Login Register Cart 0
Generic placeholder image

Current Computer-Aided Drug Design

Editor-in-Chief

ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Synthesis, Docking Study of Some Novel Chromeno[4',3'-b]Pyrano [6,5-d]Pyrimidine Derivatives Against COVID-19 Main Protease (Mpro) (6LU7, 6M03)

Author(s): Radineh Motamedi*, Safieh Soufian, Zahra Rostami Ghalhar, Mahdiyeh Jalali and Hooman Rahimi

Volume 20, Issue 5, 2024

Published on: 08 June, 2023

Page: [551 - 563] Pages: 13

DOI: 10.2174/1573409919666230529125038

Price: $65

conference banner
Abstract

Aims: In this work, some new chromeno[4',3'-b]pyrano[6,5-d]pyrimidines,3-amino and 3-methyl-5-aryl-4-imino-5(H)-chromeno[4',3'-b]pyrano[6,5-d]pyrimidine-6-ones derivatives were synthesized.

Background: Chromenopyrimidines have attracted significant attention recently because of their activities, such as antiviral and cytotoxic activity.

Objective: All synthesized compounds were characterized using IR, 1H-NMR, Mass Spectroscopy, and elemental analysis data.

Methods: Molecular docking studies were carried out to determine the inhibitory action of studied ligands against the Main Protease (6LU7, 6m03) of coronavirus (COVID-19). Moreover, the Lipinski Rule parameters were calculated for the synthesized compounds.

Results: The result of the docking studies showed a significant inhibitory action against the Main protease (Mpro) of SARS-CoV-2, and the binding energy (ΔG) values of the ligands against the protein (6LU7, 6M03) are -7.8 to -9.9 Kcal/mole.

Conclusion: It may conclude that some ligands were likely to be considered lead-like against the main protease of SARS-CoV-2.

Keywords: Chromeno[4', 3'-b]pyrano[6, 5-d]pyrimidines, 4-Hydroxy coumarin, molecular modeling, main protease, SARSCoV- 2, COVID-19.

