IN SILICO DRUG EVALUATION AND DRUG RESEARCH OF BIOACTIVE MOLECULE METHYL 4-BROMO-2-FLUOROBENZOATE

Öz

Objective: The biochemical analysis plays an important role in pharmaceutical chemistry. Fungal infections are the most common infectious disease worldwide. The result of this research study can be very useful for the pharmacy and drug discovery process.

Material and Method: The experimental UV-Vis absorption is recorded with DMSO as solvent in SAIF IIT (Sophisticated Analytical Instrument Facility, Indian Institute of Technology, Chennai, India). Biologically active sites are reviewed by Gauss software via MEP. Toxic predictions are completed with the Preadme online tool. Protein-Ligand interaction was studied by Autodock tools 4.2.6.

Result and Discussion: Methyl 4-bromo-2-fluorobenzoate (MBF) molecule is structurally stable. Hydrogen binding sites of MBF molecule are found around carbonyl group. The HOMO/LUMO energy values are -6.509 eV and -4.305 eV, respectively. Stabilization energy (3.63 kcal/mol) was calculated as O4=C11 atoms. Toxicity parameters are calculated. Overall results shows stabilized MBF molecule is intoxic and suitable for drug nature of fungal diseases.

Anahtar Kelimeler

• DFT
• drug likeness
• molecular docking
• NBO
• toxicity

BİYOAKTİF MOLEKÜL METİL 4-BROMO-2-FLOROBENZOAT'IN İN SİLİKO İLAÇ DEĞERLENDİRMESİ VE ARAŞTIRMASI

Öz

Amaç: Biyokimyasal analiz farmasötik kimyada önemli bir rol oynar. Mantar enfeksiyonları dünya çapında en yaygın bulaşıcı hastalıktır. Bu araştırma çalışmasının sonucu, eczacılık ve ilaç keşif süreci için çok faydalı olabilir.

Gereç ve Yöntem: Deneysel UV-Vis absorpsiyonu çözücü olarak DMSO kullanılarak SAIF IIT'de (Gelişmiş Analitik Cihaz Tesisi, Hindistan Teknoloji Enstitüsü, Chennai, Hindistan) kaydedildi. Biyolojik olarak aktif bölgeler, Gauss yazılımı tarafından MEP aracılığıyla incelendi. Toksisite tahminlemesi Preadme çevrimiçi aracı ile tamamlandı. Protein-Ligand etkileşimi Autodock 4.2.6 programıyla incelendi.

Sonuç ve Tartışma: Metil 4-bromo-2-florobenzoat (MBF) molekülü yapısal olarak kararlıdır. MBF molekülünün hidrojen bağlanma yerleri karbonil grubu çevresinde bulunur. HOMO/LUMO enerji değerleri, sırasıyla -4,305 eV ve -6.509 eV'dir. Stabilizasyon enerjisi (3.63 kcal/mol) O4 = C11 atomları olarak hesaplandı. Toksisite parametreleri hesaplandı. MBF molekülü ile mantar proteini arasında iki hidrojen bağı oluştu. Genel sonuçlar, stabilize edilmiş MBF molekülünün zehirli olmadığını ve mantar hastalıkları için ilaç olarak uygun olduğunu göstermektedir.

Anahtar Kelimeler

• DFT
• ilaç benzerliği
• moleküler yerleştirme
• NBO
• toksisite

Kaynakça

1. Reference1 Hudlicky, M., Pavalath, A.E., (1995) Chemistry of organic Fluorine Compounds II.A Critical Review, American Chemical Society, Washigton, DC.
2. Reference2 Banks, R. E., Smart, B. E., Tatlow, J. C., (1994), Organoflourine Chemistry: Principalsand Applications, Plenum Press, New York.
3. Reference3 Edwards, P. N., (1994) Uses of Flourine in Chemotherapyin Organoflouine Chemistry:Principles and Applications, Plenum Press, New York.
4. Reference4 Ankersen, M., Peschke, B., Hansen, S. B., Hansen, T. K., (1997) Investigation of bioisosters of the growth hormone secretagogue L-692,429, Bioorg. Med. Chem. Lett. 7, 1293-1298.
5. Reference5 Revesz, L., Blum, E., E. Di Padova, T., Buhl, R., Feifel H., Gram, P., Hiestand, U., Manning, U., Rucklin G., (2004) Novel p38 inhibitors with potent oral efficacy in several models of rheumatoid arthritis, Bioorg. Med. Chem. Lett. 14 3595-3599.
6. Reference6 Lin F. C., Yang S., Chang, J. C., Y., Kuo, C. S., Lee, R. M., Huang, J. L., (2005), Synthesis and anticancer activity of benzyloxybenzaldehyde derivatives against HL-60 cells, Bioorg. Med. Chem. 13, 1537-1544.
7. Reference7 Xuanand, X., Zhai, C., Quantum chemical studies of FT-IR and Raman spectra of methyl 2, 5- dichlorobenzoate, (2011) Spectrochim. Acta A. 79 1663-1668.
8. Reference8 Glendening, P. E. D., Reed, A. E., Carpenter, J. E., Weinhold, F., (1998) NBO Version 3.1, Theoretical Chemistry Institute and Department of Chemistry, University of Wisconsin, Madison.

