[3-(3-bromofenil)-cis-4,5-dihidroisoksazol-4,5-il]bis(metilen)diasetat molekülünün TDOS/PDOS/OPDOS, azaltılmış yoğunluk gradyanı (RDG) ve moleküler yerleştirme çalışmaları

Yıl 2022, , 100 - 110, 05.01.2022

Yeşim Saniye Kara , Aslı Eşme , Seda Sagdinc

https://doi.org/10.25092/baunfbed.870307

Cited By: 4

Öz

Geniş biyolojik aktivite yelpazesi nedeniyle, 4,5-dihidroisoksazol bileşikleri, bir oksijen atomu ve bir nitrojen atomunu bitişik pozisyonda ihtiva eden beş üyeli heterosikliklerin önemli bir ailesini oluşturur. Bu nedenle 4,5-dihidroizoksazol türevi olan [3- (3-bromofenil) -cis-4,5-dihidroisoksazol-4,5-yl] bis (metilen) diasetat [BDBD] bileşiği bu çalışmada incelenmiştir. [BDBD] bileşiğinin fonksiyonel gruplarının kısmi durum yoğunluğu (PDOS), örtüşen nüfus yoğunluğu (OPDOS) ve toplam durum yoğunluğu (TDOS) DFT / B3LYP / 6-311G (d,p) yöntemi kullanılarak teorik olarak değerlendirildi. Azaltılmış yoğunluk gradyanı (RDG), molekülün zayıf etkileşimi, güçlü çekiciliği ve güçlü itme etkileşimlerini incelemek için verildi. PASS (Biyolojik Aktivite Spektrumunu Tahmin etme) analizi aktif olma olasılık verisi 0.273 ile incelenen molekül için kanserojen aktivitesini önerir. [BDBD] bileşiğinin seçilmiş bazı HIV-1 proteaz (1HSG), GyrB ATPase (3U2D) ve VEGFR-2 kinaz enzimi (4AG8) proteinlerine karşı antibakteriyel ve anti-inflamatuar aktiviteleri moleküler yerleştirme yöntemiyle araştırıldı. 1HSG, 3U2D, and 4AG8 hedef proteinleri ile [BDBD] ligandı bağlanma enerjileri sırasıyla -6.11, -4.54, and -4.80 kcal/mol olarak hesaplandı. Sonuçlar literatürle karşılaştırılarak yorumlanmıştır.

Anahtar Kelimeler

DTF, 4,5-dihidroisoksazol, moleküler orbital durum yoğunluğu, azaltılmış yoğunluk gradyanı (RDG), moleküler yerleştirme

TDOS/PDOS/OPDOS, reduced density gradient (RDG) and molecular docking studies of [3-(3-bromophenyl)-cis-4,5-dihydroisoxazole-4,5-diyl]bis(methylene) diacetate

Öz

Due to the wide range of biological activity, 4,5-dihydroisoxazole compounds form an important family of five-membered heterocycles containing an oxygen atom and a nitrogen atom in the adjacent position. Therefore, [3- (3-bromophenyl) -cis-4,5-dihydroisoxazol-4,5-yl] bis (methylene) diacetate [BDBD] compound, which is a derivative of 4,5-dihydroisoxazole, was investigated in this study. The partial density of state (PDOS), the overlap population density of state (OPDOS) and total density of state (TDOS) of functional groups of the [BDBD] compound were theoretically evaluated using the DFT / B3LYP / 6-311G (d, p) method. Reduced density gradient (RDG) was also given to study the weak interaction, strong attraction, and strong repulsion interactions of the studied molecule. The PASS (Prediction of Activity Spectra) analysis predicts the carcinogenic activities with probability to be active value of 0.273 for the studied molecule. The antibacterial and anti-inflammatory activities of the [BDBD] compound against various the HIV-1 protease (1HSG), GyrB ATPase (3U2D), and VEGFR-2 kinase enzyme (4AG8) proteins were studied using molecular docking. The binding energies of 1HSG, 3U2D, and 4AG8 target proteins with [BDBD] ligand were calculated to be -6.11, -4.54, and -4.80 kcal/mol, respectively. Results were interpreted by comparing with the literature.

