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Bioactivity and quantum chemical calculations оf a new coumarine derivative as a strong antioxidant, antimicrobial and anti-cancer substance

Authors

  • Pelin Koparir Firat University, Vocational School, Department of Forensics Chemistry, 23169 Elazig

DOI:

https://doi.org/10.20450/mjcce.2023.2554

Keywords:

New coumarin; NMR; Computational calculations Docking; Biological activity

Abstract

4-(((4-Ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl)thio)methyl)-7-methyl-coumarin was synthesized, and its characterization was done with quantum chemical calculations and spectral techniques. The density functional method (B3LYP) with the 6-311G(d,p) basis set was used to calculate the molecular geometry, vibrational frequencies, and gauge, including atomic orbital (GIAO) 1H and 13C-NMR chemical shift values of the title compound in the ground state. The theoretical vibrational frequencies and chemical shift values agree well with the experimental results. DFT calculations of the density of states (DOS) and frontier molecular orbitals of the title compound were carried out at the B3LYP/6-311G(d,p) level of theory. In the present study, biological activities and molecular docking studies of this triazole ring containing coumarin derivative compound were carried out. Interactions with important residues in active sites were detected in molecular docking studies. In addition, in vitro analysis has shown that anti-microorganism activity is especially effective against bacterial organisms such as E. coli, S. aureus, B. cereus, and fungal organisms such as C. albicans, C. tropicalis. Also, the antioxidant capacity of the test compound was investigated by oxidative stress index (OSI) and radical scavenging power (DPPH.), and its antioxidant potential was found. In addition, it was determined by in vitro anticancer and SDS-PAGE analysis that the test compound does not cause a detrimental cytotoxic effect on healthy cell cultures such as HUVEC and has the potential for anticarcinogenic activity on MCF-7 and MKN-45 cancerous cell cultures.

References

(1) Borges, F.; Roleira, F.; Milhazes, N.; Santana, L., Uriarte. Simple coumarins and analogues in medicinal chemistry: occurrence, synthesis and biological activity. Curr. Med. Chem. 2005, 12, 887–916.

DOI: 10.2174/0929867053507315

(2) Borges Bubols, G.; Rocha Vianna, D.; Medina-Remon, A.; Von Poser, G.; Maria Lamuela-Raventos, R.; Lucia Eifler-Lima, V.; Cristina Garcia, S., The antioxidant activity of coumarins and flavonoids. Mini Rev. Med. Chem. 2013, 13, 318–334.

DOI: 10.2174/138955713804999775

(3) Davis, R. A.; Vullo, D.; Maresca, A.; Supuran, C. T.; Poulsen, S. A., Natural product coumarins that ınhibit human carbonic anhydrases. Bioorg. Med. Chem. 2013, 21, 1539–1543. DOI: 10.1016/j.bmc.2012.07.021

(4) Zhang, L.; Jiang, G.; Yao, F.; He, Y.; Liang, G.; Zhang, Y.; Hu, B.; Wu, Y.; Lİ, Y.; Liu, H., Growth inhibition and apoptosis ınduced by osthole, a natural coumarin, in hepatocellular carcinoma. PloS one. 2012, 7, e37865. DOI: 10.1371/journal.pone.0037865

(5) Peng, X. M.; Damu, G. L. V.; Zhou, H., Current developments of coumarin compounds in medicinal chemistry. Curr. Pharm. Des. 2013, 19, 3884–3930. DOI: 10.2174/1381612811319210013

(6) Thakur, A.; Singla, R.; Jaitak, V., Coumarins as anticancer agents: a review on synthetic strategies, mechanism of action and SAR studies. Eur. J. Med. Chem. 2015, 101, 476–495.

DOI: 10.1002/CHIN.201541254

(7) Karataş, M. O.; Uslu, H.; Sarı, S.; Alagöz, M. A.; Karakurt, A.; Alıcı, B.; Bilen, C.; Yavuz, E.; Gencer, N.; Arslan, O., Coumarin or benzoxazinone based novel carbonic anhydrase inhibitors: Synthesis, molecular docking and anticonvulsant studies. J. Enzyme. Inhib. Med. Chem. 2016, 31, 760–772.

DOI: 10.3109/14756366.2015.1063624

(8) Karataş, M. O.; Uslu, H.; Alici, B.; Gökçe, B.; Gencer, N.; Arslan, O., Some coumarins and benzoxazinones as potent paraoxonase 1 inhibitors. J. Enzyme. Inhib. Med. Chem. 2016, 31, 1386–1391.