9. Reference9 Asif, F. B., Khan, F. L. A., Muthu, S., Raja, M., (2021) Computational evaluation on molecular structure ( Monomer , Dimer ), RDG , ELF , electronic ( HOMO-LUMO , MEP ) properties, and spectroscopic profiling of 8-Quinolinesulfonamide with molecular docking studies. Comput. Theor. Chem. 1198, 113169.
10. Reference10 Fathima, R. B., Prasana, J. C., Muthu, Abraham, C. S., (2019) Molecular docking studies, charge transfer excitation and wave function analyses (ESP, ELF, LOL) on valacyclovir: A potential antiviral drug. Comput. Biol. Chem. 78, 9–17.
11. Reference11 Frisch, M.J., Trucks G.W., Schlegel, H.B., Scuseria G.E., Robb M.A., Cheeseman J.R.,Ortiz J.V., Cioslowski J, Fox D.J., (2009) Gaussian 09, Revision A.02,.Gaussian, Inc.,Wallingford CT.
12. Reference12 Viana Nunes, A. M., das Chagas Pereira de Andrade, F., Filgueiras, L. A., de Carvalho Maia, O. A., Cunha, R. L. O. R., Rodezno, S. V. A., Maia Filho, A. L. M., de Amorim Carvalho, F. A., Braz, D. C., & Mendes, A. N. (2020). preADMET analysis and clinical aspects of dogs treated with the Organotellurium compound RF07: A possible control for canine visceral leishmaniasis? Environmental Toxicology and Pharmacology, 80(April 2019). https://doi.org/10.1016/j.etap.2020.103470
13. Reference13 Berman, M. H., J. Westbrook, Z. Feng, Gilliland G., Bhat T. N., Weissig H., Shindyalov I. N., Bourne P. E., (2000), The protein data bank, Nucleic Acids Res. 28 235- 242.
14. Reference14 Morris, G. M., Huey R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., Olson A. J., (2009) AutoDock4 and AutoDockTools 4: Automated docking with selective receptor flexibility, J. Comput. Chem. 16 2785-2791.
15. Reference15 The PyMOL Molecular Graphics System, Version 1. 5.0.4, Schrodinger, LLC, 2009.
16. Reference16 Al-Zaqri, N., Pooventhiran T., Alsalme A., Warad I., John A. M., Thomas R., (2020) Structural and physico-chemical evaluation of melatonin and its solution-state excited properties, with emphasis on its binding with novel coronavirus proteins, J. Mol. Liq. 318 114082. https://doi.org/10.1016/j.molliq.2020.114082.
17. Reference17 Thomas, R., Hossain, M., Mary, Y.S., Resmi, K.S., S. Armaković, S.J. Armaković, A.K. Nanda, V.K. Ranjan, G. Vijayakumar, C. Van Alsenoy, (2018) Spectroscopic analysis and molecular docking of imidazole derivatives and investigation of its reactive properties by DFT and molecular dynamics simulations, J. Mol. Struct. 1158 156–175. https://doi.org/10.1016/j.molstruc.2018.01.021.
18. Reference18 Pandey, M., Muthu, S., Nanje Gowda N. M., (2017) Quantum mechanical and spectroscopic (FT-IR, FT-Raman,1H,13C NMR, UV-Vis) studies, NBO, NLO, HOMO, LUMO and Fukui function analysis of 5-Methoxy-1H-benzo[d]imidazole-2(3H)-thione by DFT studies, J. Mol. Struct. 1130, 511–521. https://doi.org/https://doi.org/10.1016/j.molstruc.2016.10.064.
19. Reference19 Manjusha, P., Prasana J.C., Muthu S., Rizwana B.F., (2019) A computational and spectroscopic interpretation (FT-IR, FT-Raman, UV–vis and NMR) with molecular docking studies on 3-carboxy-2-hydroxy-N, N, N-trimethyl-1-propanaminium hydroxide: A pharmaceutical drug, Chem. Data Collect. 20, 100191. https://doi.org/10.1016/j.cdc.2019.100191.
20. Reference20 Jeeva S., Muthu S., Tamilselvan S., Caroline M.L., Purushothaman P., Sevvanthi S., Vinitha G., Mani G., Growth, spectroscopic studies, and third order non-linear optical analysis of an organic dicarboxylic acid based single crystal: Urea Oxalic acid, Chinese J. Phys. 56 (2018) 1449–1466. https://doi.org/10.1016/j.cjph.2018.05.021.