Anahtar Kelimeler

DFT, 4,5-dihydroisoxazole, molecular orbital density of states, reduced density gradient (RDG), molecular docking

Kaynakça

• Kwiatkowski, S., A new, efficient approach to α, β-unsaturated ketones and β-hydroxy ketones from 4,5-dihydroisoxazoles, Journal of the Chemical Society, Chemical Communications, 19, 1496-1498, (1987).
• Annunziata, R.R., Cinquini, M., Cozzi, F., Gilardi, A., Restelli, A., Enantiomerically pure sulphinyl-4,5-dihydroisoxazoles. Part 1. Stereocontrolled synthesis of optically active β-ketols and γ-amino alcohols, Journal of the Chemical Society, Perkin Transactions 1, 1, 2289-2292, (1985).
• Lee, S.Y., Lee, B.S., Lee, C.W., Oh, D.Y, Synthesis of 4-oxo-2-alkenylphosphonates via nitrile oxide cycloaddition: γ-Acylation of allylic phosphonates, The Journal of Organic Chemistry, 65, 256-257, (2000).
• Yashiro, A., Nishida, Y., Kobayashi, K., Ohno, M., β-Hydroxy Nitrile and β-Hydroxy Oxime Derivatives of [60] Fullerene by Nucleophilic Ring Cleavage of Fulleroisoxazoline and -Isoxazolidine in the Presence of Methanol, Synlett, 3, 361-362, (2000).
• Cwik, A., Hell, Z., Fuchs, A., Halmai, D., Solid Base Catalyzed Synthesis of 5-Substituted 4,5-Dihydroisoxazoles, Tetrahedron Letters, 46, 6563-6566, (2005).
• Karthikeyan, K, Veenus, S.T, Lalitha, K.G., Perumal, P.T., Synthesis and antinociceptive activity of pyrazolyl isoxazolines and pyrazolyl isoxazoles, Bioorganic&Medicanal Chemistry Letters, 19:3370–3373, (2009).
• Rajanarendar, E., Rama, K.S., Nagaraju, D., Govardhan R.K., Kishore B., Reddy Y.N., Environmentally benign synthesis, molecular properties prediction and anti-inflammatory activity of novel isoxazolo[5,4-d] isoxazol-3-yl-aryl-methanones via vinylogous Henry nitroaldol adducts as synthons, Bioorganic&Medicanal Chemistry Letters, 25, 1630–1634, (2015).
• Basha, S.S., Divya, K., Padmaja, A., Padmavathi, V., Synthesis and antimicrobial activity of thiazolyl pyrazoles and isoxazoles. Research on Chemical Intermediates, 41, 10067–10083, (2015).
• Neetu, A., Pradeep, M., The synthetic and therapeutic expedition of isoxazole and its analogs, Medicinal Chemistry Research, 27, 1309–1344, (2018).
• Amir, M., Javed, S.A., Kumar H., Design and synthesis of 3-[3- (substituted phenyl)-4-piperidin-1-ylmethyl/-4-morpholin-4- ylmethyl-4,5-dihydro-isoxazol-5-yl]-1H-indoles as potent antiinflammatory agents, Medicinal Chemistry Research, 19, 299–310, (2010).
• Gautam, K.C., Singh, D.P., Synthesis and antimicrobial activity of some isoxazole derivatives of thiophene, Chemical Science Transactions, 2, 992–996, (2013).
• Martins, M.A.P., Pereira, C.M.P., Zimmermann, N.E.K., Cunico, W., Mouro, S., Beck, P., Zanatta, N., Bonacorso, H.G., Regiospecific synthesis of polyfluorinated heterocycles, Journal of Fluorine Chemistry, 123, 261-265, (2003).
• Kara, Y.S., Substituent effect study on experimental ¹³C NMR chemical shifts of (3-(substituted phenyl)-cis-4,5-dihydroisoxazole-4,5-diyl)bis(methylene) diacetate derivatives, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 151, 723-730, (2015).