DOI: 10.3109/14756366.2015.1063624

(9) Potdar, M. K.; Mohile, S. S.; Salunkhe, M. M., Coumarin syntheses via pechmann condensation in Lewis acidic chloroaluminate ionic liquid. Tetrahedron Lett. 2001, 42, 9285–9287. DOI: 10.1002/CHIN.200212169

(10) Perkin, W., XXIII On the hydride of aceto-salicyl. J. Chem. Soc. 1868, 21, 181–186.

DOI:10.1039/js8682100181

(11) Knoevenagel, E., Condensation of malonic acid with aromatic aldehydes with ammonia and amines. J. Am. Chem. Soc. 1898, 31, 2596–2619.

DOI: org/10.1002/cber.18980310308

(12) Karataş, M. O.; Uslu, H.; Alıcı, B.; Gökçe, B.; Gencer, N.; Arslan, O.; Arslan N. B.; Özdemir, N., Functionalized imidazolium and benzimidazolium salts as paraoxonase 1 inhibitors: synthesis, characterization and molecular docking studies. Bioorg. Med. Chem. 2016, 24, 1392–1401. DOI: 10.1016/j.bmc.2016.02.012

(13) Bayazeed, A.; Alshehrei, F.; Muhammad, Z. A.; Al-Fahemi, J.; El-Metwaly, N.; Farghaly, T. A., Synthesis of coumarin-analogues: analytical, spectral, conformational, MOE-docking and antimicrobial studies. Chemistry Select. 2020, 5, 1–1.

DOI: 10.1002/slct.201904724

(14) Koparir, P., Synthesis, antioxidant and antitumor activities of some of new cyclobutane containing triazoles derivatives. Phosphorus. Sulfur. Silicon. Relat. Elem. 2019, 194, 1028–1034.

DOI: 10.1080/10426507.2019.1597363

(15) Koparir, P.; Karaarslan, M.; Orek, C.; Koparir, M. Synthesis and in-vitro antimicrobial activity of novel aminophosphinic acids containing cyclobutane and 1, 3-thiazole. Phosphorus. Sulfur. Silicon. Relat. Elem. 2011, 186, 2368–2376.

DOI: 10.1080/10426507.2011.604660

(16) Parlak, A. E.; Tekin, S.; Karatepe, A.; Koparir, P.; Telceken, H.; CeribasıA. O.; Karatepe, M., In vitro and histological ınvestigation of antitumor effect of some triazole compounds in colon cancer cell line. J. Cell. Biochem. 2019, 120, 11809–11819.

DOI:org/10.1002/jcb.28460

(17) Blanco, M. T.; Cañadas, J.; García-Martos, P.; Marín, P.; García-Tapia, A.; Rodríguez, J., In vitro activities of posaconazole, fluconazole, ıtraconazole, ketoconazole and voriconazole against Candida glabrata. Rev. Esp. Quimioter. 2009, 22, 139–143.

(18) Saravolatz, L. D.; Johnson, L. B.; Kauffman, C. A., Voriconazole: a new triazole antifungal agent. Clinical Infectious Diseases. 2003, 36, 630–637.

DOI: 10.1086/367933

(19) Raj, R.; Gunasekaran, S.; Gnanasambandan, T.; Seshadri, S., Combined spectroscopic and DFT studies on 6-bromo-4-chloro-3-formyl coumarin. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2015, 139, 505–514. DOI:org/10.1016/j.saa.2014.12.024

(20) Koparir, M.; Orek, C.; Koparir, P.; Sarac, K., Synthesis, experimental, theoretical characterization and biological activities of 4-ethyl-5-(2-hydroxyphenyl)-2H-1,2,4-triazole-3(4H)-thione. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2013, 105, 522–531.

DOI: org/10.1016/j.saa.2012.12.052

(21) Cansiz, A.; Orek, C.; Koparir, M.; Koparir, P.; Cetin, A., 4-allyl-5-pyridin-4-yl-2, 4-dihydro-3H-1, 2, 4-triazole-3-thione: synthesis, experimental and theoretical characterization. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2012, 91, 136–145.

DOI:.org/10.1016/j.saa.2012.01.027

(22) Kalaiarasi, N.; Manivarman, S., Synthesis, spectroscopic characterization, computational exploration of 6-(2-(2, 4-dinitrophenylhydrazano)-tetrahydro-2-thioxopyrimidin-4 (1h)-one. Orient. J. Chem. 2017, 33, 304–317.