« Previous Next »
Graphical Abstract

[1]
Dong, E.; Du, H.; Gardner, L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect. Dis., 2020, 20(5), 533-534.
[http://dx.doi.org/10.1016/S1473-3099(20)30120-1] [PMID: 32087114]
[2]
Senanayake, S.L. Drug repurposing strategies for COVID-19. Future Drug Discov., 2020, 0(0), fdd-2020-fdd-0010.
[http://dx.doi.org/10.4155/fdd-2020-0010]
[3]
Shamsi, A.; Mohammad, T.; Anwar, S.; AlAjmi, M.F.; Hussain, A.; Rehman, M.T.; Islam, A.; Hassan, M.I. Glecaprevir and Maraviroc are high-affinity inhibitors of SARS-CoV-2 main protease: possible implication in COVID-19 therapy. Biosci. Rep., 2020, 40(6), BSR20201256.
[http://dx.doi.org/10.1042/BSR20201256] [PMID: 32441299]
[4]
Sheahan, T.P.; Sims, A.C.; Leist, S.R.; Schäfer, A.; Won, J.; Brown, A.J.; Montgomery, S.A.; Hogg, A.; Babusis, D.; Clarke, M.O.; Spahn, J.E.; Bauer, L.; Sellers, S.; Porter, D.; Feng, J.Y.; Cihlar, T.; Jordan, R.; Denison, M.R.; Baric, R.S. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat. Commun., 2020, 11(1), 222.
[http://dx.doi.org/10.1038/s41467-019-13940-6] [PMID: 31924756]
[5]
Lan, J.; Ge, J.; Yu, J.; Shan, S.; Zhou, H.; Fan, S.; Zhang, Q.; Shi, X.; Wang, Q.; Zhang, L.; Wang, X. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature, 2020, 581(7807), 215-220.
[http://dx.doi.org/10.1038/s41586-020-2180-5] [PMID: 32225176]
[6]
Shirato, K.; Kawase, M.; Matsuyama, S. Middle East respiratory syndrome coronavirus infection mediated by the transmembrane serine protease TMPRSS2. J. Virol., 2013, 87(23), 12552-12561.
[http://dx.doi.org/10.1128/JVI.01890-13] [PMID: 24027332]
[7]
Jin, Z.; Du, X.; Xu, Y.; Deng, Y.; Liu, M.; Zhao, Y.; Zhang, B.; Li, X.; Zhang, L.; Peng, C.; Duan, Y.; Yu, J.; Wang, L.; Yang, K.; Liu, F.; Jiang, R.; Yang, X.; You, T.; Liu, X.; Yang, X.; Bai, F.; Liu, H.; Liu, X.; Guddat, L.W.; Xu, W.; Xiao, G.; Qin, C.; Shi, Z.; Jiang, H.; Rao, Z.; Yang, H. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature, 2020, 582(7811), 289-293.
[http://dx.doi.org/10.1038/s41586-020-2223-y] [PMID: 32272481]
[8]
Zhang, L.; Lin, D.; Sun, X.; Curth, U.; Drosten, C.; Sauerhering, L.; Becker, S.; Rox, K.; Hilgenfeld, R. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science, 2020, 368(6489), 409-412.
[http://dx.doi.org/10.1126/science.abb3405] [PMID: 32198291]
[9]
Bhat, A.R.; Dongre, R.S.; Naikoo, G.A.; Hassan, I.U.; Ara, T. Proficient synthesis of bioactive annulated pyrimidine derivatives: A review. J. Taibah Univ. Sci., 2017, 11(6), 1047-1069.
[http://dx.doi.org/10.1016/j.jtusci.2017.05.005]
[10]
Lagoja, I.M. Pyrimidine as constituent of natural biologically active compounds. Chem. Biodivers., 2005, 2(1), 1-50.
[http://dx.doi.org/10.1002/cbdv.200490173] [PMID: 17191918]
[11]
Alam, O.; Khan, S.A.; Siddiqui, N.; Ahsan, W.; Verma, S.P.; Gilani, S.J. Antihypertensive activity of newer 1,4-dihydro-5-pyrimidine carboxamides: Synthesis and pharmacological evaluation. Eur. J. Med. Chem., 2010, 45(11), 5113-5119.
[http://dx.doi.org/10.1016/j.ejmech.2010.08.022] [PMID: 20813434]
[12]
Bruno, O.; Brullo, C.; Ranise, A.; Schenone, S.; Bondavalli, F.; Barocelli, E.; Ballabeni, V.; Chiavarini, M.; Tognolini, M.; Impicciatore, M. Synthesis and pharmacological evaluation of 2,5-cycloamino-5H-[1]benzopyrano[4,3-d]pyrimidines endowed with in vitro antiplatelet activity. Bioorg. Med. Chem. Lett., 2001, 11(11), 1397-1400.
[http://dx.doi.org/10.1016/S0960-894X(01)00221-9] [PMID: 11378363]
[13]
Perlíková, P.; Hocek, M. Pyrrolo[2,3-d]pyrimidine (7-deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides. Med. Res. Rev., 2017, 37(6), 1429-1460.
[http://dx.doi.org/10.1002/med.21465] [PMID: 28834581]
[14]
Barakat, A.; Soliman, S.M.; Al-Majid, A.M.; Lotfy, G.; Ghabbour, H.A.; Fun, H.K.; Yousuf, S.; Choudhary, M.I.; Wadood, A. Synthesis and structure investigation of novel pyrimidine-2,4,6-trione derivatives of highly potential biological activity as anti-diabetic agent. J. Mol. Struct., 2015, 1098, 365-376.
