0053.
21. Feroz SR, Mohamad SB, Bakri ZS, et al. Probing the interaction of a therapeutic flavonoid, pinostrobin with human serum albumin: multiple spectroscopic and molecular modeling investigations. PloS one. 2013;8:e76067.
22. Krych, J. and L. Gebicka, Catalase is inhibited by flavonoids. IInt J Biol Macromol. 2013;58:148-53.
23. Ragab F, Yahya T, El-Naa M, et al. Design, synthesis and structure–activity relationship of novel semi-synthetic flavonoids as antiproliferative agents. Eur J Med Chem. 2014;82:506-20.