DOI: 10.13005/ojc/330136

(23) Inkaya, E.; Dinçer, M.; Çukurovalı, A.; Yılmaz, E., 2-chloro-N-[4-(3-methyl-3-phenylcyclobutyl)-1, 3-thiazol-2-yl]-N′-(naphthalen-1-ylmethylidene) acetohydrazide. Acta Crystallographica Section E: Structure reports online. 2011, 67, o310-o310.

DOI: org/10.1107/S1600536811000183

(24) Dinçer, M.; Özdemir, N.; Yılmaz, İ.; Çukurovalı, A.; Büyükgüngör, O., 1-methyl-1-phenyl-3-[1-hydroxyimino-2-(succinimido) ethyl] cyclobutane. Acta Crystallogr. C Struc. Chem. 2004, 60, o674–o676.

DOI: 10.1007/S11224-008-9387-7

(25) İnkaya, E.; Dinçer, M.; Ekici, Ö.; Cukurovali, A., 1-(3-methyl-3-mesityl)-cyclobutyl-2-(5-pyridin-4-yl-2H-[1,2,4] triazol-3-ylsulfanyl)-ethanone: X-ray structure, spectro¬scopic characterization and DFT studies. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2013, 101, 218–227. DOI: 10.1016/j.saa.2012.09.091

(26) Jameson, C. J.; Dios, A. C., A binitio calculations of the ıntermolecular chemical shift in nuclear magnetic resonance in the gas phase and for adsorbed species. J. Chem. Phys. 1992, 97, 417–434.

DOI: 10.1063/1.463586

(27) Orek, C.; Koparir, P.; Koparir, M., N-cyclohexyl-2- 5-(4-pyridyl)-4-(p-tolyl)-4H-1,2,4-triazol-3-ylsulfanyl -acetamide dihydrate: synthesis, experimental, theoretical characterization and biological activities. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2012, 97, 923–934. DOI:.org/10.1016/j.saa.2012.07.082

(28) Lin-Vien, D.; Colthup, N. B.; Fateley, W. G., Grasselli, J. G., The Handbook of İnfrared and Raman Characteristic Frequencies of Organic Molecules. Elsevier, 1991.

(29) Sarıkaya, E. K.; Dereli, Ö., Molecular structure and vibrational spectra of 7-methoxy-4-methylcoumarin by density functional method. J. Mol. Struct. 2013, 1052, 214–220. DOI: org/10.1016/j.molstruc.2013.08.024

(30) Moghanian, H.; Mobinikhaledi, A.; Monjezi, R., Synthesis, spectroscopy (vibrational, NMR and UV–vis) studies, HOMO–LUMO and NBO analysis of 8-formyl-7-hydroxy-4-methylcoumarin by ab initio calculations. J. Mol. Struct. 2013, 1052, 135–145.

DOI: org/10.1016/j.molstruc.2013.08.043

(31) Cansiz, A.; Cetin, A.; Kutulay P.; Koparir, M., Synthesis of tautomeric forms of 5-(2-hydroxyphenyl)-4-substituted-3H-1, 2, 4-triazole-3-thione. Asian J. Chem. 2009, 21, 617.

(32) Smith, B. C., Infrared Spectral İnterpretation: A Systematic Approach, CRC Press, 1998.

(33) Tammer, M.; Sokrates G., Infrared and Raman Characteristic Group Frequencies: Tables and Charts, Springer, 2004.

(34) Sarikaya, E. K.; Dereli, Ö.; Erdoğdu, Y.; Güllüoğlu, M., Molecular structure and vibrational spectra of 7-ethoxycoumarin by density functional method. J. Mol. Struct. 2013, 1049, 220–226.

DOI: org/10.1016/j.molstruc.2013.06.026

(35) Sajan, D.; Erdogdu, Y.; Reshmy, R.; Dereli, O.; Thomas K. K.; Joe, I. H., DFT-based molecular modeling, nbo analysis and vibrational spectroscopic study of 3-(bromoacetyl) coumarin. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2011, 82, 118–125.

DOI: 10.1016./j.saa.2011.07.013

(36) Chattaraj, P. K.; Giri, S., Stability, reactivity, and aromaticity of compounds of a multivalent superatom. J. Phys. Chem. A. 2007, 111, 11116–11121.