• Kara, Y.S., Kara, Y.S., Esme, A., Sagdinc, S.G., Crystal structure, spectral and DFT studies of [3-(3-bromophenyl)-cis-4,5-dihydroisoxazole-4,5-diyl] bis(methylene) diacetate, Journal of Applied Spectroscopy, 88, 3, 501-1-501-12, (2021).
• Frisch, M.J., M.J., Trucks, G.W., Schlegal, H.B., Scuseria, G.E., Robb, M.A., Cheesman, J.R., Zakrzewski, V.G., Mortgomerg Jr. J.A., Stratmann, R.E., Burant, J.C., J., Ortiz, J.V., Baboul, A.G., Stetanov, B.B., Liu, G., Liashenko, A., Piskorz, P., Komaromi, J., Gomperts, R., Martin, R.L., Fox, D.J., Keith, T., M., Replogle E.S. and J.A. Pople, Gaussian 09, Revision A.1, Gaussian Inc., Wallingford CT, (2009).
• Keith,T., Keith T. and Millam J., GaussView, Version 5.0.9, Semichem. Inc., Shawnee Mission KS, (2009).
• Bekce, A.D., Density‐functional thermochemistry. III. The role of exact Exchange, The Journal of Chemical Physics, 98, 5648-5652, (1993).
• Lee, C., Yang, W., Parr, R.G., Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density, Physical Review B, 37, 7, 85-789, (1988).
• Lu, T., Chen, F., Multiwfn: A multifunctional wavefunction analyzer, Journal of Computational Chemistry, 33, 580-592, (2012).
• Humphrey, W., Dalke, A., Schulten, K., VMD: Visual molecular Dynamics, Journal of Molecular Graphics, 14, 33-38, (1996).
• Johnson, E.R., Keinan, S., Morisanchez, P., Contrerasgarcia, J., Cohen, A.J., Yang, W., Revealing Noncovalent Interactions, Journal of the American Chemical Society, 132, 6498-6506, (2010).
• Lagunin, A., Stepanchikova, A., Filimonov, D., Poroikov, V., PASS: prediction of activity spectra for biologically active substances, Bioinformatics, 16, 747-748, (2000).
• Panda, S.S., Chowdary, P.V.R., Jayashree, B.S., Synthesis, Antiinflammatory and Antibacterial Activity of Novel Indolyl-isoxazoles, Indian Journal of Pharmaceutical Science, 71, 684-687, (2009).
• Sanner, M. F., Python: A programming language for software integration and development, Journal of Molecular Grafhics and Modelling, 17, 57-61, (1999).
• Huey, R., Morris, G.M., Olson, A.J., Goodsell, D.S., Software News and Update A Semiempirical Free Energy Force Field with Charge-Based Desolvation, Journal of Computational Chemistry, 28, 1145-1152, (2007).
• Morris, G.M., Goodsell, D.S., Halliday, R.S., Huey, R., Hart, W.E., Belew, R.K., Olson, A.J., Automated Docking Using a Lamarckian Genetic Algorithm and and Empirical Binding Free Energy Function, Journal of Computational Chemistry, 19, 1639-1661, (1998).
• Kamalneet, K., Vinod, K., Anil, K.S., Girish K.G., Isoxazoline containing natural products as anticancer agents: A review, European Journal of Medicinal Chemistry, 77, 121-133, (2014).
• Maryam, A. J., Oluwakemi E., Nkululeko D., Michael S., Virtual screening, molecular docking studies and DFT calculations of FDA approved compounds similar to the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz, Heliyon, 6, e04642, (2020).