شیمى کاربردى روز

شیمى کاربردى روز

سنتز و شناسایی ترکیبات جدید فسفرآمید و مطالعه اثر بازدارندگی آنها در مقابل ویروس‌های کرونا و آبله میمون با استفاده از روش داکینگ مولکولی

نوع مقاله : مقاله علمی پژوهشی

نویسندگان
دانشکده شیمی، دانشگاه سمنان، سمنان، ایران
چکیده
در چند سال اخیر، دو بیماری ویروسی-عفونی کرونا و آبله میمون و تهیه ترکیبات با خاصیت بیولوژیکی مناسب به عنوان دارو جهت بازدارندگی و مقابله با این بیماری‌ها توجه جامعه پزشکی و سازمان جهانی بهداشت را به خود جلب کرده است. از جمله ترکیبات شیمیایی که تاکنون خاصیت بیولوژیکی و دارویی مناسبی در برابر انواع بیماری‌ها از جمله سرطان، هپاتیت و کرونا از خود نشان داده‌اند، ترکیبات فسفرآمیدی با اسکلت اصلی O═P─N می‌باشند. از این رو، در کار حاضر، سه ترکیب جدید فسفرآمیدی شامل [OCH2C(CH3)2CH2O]P(═O)[NHC6H4(3-F))] (ترکیب ۱)، [(4-Cl)C6H4O]P(═O)[3-(NH)C5H4N]2 (ترکیب ۲) و [(3-F)C6H4NH]P(═O)[2-(NH)C5H4N]2 (ترکیب ۳) تهیه و شناسایی شدند و به‌عنوان مدل‌ برای انجام شبیه‌سازی داکینگ مولکولی جهت پیش‌بینی اثر بازدارندگی این ترکب‌ها در مقابل دو ویروس‌ کرونا (پروتئین‌ها با کدهای 6LU7 و 6M03) و آبله میمون (4QWO و 8CER) مورد استفاده قرار گرفتند. یافته‌ها نشان می‌دهند که ترکیب‌های مورد مطالعه با دارا بودن میل اتصال نسبتا بالا به گیرنده‌های پروتئینیِ ویروس کرونا (با انرژی‌های اتصال حدود ۷– کیلوکالری بر مول) می‌توانند در مهار ویروس کرونا مؤثر باشند. در مورد ویروس آبله میمون، انرژی‌های اتصال پروتئین-لیگاند مقادیر منفی (حدود ۸– کیلوکالری بر مول) را نشان می‌دهند که تائیدکننده اتصال پایدار و مطلوب بین پروتئین هدف با لیگاند است. بنابراین، ترکیبات مورد مطالعه 1 تا 3 می‌توانند به عنوان کاندید برای مقابله با ویروس‌ آبله میمون پیشنهاد شوند.
کلیدواژه‌ها
موضوعات

عنوان مقاله English

Synthesis and Characterization of New Phosphoramide Compounds and Study of Their Inhibitory Effects Against Corona and Monkeypox Viruses by using Molecular Docking Method

نویسندگان English

Zeinab Gholamrezaeia
Atekeh Tarahhomi
Department of Chemistry, Semnan University, Semnan, Iran
چکیده English

In recent years, two infectious viral diseases, Corona and Monkeypox, and preparation of compounds with suitable biological properties as drugs to inhibit these diseases have attracted attention of the medical community and World Health Organization. Phosphoramide compounds with the main O═P—N skeleton are among chemical compounds that have shown appropriate biological and medicinal properties to treat with various diseases such as cancer, hepatitis and corona. In present work, three new phosphoramide compounds including [OCH2C(CH3)2CH2O]P(═O)[NHC6H4(3-F)] (compound 1), [(4-Cl)C6H4O]P(═O)[3-(NH)C5H4N]2 (compound 2) and
[(3-F)C6H4NH]P(═O)[2-(NH)C5H4N]2 (compound 3) were prepared and characterized, and were used as model for molecular docking simulation to predict their potential inhibitory against corona (PDB IDs: 6LU7 and 6M03) and monkeypox (4QWO and 8CER) viruses. Obtained results show that the studied compounds having relatively high binding affinity with protein receptors of coronaviruse (with binding energies of about 7 kcal/mol) can be effective to control coronavirus. In the case of monkeypox, binding energies of ligand-protein complex (about 8 kcal/mol) illustrate negative values showing a stable and favorable binding connection between target protein with ligand. So, the studied compounds 1 – 3 can be suggested as candidates to inhibit corona and monkeypox viruses.