DOI: 10.1021/jp0760758

(37) Geerlings, P.; De Proft, F.; Langenaeker, W., Conceptual density functional theory. Chem. Rev. 2003, 103, 1793–1874. DOI: 10.1021/cr990029p

(38) Parr, R. G.; Pearson, R. G., Absolute hardness: companion parameter to absolute electronegativity. J. Am. Chem. Soc. 1983, 105, 7512–7516.

DOI: org/10.1021/ja00364a005

(39) Parr, R. G.; Szentpaly, L. V.; Liu, S., Electrophilicity index. J. Am. Chem. Soc. 1999, 121, 1922–1924.

DOI: org/10.1021/ja00364a005

(40) Pearson, R. G. Absolute Electronegativity and Hardness: Applications to Organic Chemistry. J. Org. Chem. 1989, 54, 1423–1430. DOI: org/10.1021/jo00267a034

(41) Pearson, R. G., Absolute electronegativity and hardness correlated with molecular orbital theory. Proc. Natl. Acad. Sci.U. 1986, 83, 8440–8441.

DOI: 10.1073/pnas.83.22.8440

(42) Awouafack, M. D.; McGaw, L. J.; Gottfried, S.; Mbouangouere, R.; Tane, P.; Spiteller, M.; Eloff, J. N., Antimicrobial activity and cytotoxicity of the ethanol extract, fractions and eight compounds isolated from Eriosema robustum (Fabaceae). BMC Complement Altern. Med. 2013, 13, 289.

DOI: 10.1186/1472-6882-13-289

(43) Di Guardo, A.; Sarac, M.; Gabardi, M.; Leonardis, D.; Solazzi, M.; Frisoli, A., Sensitivity analysis and identification of human parameters for an adaptive, underactuated hand exoskeleton. International Symposium on Advances in Robot Kinematics, Springer. 2018. DOI:10.1007/978-3-319-93188-3_51.

(44) Koparir, P.; Parlak, A. E.; Karatepe, A.; Omar, R. A., Elucidation of potential anticancer, antioxidant and antimicrobial properties of some new triazole compounds bearing pyridine-4-yl moiety and cyclobutane ring. Arab. J. Chem. 2022, 103957.

DOI: org/10.1016/j.arabjc.2022.103957

(45) Banbula, A.; Potempa, J.; Travis, J.; Fernandez-Catalén, C.; Mann, K.; Huber, R.; Bode, W.; Medrano, F. J., Amino-acid sequence and three-dimensional structure of the Staphylococcus aureus metalloproteinase at 1.72 å Resolut. Struct. 1998, 6, 1185–1193.

DOI:10.1016/S0969-2126(98)00118-X

(46) Juvvadi, P. R.; Fox, D.; Bobay, B. G.; Hoy, M. J.; Gobeil, S. M. C.; Venters, R. A.; Chang, Z.; Lin, J. J.; Averette, A. F.; Cole, D. C.; Barrington, B. C.; Wheaton, J. D.; Ciofani, M.; Trzoss, M.; Li, X.; Lee, S. C.; Chen, Y.-L.; Mutz, M.;. Spicer, L. D.; Schumacher, M. A.; Heitman, J.; Steinbach, W. J., Harnessing calcineurin-FK506-FKBP12 crystal structures from ınvasive fungal pathogens to develop antifungal agents. Nat. Commun. 2019, 10, 4275.

DOI: org/10.1038/s41467-019-12199-1

(47) Uddin, M.; Mustafa, F.; Rizvi, T. A.; Loney, T.; Suwaidi, H. A.; Al-Marzouqi, A. H. H.; Eldin, A. K.; Alsabeeha, N.; Adrian, T. E.; Stefanini, C., SARS-CoV-2/COVID-19: Viral genomics, epidemiology, vaccines, and therapeutic interventions. Viruses. 2020, 12, 526. DOI: org/10.3390/v12050526

(48) Cansiz, A.; Orek, C.; Koparir, M.; Koparir, P.; Cetin, A., 4-allyl-5-pyridin-4-yl-2,4-dihydro-3H-1,2,4-triazole-3-thione: synthesis experimental and theoretical characterization. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2012, 91, 136–145.

DOI:10.1016/j.saa.2012.01.02

(49) Dennington, R.; Keith, T. A.; Millam, J. M., GaussView. Shawnee Mission, KS., Semichem. Inc. 2009.

