A Novel Anthraquinone-Based Azo Compound: Synthesis, Quantum Chemical Calculations and Investigation of ADMET Properties

Yıl 2023, , 660 - 672, 28.09.2023

Mehmet Ulutürk , Çiğdem Karabacak Atay , Bülent Dede , Tahir Tilki

https://doi.org/10.17798/bitlisfen.1279496

Öz

This study involved the synthesis of the potentially drug candidate 2-((9,10-dioxo-9,10-dihydroanthracen-2-yl)diazenyl)-5-hydroxybenzoic acid (DHA), the elucidation of its structure using spectroscopic techniques and the determination of the compound's lowest energy structure using the DFT/B3LYP method and the 6-311G(d,p) basis set. The compound's vibration frequencies and NMR chemical shift values were then determined using optimized geometry. The three-dimensional molecular electrostatic potential (MEP) map of the compound and the HOMOs-LUMOs and molecular orbital energies were examined using the DFT approach. The compound's ADMET properties were then determined, and its potential for usage as a drug was assessed. Additionally, the predicted toxicity class and LD50 value for the DHA were established. The outcomes demonstrated that by having ADMET properties, this newly synthesized compound has the potential to be a drug.

Anahtar Kelimeler

Azo, Anthraquinone, DFT, ADMET, Toxicity

Kaynakça

• [1] Y. Liu, M. S. T. Mapa and R. L. Sprando, “Anthraquinones inhibit cytochromes P450 enzyme activi-ty in silico and in vitro,” J. Appl. Toxicol., vol. 41(9), pp.1438-1445, 2021.
• [2] H. Küçükbay, F. M. Parladı, F. Z. Küçükbay, A. Angeli, G. Bartolucci and C.T. Supuran, “Synthesis, antioxidant and carbonic anhydrase inhibitory properties of monopeptide-anthraquinone conju-gates,” Org. Commun., vol. 14, no.3, pp. 255-269, 2021.
• [3] U. Parladı, Ü. Yılmaz, S. A. A. Noma, B. Ateş and H. Küçükbay, “Synthesis of new anthraquinone compounds and evaluation of their considerable xanthine oxidase inhibitory activities,” ARKIVOC, vol. 2022, pp. 158-167, 2022.
• [4] L. Dufossé, “Anthraquinones, the Dr Jekyll and Mr Hyde of the food pigment family,” Food Res. Int., vol. 65, Part B, pp. 132-136, November 2014.
• [5] J. Duval, V. Pecher, M. Poujol and E. Lesellier, “Research advances for the extraction, analysis and uses of anthraquinones: A review,” Indust. Crops and Products, vol. 94, pp. 812–833, 2016.
• [6] S. C. Chien, Y. C. Wu, Z. W. Chen and W. C. Yang, “Naturally occurring anthraquinones: chemis-try and therapeutic potential in autoimmune diabetes,” Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine, pp. 1-13, March 2015.
• [7] F. Zhao, S. Zhao, J. T. Han, Y. F. Wang, Y. N. Wang and C. H. Wang, “Antiviral anthraquinones from the roots of Knoxia valerianoides,” Phytochem. Lett., vol. 11, pp. 57-60, March 2015.
• [8] J. Singh, Y. Hussain, S. Luqman and A. Meena, “Purpurin: A natural anthraquinone with multifac-eted pharmacological activities,” Phytother. Res., vol. 35, no. 5, pp. 2418-2428, 2021.
• [9] A. Ntemafacka, R. V. Singh, S. Ali, J. R. Kuiate and Q. P. Hassan, “Antiviral potential of anthra-quinones from Polygonaceae, Rubiaceae and Asphodelaceae: Potent candidates in the treatment of SARS-COVID-19, A comprehensive review,” South African Journal of Botany, vol. 151, Part A, pp. 146-155, December 2022.
• [10] A. Daina, O. Michielin and V. Zoete, “iLOGP: A simple, robust and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach,” J. Chem. Inform. and Model., vol. 54, no. 12, pp. 3284-3301, 2014.
• [11] A. Daina, O. Michielin and V. Zoete, “SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules,” Sci. Rep., vol. 7, pp. 1-13, 2017.
• [12] M. Gökalp, B. Dede, Ç. Karabacak Atay and T. Tilki, “Triazole based azo molecules as potential antibacterial agents: Synthesis, characterization, DFT, ADME and molecular docking studies,” J. Mol. Struct., vol. 1212, pp. 128140, 2020.
