Investigation of the Structural and Electronic Properties of the Novel Synthesized Methyl 2-(2-oxo-2H-chromen-4-ylamino) benzoate Compound by DFT Method and Evaluation of its Anti-Leishmania Agent Potential by Molecular Docking Study

Abstract

Leishmaniasis is a disease caused by different species of the leishmania parasite, transmitted through the sandfly, within the group of protozoa. According to the World Health Organization, leishmaniasis is one of the most encountered seven tropical diseases. Trypanothione reductase is a vital enzyme for the parasite. This has made Trypanothione reductase a potential target in the treatment of leishmaniasis. The limitations of current therapeutic options and the high cost have increased the motivation for research on the inhibition of Trypanothione reductase. In this study, the structural and electronic properties of the newly synthesized compound methyl 2-(2-oxo-2H-chromen-4-ylamino) benzoate were calculated using DFT/B3LYP and 6-311++G(d,p) basis set. The calculated structural parameters were found to be highly compatible when compared with experimental studies. The crystal packing of the compound was examined through the Hirshfeld surface analysis method. When the potential of the compound to be used as a drug was evaluated using Lipinski criteria, no hindrance to its use in living organisms was found. As the crystal structure of the enzyme was unknown, homology modeling was performed. Finally, in the molecular docking study, the interaction mechanisms of the compound mentioned in the title and the compound clomipramine used as a control in the receptor's active site were examined. The results revealed that the compound mentioned in the title demonstrated a better potential compared to the control compound.

Keywords

• Anti-Leishmaniasis
• DFT
• Hirsfeld surface analysis
• Drug-likeness
• Molecular docking

Supporting Institution

This study was supported by project number (Grant No: 2013FBE013)

References

1. Barakat, A., Islam, M.S., Ali, M., Al-Majid, A.M., Alshahrani, S., Alamary, A.S., Yousuf, S., … & Choudhary, M.I. (2021). Regio-and stereoselective synthesis of a new series of spirooxindole pyrrolidine grafted thiochromene scaffolds as potential anticancer agents. Symmetry, 13(8): 1426.
2. Biovia DS, (2020). BIOVIA discovery studio. Dassault Systèmes.
3. Breda, S., Reva, I., Lapinski, L., Nowak, M., & Fausto, R. (2006). Infrared spectra of pyrazine, pyrimidine and pyridazine in solid argon. Journal of Molecular Structure, 786(2-3): 193-206.
4. Cui, S-L., Wang, J., & Wang, Y-G. (2008). Efficient synthesis of 2-imino-1, 2-dihydroquinolines and 2-imino-thiochromenes via copper-catalyzed domino reaction. Tetrahedron, 64(3): 487-492.
5. Frisch, E., Hratchian, H.P., & Dennington, R. (2009). Gaussview, Version 5.0. 8. Gaussian. Inc. Wallingford CT.
6. Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Mennucci, B., Petersson, G.A., Nakatsuji, H., Caricato, M., … & Li, X. (2009). Gaussian 09, Revision C.01. Gaussian, Inc., Wallingford, CT.
7. Govindarao, K., Srinivasan, N., Suresh, R., Raheja, R., Annadurai, S., Bhandare, R.R., & Shaik, A.B. (2022). Quinoline conjugated 2-azetidinone derivatives as prospective anti-breast cancer agents: In vitro antiproliferative and anti-EGFR activities, molecular docking and in-silico drug likeliness studies. Journal of Saudi Chemical Society, 26(3): 101471.
8. Harris, R., Olson, A.J., & Goodsell, D.S. (2008). Automated prediction of ligand‐binding sites in proteins. Proteins: structure, function, and bioinformatics, 70(4): 1506-1517.

