Computational Study on Pazopanib and Pemetrexed Anticancer Drug Molecules Interacting with a Small Peptide Link

Year 2021, Volume: 2 Issue: 1, 6 - 9, 29.06.2021

Merve Güreşci Güliz Ak Habibe Yılmaz Şenay Şanlıer Armağan Kınal

https://doi.org/10.51539/biotech.734817

Cited By: 1

Abstract

Cancer is a group of diseases that are defined as uncontrolled cell proliferation, impaired function of vital tissues and cell death. Chemotherapy is treatment using anti-cancer drugs to destroy cancer cells or control the growth of these cells. In chemotherapy applications pharmacologically active anticancer drugs reach with low specificity to tumor tissue, and also their toxicity is dose-dependent. Classical drug administration routes are either oral or intravenous. Orally taken pills result in irregular pharmacokinetics due to the passages of different metabolic pathways and their low specificity. This leads to frequent damage to healthy tissues. Nanoparticle containing drug delivery systems may overcome these harmful side effects partially (or sometimes totally). Binding peptide-drug conjugates inside of some appropriate nanoparticles is one of the prominent methods among targeted drug delivery systems. Such a system containing Pazopanib (Pz) and Pemetrexed (Pm) drug complexes attached to magnetite nanoparticles with a short polypeptide chain (Ala-Lys-Ala-Leu-Arg-Cys) were designed in our laboratory. In the present study, we computationally investigate the conjugation mechanisms of Pz and Pm drug molecules to the above-mentioned polypeptide chain. The stable structures on the complex formation pathways and their free energy values were obtained at the B3LYP/6-31G(d) level in the water. The mechanism of Pept-Pz complex formation has two steps whose free energy barriers are found to be 21.37 and 27.72 kcal/mol. On the other hand, the free energy barrier of the Pept-Pm complex having a single-step mechanism was calculated as 28.16 kcal/mol.

Keywords

Anticancer drugs, Pemetrexed, Pazopanib, DFT-B3LYP

Supporting Institution

TUBITAK

Project Number

213M672

Thanks

We would like to thank for financial support received from The Scientific and Technological Research Council of Turkey (Project ID: 213M672). The numerical calculations reported in this paper were fully performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources).

References

• Auyang YS (2006) Cancer Causes and Cancer Research on Many Levels of Complexity, Available at: http://www.creatingtechnology.org/biomed/cancer Accessed 20 Apr 2015
• Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, et al. (2009) Gaussian 09, Revision D.01.Wallingford CT:Gaussian, Inc.
• Goel HC, Kumar B, Yadav PR, Moshahid M, Rizvi A (2009) Recent Developments in Cancer Therapy by Use of Nanotechnology, Digest J Nanomater Biostr., 4 (1), 1 – 12.
• Hehre WJ, Radom L, Schleyer PVR, Pople JA (1986) Ab Initio Molecular Orbital Theory, John Wiley & Sons, Inc., USA, 11-88.
• Lin CY, Javadi M, Belnap DM, Barrow JR, Pitt WG (2014) Ultrasound sensitive Liposomes containing doxorubicin for drug targeting therapy, Nanomedicine: Nanotechnology, Biology, and Medicine, 10(1), 67–76.
• Liu HL, Wu JH, Min JH, Kim YK (2008) Synthesis of monosized magnetic-optical AuFe alloy nanoparticles. Journal of Applied Physics Part, 103(7), 1-3.
• Miklán Z, Orbán E, Bánóczi Z, Hudecz F (2011) New pemetrexed-peptide conjugates: synthesis, characterization and in vitro cytostatic effect on non-small cell lung carcinoma (NCI-H358) and human leukemia (HL-60) cells, J Pept Sci., 17(12), 805-811.
• Nayak KA, Pal D (2010) Nanotechnology for Targeted Delivery in Cancer Therapeutics, Seeman-ta Institute of Pharmaceutical Sciences, Vol : 1 , Issue : 1.
• Nehru MR, Singh PO (2008) Nanotechnology and Cancer Treatment, Asian J. Exp. Sci., 22-2 , 45-50.
• Soloviev M (2007) Nanobiotechnology today: focus on nanoparticles, Journal of Nanobiotechnology, 5(11), 1-3.
• Tomasi, J, Mennucci B, Cances E (1999) The IEF version of the PCM solvation method: an overview of a new method addressed to study molecular solutes at the QM Ab initio level, J. Mol. Struct, Theochem, 464- 211–226.
• Tuncer M (2008) Globalleşen Kanser Ve Türkiye, Available at: www.nukte.org Accessed 15 Mar 2015
• Vasir JK, Labhasetwar V (2005) Targeted drug delivery in cancer therapy, Technology in Cancer Research and Treatment, 4(4), 363-374.
• Zhang L, Gu FX, Chan JM, Wang AZ, Langer RS, Farokhzad OC (2008) Nanoparticles in Medicine:Therapeutic Applications and Developments, Clinical Pharmacology and Therapeutics, 83, 761-769.
• Widder KJ, Senyei AE (1984) ‘Magnetic albumin microspheres in drug delivery’ Microsheres and Drug Therapy, Eda.: S.S. Davis, L.Illum, J.G.McVie, E. Tomlinson, Elsevier, Amsterdam, 393-411.