• [13] B. Sezgin, B. Dede, Ç, Karabacak Atay and T. Tilki, “Synthesis, Characterization and Theoretical Calculations of a Novel Azo Derivative with In Vitro and In Silico Biological Studies,” Arab. J. Sci. Eng., vol. 46, pp. 5567–5581, 2021.
• [14] R. Sharma, R.K. Rawal, T.Gaba, N. Singla, M. Malhotra, S. Matharoo and T. R. Bhardwaj, “Design, synthesis and ex vivo evaluation of colon-specific azo based prodrugs of anticancer agents,” Bioor-ganic Med. Chem. Lett., vol. 23, pp. 5332-5338, 2013.
• [15] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, et. al, “Gaussian 09, Revision E.01,” Gaussian Inc Wallingford CT, 2016.
• [16] R. Dennington, T. A. Keith, J. M. Millam, “GaussView, Revision 5.0.9,” Semichem. Inc Shawnee Mission, KS, 2009.
• [17] A. D. Becke, “Density-functional exchange-energy approximation with correct asymptotic behav-ior,” Phys. Rev. A, vol. 38, pp. 3098–3100, 1988.
• [18] C. Lee, W. Yang and R. G. Parr, “Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density,” Phys. Rev. B, vol. 37, pp. 785–789, 1988.
• [19] J. P. Merrick, D. Moran and L. Radom, “An evaluation of harmonic vibrational frequency scale fac-tors,” J. Phys. Chem. A, vol. 111, pp. 11683-11700, 2007.
• [20] R. Bauernschmitt and R. Ahlrichs, “Treatment of electronic excitations within the adiabatic approx-imation of time dependent density functional theory,” Chem. Phys. Lett., vol. 256, pp. 454–464, 1996.
• [21] M. E. Casida, C. Jamorski, K. C. Casida and D. R. Salahub, “Molecular excitation energies to high-lying bound states from time-dependent density-functional response theory: characterization and correction of the time-dependent local density approximation ionization threshold,” J. Chem. Phys., vol. 108, pp. 4439–4450, 1998.
• [22] N. M. O'Boyle, A. L. Tenderholt and K. M. Langner, “cclib: a library for package-independent com-putational chemistry algorithms,” J. Comput. Chem., vol. 29, pp. 839–845, 2008.
• [23] R. Ditchfield, “Molecular orbital theory of magnetic shielding and magnetic susceptibility,” J. Chem. Phys., vol. 56, pp. 5688–5691, 1972.
• [24] K. Wolinski, J. F. Hinton and P. Pulay, “Efficient implementation of the gauge-independent atomic orbital method for NMR chemical shift calculations,” J. Am. Chem. Soc., vol. 112, pp. 8251–8260, 1990.
• [25] A. Daina, O. Michielin and V. Zoete, “SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules,” Sci. Rep., vol. 7, no. 1, pp. 1-13, 2017.
• [26] P. Banerjee, O. A. Eckert, A. K. Schrey and R. Preissner, “ProTox-II: a webserver for the prediction of toxicity of chemicals,” Nucleic Acids Res. (Web server issue 2018).
• [27] C. Li, T. Zhang, Z. Zeng, X. Liu, Y. Zhao, B. Zhang and Y. Feng, “A New Route to Indazolone via Amidation Reaction of o-Carboxyazobenzene,” Org. Lett., vol. 14, No. 2, pp. 479–481, 2012.
• [28] S. Riaz, A. Jabbar, Ambreen, S. Khaskheli, S. Sagheer and M. I. Choudhary, “Anthraquinone based anti-UV acid-azo dyes; a study of their synthesis, fastness, and UV-protection properties,” J. Mol. Struct., vol. 1272, 134219, 2023
• [29] H. F. Huang, W. Ma, B. T. Tang and S. F. Zhang, “Properties of a novel acid dye 1-amino-4-[(6-nitro-2-benzothiazolyl)amino]-9,10-anthraquinone-2-sulfonic acid with anti-UV capability,” Chin. Chem. Lett., vol. 21 pp. 417–420, 2010.
• [30] H. Pajouhesh and G. R. Lenz, “Medicinal Chemical Properties of Successful Central Nervous Sys-tem Drugs, NeuroRx,” J. Am. Soc. Exp. NeuroTher., vol. 2, pp. 541–553, October 2005.
• [31] A. Mermer and S. Alyar, “Synthesis, characterization, DFT calculation, antioxidant activity, AD-MET and molecular docking of thiosemicarbazide derivatives and their Cu II) complexes,” Chem.-Biol. Interact., vol. 351, 109742, 2022
• [32] A. Daina and V. Zoete, “A boiled-egg to predict gastrointestinal absorption and brain penetration of small molecules,” ChemMedChem, vol. 11, pp. 1117-1121, 2016