(50) Becke, A. D., Density‐functional thermochemistry. III. The role of exact exchange. J. Chem. Phys. 1993, 98, 5648–5652. DOI:10.1063/1.464913

(51) Omer, R. A.; Ahmed, L.; Koparir, M.; Koparir, P., Theoretical analysis of the reactivity of chloroquine and hydroxychloroquine. Indian J. Chem. 2020, 59, 1828–1834.

(52) Ahmed, L.; Omer, R. A., Computational study on paracetamol drug. J. Phys. Chem. Funct. Mater. 2020, 3, 9–13.

(53) Lee, C.; Yang, W.; Parr, R. G., Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys. Rev. B. 1988, 37, 785–789. DOI:10.1103/PhysRevB.37.785

(54) Wolinski, K.; Hinton, J. F.; Pulay, P., Efficient implementation of the gauge-ındependent atomic orbital method for NMR chemical shift calculations. J. Am. Chem. Soc. 1990, 112, 8251–8260.

DOI:10.1021/JA00179A005

(55) Rebaz, O.; Koparir, P.; Ahmed, L.; Koparir, M., Computational determination the reactivity of salbutamol and propranolol drugs. Turk. Comput. Theor. Chem. 2020, 4, 67–75.

DOI:org/10.33435/tcandtc.768758

(56) Sundaraganesan, N.; Ilakiamani, S.; Saleem, H.; Wojciechowski, P. M.; Michalska, D., FT-Raman and FT-IR spectra, vibrational assignments and density functional studies of 5-bromo-2-nitropyridine. spectrochim. Acta A Mol. Biomol. Spectrosc. 2005, 61, 2995–3001. DOI:10.1016/J.SAA.2004.11.016

(57) Jamróz, M. H., Vibrational energy distribution analysis (VEDA): Scopes and limitations. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2013, 114, 220–230.

DOI: 10.1016/j.saa.2013.05.096

(58) Morris, G. M.; Huey, R.; Lindstrom, W ; Sanner, M. F.; Belew, R. K.; Goodsell, D. S.; Olson, A. J., AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem. 2009, 30, 2785–2791. DOI: 10.1002/jcc.21256

(59) Trott, O.; Olson, A. J., AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput. Chem. 2010, 31, 455–461.

DOI:10.1002/jcc.21334

(60) Eloff, J. N., A Sensitive and quick microplate method to determine the minimal ınhibitory concentration of plant extracts for bacteria. Planta Med. 1998, 64, 711–713. DOI: 10.1055/s-2006-957563

(61) Wayne, P., Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, Approved Standard. CLSI document M27-A2. 2002.

(62) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard. 9th ed., Clinical and Laboratory Standards Institute, Wayne, PA, 2012.

(63) Saraç, H.; Demirbaş, A.; Daştan, S. D.; Ataş, M.; Çevik, Ö.; Eruygur, N., Evaluation of nutrients and biological activities of kenger (Gundellia tournefortii L.) seeds cultivated in Sivas Province. Turk. J. Agric. Food Sci. Technol. 2019, 7, 52–58.

DOI:10.24925/TURJAF.V7ISP2.52-58.3126

(64) Erel, O., A new automated colorimetric method for measuring total oxidant status. Clin. Biochem. 2005, 38, 1103–1111.

DOI:org/10.1016/j.clinbiochem.2005.08.008

(65) Hlavac, F.; Rouer, E., Expression of the protein–tyrosine kinase p56lckby the pTRX vector yields a highly soluble protein recovered by mild sonication. Protein Expr. Purif. 1997, 11, 227–232.

DOI: org/10.1006/prep.1997.0791

(66) Laemmli, U. K., Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970, 227, 680–685. DOI: 10.1038/227680a0

(67) Blois, M. S., Antioxidant determinations by the use of a stable free radical. Nature. 1958, 181, 1199–1200. DOI:.org/10.1038/1811199a0

(68) Koparir, P.; Sarac, K.;. Omar, R. A., Synthesis, molecular characterization, biological and computational studies of new molecule contain 1, 2, 4-triazole, and coumarin bearing 6, 8-dimethyl. Biointerface Res. Appl. Chem. 2022, 12, 809–823.

DOI:org/10.33263/BRIAC121.809823

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2023-05-11 — Updated on 2023-07-01

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Koparir, P. (2023). Bioactivity and quantum chemical calculations оf a new coumarine derivative as a strong antioxidant, antimicrobial and anti-cancer substance. Macedonian Journal of Chemistry and Chemical Engineering, 42(1). https://doi.org/10.20450/mjcce.2023.2554 (Original work published May 11, 2023)

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Organic Chemistry