کلیدواژه‌ها English

Phosphoramide
Coronavirus
Monkeypox
Molecular docking
[1] Miyamoto, T., Kasagami, T., Asai, M., and Yamamoto, I. (1999) A novel bioactivation mechanism of phosphoramidate insecticides. Pestic. Biochem. Physiol. 63, 151-162.
[2] Čadež, T., Kolić, D., Šinko, G., and Kovarik, Z. (2021) Assessment of four organophosphorus pesticides as inhibitors of human acetylcholinesterase and butyrylcholinesterase. Sci. Rep. 11, 21486.
[3] Wang, J.-S., Zhao, H.-B., Ge, X.-G., Liu, Y., Chen, L., Wang, D.-Y., and Wang, Y.-Z. (2010) Novel flame-retardant and antidripping branched polyesters prepared via phosphorus-containing ionic monomer as end-capping agent. Ind. Eng. Chem. Res. 49, 4190-4196.
[4] Yan, J., Bu, J., Bai, X., Li, J., Ren, T., and Zhao, Y. (2012) The tribological study of novel phosphorous–nitrogen type phosphoramidate additives in rapeseed oil. Proc. IME J. J. Eng. Tribol. 226, 377-388.
[5] Abraham, T. W., Kalman, T. I., McIntee, E. J., and Wagner, C. R. (1996) Synthesis and biological activity of aromatic amino acid phosphoramidates of 5-fluoro-2‘-deoxyuridine and 1-β-arabinofuranosylcytosine: evidence of phosphoramidase activity. J. Med. Chem. 39, 4569-4575.
[6] Zhang, W., Fan, W., Zhou, Z., and Garrison, J. (2017) Synthesis and evaluation of radiolabeled phosphoramide mustard with selectivity for hypoxic cancer cells. ACS Med. Chem. Lett. 8, 1269-1274.
[7] Najarianzadeh, M., Tarahhomi, A., Pishgo, S., and van Der Lee, A. (2022) Experimental and theoretical study of novel amino-functionalized P(V) coordination compounds suggested as inhibitor of MPro of SARS-CoV-2 by molecular docking study. Appl. Organomet. Chem. 36, e6636.
[8] Yu, M., Chen, L., Jiang, F., Zhou, K., Liu, C., Sun, C., Li, X., Yang, Y., and Hong, M. (2017) Cation-induced strategy toward an hourglass-shaped Cu6I7–cluster and its color-tunable luminescence. Chem. Mater. 29, 8093-8099.
[9] Xu, X., Yao, Y., Zhang, Y., and Shen, Q. (2007) Synthesis, reactivity, and structural characterization of sodium and ytterbium complexes containing new imidazolidine-bridged bis (phenolato) ligands. Inorg. Chem. 46, 3743-3751.
[10] Kepert, D. L., Patrick, J. M., and White, A. H. (1983) Structure and Stereochemistry in f-Block Complexes of High Co-ordination Number. Part 3. The [M(bidentate ligand)2(unidentate ligand)4] System: Crystal Structures of Tetrakis (isothiocyanato)bis(octamethylpyrophosphoramide-OO")uranium(IV) and tetrachlorobis(octamethylpyrophosphoramide-OO")thorium(IV). J. Chem. Soc. Dalton Trans, 559.
[11] Furqan, M. M., Verma, B. R., Cremer, P. C., Imazio, M., and Klein, A. L. (2021) Pericardial diseases in COVID19: a contemporary review. Curr. Cardiol. Rep. 23, 90.
[12] Wang, D., Hu, B., Hu, C., Zhu, F., Liu, X., Zhang, J., Wang, B., Xiang, H., Cheng, Z., and Xiong, Y. (2020) Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. Jama 323, 1061-1069.
[13] Jabri, A., Kalra, A., Kumar, A., Alameh, A., Adroja, S., Bashir, H., Nowacki, A. S., Shah, R., Khubber, S., and Anmar, K. N. (2020) Incidence of stress cardiomyopathy during the coronavirus disease 2019 pandemic. JAMA Netw. Open 3, e2014780-e2014780.
