Yoğunluk Fonksiyonel Teorisi Yaklaşımı Kullanılarak Antelmintik Bir İlaç Olan Mebendazol Nitrat Tuzu İçin Yapı-Özellik İlişkisinin Analizi

Year 2022, Volume: 25 Issue: 3, 1055 - 1067, 01.10.2022

Akansha Tyagi Anuj Kumar

https://doi.org/10.2339/politeknik.828211

Cited By: 1

Abstract

Mebendazole, (5-benzoil-1H-benzimidazol-2-il) -karbamik asit metil ester) (MBZ) 'nin çeşitli çoklu bileşenleri, WHO tarafından sentetik bir antelmintik ilaç olarak kabul edilmektedir. Bu çok bileşenli moleküller, özelliklerinde, özellikle çözünürlüklerinde ve solucan enfeksiyonlarını kontrol etmedeki etkinliklerinde farklılıklar gösterir. Bu farklılıklar, bu çoklu bileşenlerin farklı yapılarına atanabilir. Teorik araştırmalar kullanılarak yapı özelliği ilişkisinin anlaşılması, bize MBZ'nin yeni çoklu bileşenini sentezlemek ve özelliklerini tahmin etmek için bir yol sağlayabilir. Bu nedenle, burada, Yoğunluk fonksiyonel teorisi (DFT) yaklaşımını kullanarak yeni bir MBZ çok bileşenli Aktif Farmasötik Bileşen (API) Mebendazol nitrat tuzu (MBZ-N) üzerine elektronik ve spektroskopik araştırmaları rapor ediyoruz. Becke'nin üç parametreli hibrit işlevsel (B3LYP) yöntemi, doğruluk ve hesaplama maliyeti arasında en iyi uzlaşmayı sağlayan 6-311 ++ G (d, p) temel setine sahip tüm hesaplamalar için kullanılmıştır. doğal bağ analizi (NBO), HOMO-LUMO ve Moleküler Elektrostatik Potansiyel (MEP) gibi titreşim spektrumları ve moleküler reaktivite özellikleri analizi. Protein inhibe etme gibi bilojik aktivitesini anlamak için, MBZ-N molekülünün Tirozin-protein kinaz ABL ile moleküler kenetlenme çalışması da rapor edilmiştir.

Keywords

Mebendazole, DFT, titreşim spektrumları, NBO

Analysis of Structure-Property Relationship for an Anthelmintic Drug, Mebendazole Nitrate Salt, using Density Functional Theory Approach

Abstract

Various multicomponent of Mebendazole , (5-benzoyl-1H-benzimidazole- 2-yl)-carbamic acid methyl ester) (MBZ), are recognised by WHO as a synthetic anthelmintic drug. These multicomponent molecules show differences in their properties, mainly in their solubility and efficacy in controlling worm infections. These differences may be assigned to different structure of these multicomponents. Understanding of structure property relationship using theoretical investigations may provide us a way to synthesise new multicomponent of MBZ and estimating their properties. Therefore, here we report electronic and spectroscopic investigations on a new MBZ multicomponent Active Pharmaceutical Ingredient (API) Mebendazole nitrate salt (MBZ-N) using Density functional theory (DFT) approach. Becke’s three- parameter hybrid functional (B3LYP) method has been used for all computations with 6-311++G(d,p) basis set, which gives the best compromise between accuracy and computational cost.Optimized geometry was further used for the calculation of vibrational spectra and molecular reactivity properties analysis such as natural bond analysis (NBO), HOMO-LUMO, and Molecular Electrostatic Potential (MEP). To understand its bilogical activity such as protein inhibiting, the molecular docking study of the MBZ-N molecule with Tyrosine-protein kinase ABL is also reported. 