9. Lee, M.J., Albert, S.Y., Gardino, A.K., Heijink, A.M., Sorger, P.K., MacBeath, G., & Yaffe, MB. (2012). Sequential application of anticancer drugs enhances cell death by rewiring apoptotic signaling networks. Cell, 149(4): 780-794.
10. Lipinski, C.A. (2004). Lead-and drug-like compounds: the rule-of-five revolution. Drug discovery today: Technologies, 1(4): 337-341.
11. Luque-Agudo, V., Albarrán-Velo, J., Fernández-Bolaños, J., López, O., Light, M., Padrón, J., Lagunes, I., Román, E., Serrano, J., & Gil, M. (2017). Synthesis and antiproliferative activity of sulfa-Michael adducts and thiochromenes derived from carbohydrates. New Journal of Chemistry, 41(8): 3154-3162.
12. Ortiz, C., Echeverri, F., Robledo, S., Lanari, D., Curini, M., Quiñones, W., & Vargas, E. (2020). Synthesis and Evaluation of Antileishmanial and Cytotoxic Activity of Benzothiopyrane Derivatives. Molecules, 25(4): 800.
13. Pham, C.T., Mac, D.H., & Bui, T.T.T. (2019). Crystal structures of 2-(2-bromo-5-fluorophenyl)-8-ethoxy-3-nitro-2H-thiochromene and 2-(2-bromo-5-fluorophenyl)-7-methoxy-3-nitro-2H-thiochromene. Acta Crystallographica Section E: Crystallographic Communications, 75(11): 1783-1786.
14. Puppala, M., Zhao, X., Casemore, D., Zhou, B., Aridoss, G., Narayanapillai, S., & Xing, C. (2016). 4H-Chromene-based anticancer agents towards multi-drug resistant HL60/MX2 human leukemia: SAR at the 4th and 6th positions. Bioorganic & medicinal chemistry, 24(6): 1292-1297.
15. Roy, R., Rakshit, S., Bhowmik, T., Khan, S., Ghatak, A., & Bhar, S. (2014). Substituted 3-E-styryl-2 H-chromenes and 3-E-styryl-2 H-thiochromenes: synthesis, photophysical studies, anticancer activity, and exploration to tricyclic benzopyran skeleton. The Journal of Organic Chemistry, 79(14): 6603-6614.
16. Sajadikhah, S.S., & Nassiri, M. (2021). Synthesis of 2H-thiochromene derivatives (microreview). Chemistry of Heterocyclic Compounds, 57(11): 1073-1075.
17. Shahidha, R., Al-Saadi, A.A., & Muthu, S. (2015). Vibrational spectroscopic studies, normal co-ordinate analysis, first order hyperpolarizability, HOMO–LUMO of midodrine by using density functional methods. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 134127-142.
18. Singh, S.K., Yadav, M.S., Singh, A.S., Agrahari, A.K., Mishra, N., Kumar, S., & Tiwari, V.K. (2021). d-Glucosamine as the Green Ligand for Cu (I)-Catalyzed Regio-and Stereoselective Domino Synthesis of (Z)-3-Methyleneisoindoline-1-ones and (E)-N-Aryl-4 H-thiochromen-4-imines. ACS omega, 6(32): 21125-21138.
19. Spackman, M.A., & McKinnon, J.J. (2002). Fingerprinting intermolecular interactions in molecular crystals. CrystEngComm, 4(66): 378-392.
20. Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 71(3): 209-249.
21. Tasli, P.T., Soganci, T., Kart, S.O., Kart, H.H., & Ak, M. (2021). Quantum mechanical calculations of different monomeric structures with the same electroactive group to clarify the relationship between structure and ultimate optical and electrochemical properties of their conjugated polymers. Journal of Physics and Chemistry of Solids, 149109720.
22. Wolff, S., Grimwood, D., McKinnon, J., Turner, M., Jayatilaka, D., & Spackman, M. (2012). CrystalExplorer (Version 3.1). University of Western Australia.
23. Zhang, H., Berezov, A., Wang, Q., Zhang, G., Drebin, J., Murali, R., & Greene, M.I. (2007). ErbB receptors: from oncogenes to targeted cancer therapies. The Journal of clinical investigation, 117(8): 2051-2058.