[14] Giorgi, F. M., Pozzobon, D., Di Meglio, A., and Mercatelli, D. (2022) Genomic analysis of the recent monkeypox outbreak. Biorxiv, https://doi.org/10.1101/2022.06.01.494368.
[15] Ferdous, J., Barek, M. A., Hossen, M. S., Bhowmik, K. K., and Islam, M. S. (2023) A review on monkeypox virus outbreak: New challenge for world. Health Sci. Rep. 6, e1007.
[16] Agu, P., Afiukwa, C., Orji, O., Ezeh, E., Ofoke, I., Ogbu, C., Ugwuja, E., and Aja, P. (2023) Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in diseases management. Sci. Rep. 13, 13398.
[17] Meng, X.-Y., Zhang, H.-X., Mezei, M., and Cui, M. (2011) Molecular docking: a powerful approach for structure-based drug discovery. Curr. Comput.-Aided Drug Des., 146-157.
[18] Trott, O., and Olson, A. J. (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, 455-461.
[19] Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., and Ferrin, T. E. (2004) UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605-1612.
[20] Heidari, N., Tarahhomi, A., and van der Lee, A. (2022) Structural and molecular packing study of three new amidophosphoric acid esters and assessment of their inhibiting activity against SARS-CoV-2 by molecular docking. ChemSelect 7, e202201504.
[21] Tarahhomi, A., van Der Lee, A., and Ośmiałowski, B. (2019) A detailed theoretical and experimental study on the N-H, P═O and C═O stretching frequencies in two new phosphoric triamides and a statistical comparison with analogous structures. Polyhedron 158, 215-224.
[22] Khorram, M., Tarahhomi, A., van der Lee, A., and Excoffier, G. (2023) Structural, Hirshfeld surface and molecular docking studies of a new organotin(IV)-phosphoric triamide complex and an amidophosphoric acid ester proposed as possible SARS-CoV-2 and Monkeypox inhibitors. Heliyon 9.
[23] Srivastava, A. K., Divya, P., Praveenkumar, B., and Boomishankar, R. (2015) Potentially Ferroelectric {CuIIL2} n Based Two-Dimensional Framework Exhibiting High Polarization and Guest-Assisted Dielectric Anomaly. Chem. Mat. 27, 5222-5229.
[24] Najarianzadeh, M., Tarahhomi, A., Pishgo, S., and van der Lee, A. (2022) Experimental and theoretical study of novel amino-functionalized P(V) coordination compounds suggested as inhibitor of MPro of SARS-COV-2 by molecular docking study. Appl. Organomet. Chem. 36, e6636.
[25] Albobaledi, Z., Tarahhomi, A., Khaleghian, A., van der Lee, A., and Excoffier, G. (2024) Novel Co2+ and Cd2+ complexes derived from a new N-donor pyridyl-functionalized thiophosphoric triamide ligand: structural investigation, DNA/COVID-19/Monkeypox molecular docking, and biological assays. Appl. Organomet. Chem. 38, e7750.
[26] Deshpande, R. R., Tiwari, A. P., Nyayanit, N., and Modak, M. (2020) In silico molecular docking analysis for repurposing therapeutics against multiple proteins from SARS-CoV-2. Eur. J. Pharmacol. 886, 173430.
[27] Mohapatra, R. K., Mahal, A., Ansari, A., Kumar, M., Guru, J. P., Sarangi , A. K., Abdou, A., Mishra, S., Aljeldah, M., AlShehail, B. M., Alissa, M., Garout, M., Alsayyah A., Alshehri, A. A., Saif, A., Alqahtani, A., Alshehri, F. A., Alamri, A. A., Rabaan, A. A. (2023) Molecular docking and in-silico analysis of natural biomolecules against dengue, ebola, zika, SARS-CoV-2 variants of concern and monkeypox virus. J. Biosaf. Biosecurity. 5, 118-132.