21. Reference21 Politzer, P., Truhlar D., (2013) Chemical Applications of Atomic and MolecularElectrostatic Potentials: Reactivity, Structure, Scattering, and Energetics of Organic, Inorganic, and Biological Systems, Springer Science Business Media.
22. Reference22 Murray, J.S., Sen K., (1996)Molecular Electrostatic Potentials Conceptsand Applications, Elsevier Science B.V., Amsterdam.
23. Reference23 Shah, U., Patel, S., Patel, M., Gandhi, K., Patel, A., (2020), Identification of chalcone derivatives as putative non-steroidal aromatase inhibitors potentially useful against breast cancer by molecular docking and ADME prediction, Indian J. Chem. -Section B. 59 283–293.
24. Reference24 Psimadas, D., Georgoulias P., Valotassiou, V., Loudos, G., (2012), Molecular Nanomedicine Towards Cancer:, J. Pharm. Sci. 101, 2271–2280. https://doi.org/10.1002/jps.
25. Reference25 Abraham, C.S., Muthu, S., Prasana, J.C., Armaković, S.J., Armaković, S., Rizwana, F. B., B.G. Ben, (2018) Spectroscopic profiling (FT-IR, FT-Raman, NMR and UV-Vis), autoxidation mechanism (H-BDE) and molecular docking investigation of 3-(4-chlorophenyl)-N,N-dimethyl-3-pyridin-2-ylpropan-1-amine by DFT/TD-DFT and molecular dynamics: A potential SSRI drug, Comput. Biol. Chem. 77 131–145. https://doi.org/10.1016/j.compbiolchem.2018.08.010.
26. Reference26 Thomas, R., Mary, Y.S., Resmi, K.S., Narayana, B., Sarojini, B.K., Vijayakumar, G., Van Alsenoy, C., (2020) Two neoteric pyrazole compounds as potential anti-cancer agents : Synthesis , electronic structure , physico-chemical properties and docking analysis, J. Mol. Struct. 1181, 455–466. https://doi.org/10.1016/j.molstruc.2019.01.003.
27. Reference27 Thomas, R., Mary, Y.S., Resmi, K.S., Narayana, B., Sarojini, B.K., Vijayakumar, G., Van Alsenoy, C., (2020) Two neoteric pyrazole compounds as potential anti-cancer agents : Synthesis , electronic structure , physico-chemical properties and docking analysis, J. Mol. Struct. 1181, 455–466. https://doi.org/10.1016/j.molstruc.2019.01.003.
28. Reference28 Pooventhiran, T., Bhattacharyya, U., Rao, D.J., Chandramohan, V., Karunakar, P., Irfan, A., Mary, Y.S., Thomas, R., (2020) Detailed spectra, electronic properties, qualitative non-covalent interaction analysis, solvatochromism, docking and molecular dynamics simulations in different solvent atmosphere of cenobamate, Struct. Chem. 31, 2475–2485. https://doi.org/10.1007/s11224-020-01607-8.
29. Reference29 Thomas, R., Mary, Y.S., Resmi, K.S., Narayana, B., Sarojini, S. B. K., Armaković, S.,. Armaković, S. J, Vijayakumar, G., Van Alsenoy, C., Mohan, B.J., (2019) Synthesis and spectroscopic study of two new pyrazole derivatives with detailed computational evaluation of their reactivity and pharmaceutical potential, J. Mol. Struct. 1181, 599–612. https://doi.org/10.1016/j.molstruc.2019.01.014.
30. Reference30 Thamarai, A., Vadamalar, R., Raja, M., Muthu, S., Narayana, B., Ramesh, P., Sevvanthi, S., Aayisha, S., (2020), Molecular structure conformational analyses, solvent-electronic studies through theoretical studies and biological profiling of (2E)-1-(3-bromo-2-thienyl)-3-(4-chlorophenyl)-prop-2-en-1-one, J. Mol. Struct. 1202 127349. https://doi.org/10.1016/j.molstruc.2019.127349.