Keywords

Mebendazole,, DFT, NBO, vibrational spectra

References

• [1] FerreiraF.F., Antonio GutierrezS., Pires RosaP.C., Paiva-SantosC. de O., Crystal structure determination of mebendazole form a using high-resolution synchrotron x-ray powder diffraction data, Int. J. Drug Dev. Res., 3: 26-33,(2011).
• [2] World Health Organization, WHO 19th Model List of Essential Medicines (April 2015) (Amended November 2015), (2015).
• [3] HimmelreichM., RawsonB. J., WatsonT. R., Polymorphic forms of mebendazole, Aust. J. Pharm. Sci., 6 (4): 123-125,(1977).
• [4] SwanepoelE., LiebenbergW., DevarakondaB., De VilliersM.M., Developing a discriminating dissolution test for three mebendazole polymorphs based on solubility differences, Pharmazie, 58:117-12, (2003).
• [5] De VilliersM.M., TerblancheR.J., LiebenbergW., SwanepoelE., DekkerT.G., SongM.,Variable-temperature X-ray powder diffraction analysis of the crystal transformation of the pharmaceutically preferred polymorph C of mebendazole, J. Pharm. Biomed. Anal, 38: 435-441,(2005).
• [6] BlatonN.M., PeetersO.M., DeranterC., (5-Benzoyl- 1H-benzimidazol-2-yl)-carbamic acid methyl ester hydrobromide (mebendazole$HBr), C16H14BrN3O3, Cryst. Struct. Commun., 9 (1): 181-186, (1980).
• [7] BrusauE.V., CamíG.E., NardaG.E., CuffiniS., AyalaA.P., J. Ellena, Synthesis and characterization of a new mebendazole salt: mebendazole hydrochloride, J. Pharm. Sci., 97: 542-552,(2008).
• [8] ChenJ., LuT., New crystalline forms of mebendazole with n-alkyl carboxylic acids: neutral and ionic status, Chin. J. Chem., 31: 635-640,(2013).
• [9] Guti_errez E. L., SouzaM.S., Diniz L. F., Ellena J., Synthesis, characterization and solubility of a new anthelmintic salt: Mebendazole nitrate, Journal of Molecular Structure, 1161: 113-121,(2018).
• [10] Frisch M. J. and Trucks G. W.et. al. GAUSSIAN 09, Revision, Gaussian, Inc., Wallingford, CT, (2010).
• [11] Martin J.M.L.and AlsenoyC. V., Gar2ped, University of Antwerp, (1995).
• [12] PulayP., FogarasiG., Pang F.and BoggsJ.E., Systematic ab initio gradient calculation of molecular geometries, force constants, and dipole moment derivatives, J. Am. Chem. Soc., 101(10): 2550-2560,(1979).
• [13] TrottO., OlsonA. J., Auto Dock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, Journal Of Computational Chemistry, 31(2):455-46,(2010).
• [14] ClarkR. J. H., and HesterR. E., Biomedical Applications of Spectroscopy, Wiley, Chichester, UK, (1996).
• [15] LiR., DhankharD., ChenJ., KrishnamoorthiA., CesarioT.C., RentzepisP. M., Identification of Live and Dead Bacteria: A Raman Spectroscopic Study, in IEEE Access, 7:23549-23559,(2019).
• [16] LiZ., XiaL., LiG. et al., Raman spectroscopic imaging of pH values in cancerous tissue by using polyaniline@gold nanoparticles. Microchim Acta, 186: 162(2019).
• [17] HuF., ShiL., MinW., Biological imaging of chemical bonds by stimulated Raman scattering microscopy. Nat Methods, 16: 830–842,(2019).
• [18] Lazaro-Pacheco D.,Shaaban A.M.,Rehman S., Rehman I., Raman spectroscopy of breast cancer, Journal Applied Spectroscopy Reviews,55(6): 439-475,(2020).
• [19] Maurya A., Rastogi S., Rouillé G.,Huisken F., and Henning T., Astrophysical Journal, 755:120(2012).
• [20] Szafran M., Komasa A., AdamskaE.B., J. Mol. Struct. (Theochem.) 827: 101-107, (2007).
• [21] Pathak S., Kumar A., Tandon P., Molecular structure and vibrational spectroscopic investigation of 4-chloro-4’dimethylamino-benzylidene aniline using density functional theory, 981: 1-9,(2010).
• [22] MorrisG. M.,Huey R., LindstromW., SannerM. F., BelewR. K., GoodsellD.S., and OlsonA.J., Autodock4 and AutoDockTools4: automated docking with selective receptor flexiblity. J. Computational Chemistry, 16: 2785-91,(2009).