DESIGN, SYNTHESIS, DOCKING, ANTITUMOR SCREENING, AND ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION PREDICTION OF NEW HESPERDIN DERIVATIVE

  • HANADY S AL-SHMGANI Department of College of Education for Pure Science Ibn Al-Haitham, University of Baghdad, Iraq.
  • RAIED MUSTAFA SHAKIR Department of College of Education for Pure Science Ibn Al-Haitham, University of Baghdad, Iraq.
  • AHMED W NASER Department of College of Science, University of Baghdad, Iraq.
  • OLUSOLA OLALEKAN ELEKOFEHINTI Department of Biochemistry, Bioinformatics and Molecular Biology Unit, Federal University of Technology, Akure, Ondo State, Nigeria.

Abstract

Objective: Hesperidin (HSP) is a pharmacologically active organic compound found in citrus fruits and peppermint. We synthesized a new HSP derivative by reacting it with 5-Amino-1,3,4-thiadiazole-2-thiol in acetic acid.


Methods: This compound was characterized by Fourier-transform infrared, proton nuclear magnetic resonance, and electron impact mass spectra. A molecular docking study explores the predicted binding of the compound and its possible mode of action. Bioavailability, site of absorption, drug mimic, and topological polar surface was predicted using absorption, distribution, metabolism, and excretion (ADME) studies.


Results: The docking study predicts that the new compound binds to the active sites of Aurora-B and the MST3 pocket and has good ADME properties. Moreover, the thiazole ring and the presence of the electron releasing groups and hydrogen bond interaction with amino acid residues within the active sites play an important role in enhancing the antioxidant activity.


Conclusion: In the present study, a new HSP derivative has been synthesized and characterized successfully and a theoretically promising antioxidant and anticytotoxic active agent introduced. We have shown the detailed binding analysis of 1,3,4-thiadiazol and hydrogen bonds with the inhibitor binding cavity of Aurora B and MST3. This could provide the development of some effective compounds against different diseases.

Keywords: Hesperidin derivative, Molecular docking, Absorption, distribution, metabolism, excretion, Aurora B

References

1. Bohm B. Introduction of Flavonoids. 1st ed. Amsterdam: Harwood Academic Publishers; 1998.
2. Seyoum A, Asres K, El-Fiky FK. Structure-radical scavenging activity relationships of flavonoids. Phytochemistry 2006;67:2058-70.
3. Roohbakhsh A, Parhiz H, Soltani F, Rezaee R, Iranshahi M. Neuropharmacological properties and pharmacokinetics of the citrus flavonoids hesperidin and hesperetin-a mini-review. Life Sci 2014;113:1-6.
4. Al-Rikabi RH, Al-Shmgani HS. Evaluation of hesperidin protective effect on lipopolysaccharide-induced inflammation and lipid peroxidation in BALB/C male mice. Res J Pharm Tech 2018;11:5513-6.
5. Das S, Mandal SK. Current developments on anti-inflammatory natural medicines. Asian J Pharm Clin Res 2018;11:61-5.
6. Majumdar S, Srirangam R. Solubility, stability, physicochemical characteristics and in vitro ocular tissue permeability of hesperidin: A natural bioflavonoid. Pharm Res 2009;26:1217-25.
7. Cao R, Xue Y, Strappe P, Blanchard C, Zhou Z. Natural products derived from tea on the solubility of hesperidin by LC-TOF/MS and NMR. Int J Food Properties 2017;20:5270-8.
8. Jakovljevi K, Mati IZ, Stanojkovi T, Krivokua A, Markovi V, Joksovi MD, et al. Synthesis, antioxidant and antiproliferative activities of 1,3,4-thiadiazoles derived from phenolic acids. Bioorg Med Chem Lett 2017;27:3709.
9. Omar YM, Abdu-Allah HH, Abdel-Moty SG. Synthesis, biological evaluation and docking study of 1,3,4-thiadiazole-thiazolidinone hybrids as anti-inflammatory agents with dual inhibition of COX-2 and 15-LOX. J Bioorg Chem 2018;80:461-71.
10. Murali A, Shaji A. Synthesis characterization, and evaluation of antibacterial and antidepressant activities of novel tetrasubstituted imidazole derivatives. Asian J Pharm Clin Res 2019;12:93-7.
11. Gill-Lzquicrdo A, Gil MI, Tomas-Barbcran FA. Influence of industrial processing on arrange juice flavanune solubility and transformation to chalcones under gastrointestinal conditions. J Agric food Chem 2003;51:3024-328.
12. Available from: http://www. Molinspiration.com. 13. Goineau S, Legrand C, Froget G. Whole-cell configuration of the patch-clamp technique in the hERG channel assay to predict the ability of a compound to prolong QT interval. Curr Protoc Pharmacol 2012;10:10-5.
14. Ghafourian T, Amin Z. QSAR models for the prediction of plasma protein binding. Bioimpacts 2013;3:21-7.
15. Hochleitner J, Akram M, Ueberall M, Davis RA, Waltenberger B, Stuppner H, et al. A combinatorial approach for the discovery of cytochrome P450 2D6 inhibitors from nature. J Sci Rep 2017;7:1-13.
16. Keen N, Taylor S. Aurora-kinase inhibitors as anticancer agents. Nat Rev Cancer 2004;4:927-36.
17. Kaitna S, Pasierbek P, Jantsch M, Loidl J, Glotzer M. The Aurora B kinase AIR-2 regulates kinetochores during mitosis and is required for separation of homologous chromosomes during meiosis. Curr Biol 2002;12:798-812. 18. Hauf S, Cole RW, LaTerra S, Zimmer C, Schnapp G, Walter R, et al. The small molecule hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint. J Cell Biol 2003;161:281-94.
19. Harrington EA, Bebbington D, Moore J, Rasmussen RK, Nakayama AO, Ajose-Adeogun T, et al. A potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med 2004;10:262-7.
20. Saiprasad G, Chitra P, Manikandan R, Sudhandiran G. Hesperidin induces apoptosis and triggers autophagic markers through inhibition of Aurora-A mediated phosphoinositide-3-kinase/Akt/mammalian target of rapamycin and glycogen synthase kinase-3 beta signalling cascades in experimental colon carcinogenesis. Eur J Cancer 2014;50:2489-507.
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AL-SHMGANI, H. S., RAIED MUSTAFA SHAKIR, AHMED W NASER, and O. O. ELEKOFEHINTI. “DESIGN, SYNTHESIS, DOCKING, ANTITUMOR SCREENING, AND ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION PREDICTION OF NEW HESPERDIN DERIVATIVE”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 13, no. 1, Oct. 2019, pp. 24-31, doi:10.22159/ajpcr.2020.v13i1.35684.
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