[http://dx.doi.org/10.1016/j.molstruc.2015.06.037]
[15]
Padmaja, A.; Payani, T.; Reddy, G.D.; Padmavathi, V. Synthesis, antimicrobial and antioxidant activities of substituted pyrazoles, isoxazoles, pyrimidine and thioxopyrimidine derivatives. Eur. J. Med. Chem., 2009, 44(11), 4557-4566.
[http://dx.doi.org/10.1016/j.ejmech.2009.06.024] [PMID: 19631423]
[16]
Abozeid, M.A.; El-Kholany, M.R.; Abouzeid, L.A.; Abdel-Rahman, A.R.H.; El-Desoky, E-S.I. Synthesis and computational analysis of new antioxidant and antimicrobial angular chromenopyrimidines. J. Heterocycl. Chem., 2019, 56(10), 2922-2933.
[http://dx.doi.org/10.1002/jhet.3686]
[17]
Bingi, C.; Emmadi, N.R.; Chennapuram, M.; Poornachandra, Y.; Kumar, C.G.; Nanubolu, J.B.; Atmakur, K. One-pot catalyst free synthesis of novel kojic acid tagged 2-aryl/alkyl substituted-4H-chromenes and evaluation of their antimicrobial and anti-biofilm activities. Bioorg. Med. Chem. Lett., 2015, 25(9), 1915-1919.
[http://dx.doi.org/10.1016/j.bmcl.2015.03.034] [PMID: 25838145]
[18]
El-Desoky, S.I.; Badria, F.A.; Abozeid, M.A.; Kandeel, E.A.; Abdel-Rahman, A.H. Synthesis and antitumor studies of novel benzopyrano-1,2,3-selenadiazole and spiro[benzopyrano]-1,3,4-thiadia zoline derivatives. Med. Chem. Res., 2013, 22(5), 2105-2114.
[http://dx.doi.org/10.1007/s00044-012-0201-0]
[19]
Reddy, B.V.S.; Divya, B.; Swain, M.; Rao, T.P.; Yadav, J.S.; Vishnu Vardhan, M.V.P.S. A domino Knoevenagel hetero-Diels–Alder reaction for the synthesis of polycyclic chromene derivatives and evaluation of their cytotoxicity. Bioorg. Med. Chem. Lett., 2012, 22(5), 1995-1999.
[http://dx.doi.org/10.1016/j.bmcl.2012.01.033] [PMID: 22330634]
[20]
Bonacorso, H.G.; Rosa, W.C.; Oliveira, S.M.; Brusco, I.; Brum, E.S.; Rodrigues, M.B.; Frizzo, C.P.; Zanatta, N. Synthesis of novel trifluoromethyl-substituted spiro-[chromeno[4,3- d]pyrimidine-5,1′-cycloalkanes], and evaluation of their analgesic effects in a mouse pain model. Bioorg. Med. Chem. Lett., 2017, 27(7), 1551-1556.
[http://dx.doi.org/10.1016/j.bmcl.2017.02.036] [PMID: 28259627]
[21]
Bhosle, M.R.; Wahul, D.B.; Bondle, G.M.; Sarkate, A.; Tiwari, S.V. An efficient multicomponent synthesis and in vitro anticancer activity of dihydropyranochromene and chromenopyrimidine-2,5-diones. Synth. Commun., 2018, 48(16), 2046-2060.
[http://dx.doi.org/10.1080/00397911.2018.1480042]
[22]
Sabry, N.M.; Mohamed, H.M.; Khattab, E.S.A.E.H.; Motlaq, S.S.; El-Agrody, A.M. Synthesis of 4H-chromene, coumarin, 12H-chromeno[2,3-d]pyrimidine derivatives and some of their antimicrobial and cytotoxicity activities. Eur. J. Med. Chem., 2011, 46(2), 765-772.
[http://dx.doi.org/10.1016/j.ejmech.2010.12.015] [PMID: 21216502]
[23]
Miri, R.; Motamedi, R.; Rezaei, M.R.; Firuzi, O.; Javidnia, A.; Shafiee, A. Design, synthesis and evaluation of cytotoxicity of novel chromeno[4,3-b]quinoline derivatives. Arch. Pharm. (Weinheim), 2011, 344(2), 111-118.
[http://dx.doi.org/10.1002/ardp.201000196] [PMID: 21290427]
[24]
Motamedi, R. Synthesis of novel chromeno[4′,3′- b]pyrano[6,5- b]quinoline derivatives. Heterocycl. Commun., 2011, 17(5-6), 169-172.
[http://dx.doi.org/10.1515/HC.2011.047]
[25]
Motamedi, R. Solvent-free synthesis of novel 5-oxo-5H-chromeno [4,3-b]pyridine derivatives. Chem. Heterocycl. Compd., 2013, 48(12), 1839-1843.
[http://dx.doi.org/10.1007/s10593-013-1217-1]
[26]
Motamedi, R.; Shafiee, A.; Rezai, M.R.; Firuzi, O.; Edraki, N.; Miri, R. Oxidative aromatization, cytotoxic activity evaluation and conformational study of novel 7-aryl-10, 11-dihydro-7h-chromeno [4, 3-b]quinoline-6, 8(9h, 12h)-dione derivatives. Iran. J. Pharm. Res., 2014, 13(1), 103-114.
[PMID: 24734061]
[27]
Shafiee, A.; Motamedi, R.; Firuzi, O.; Meili, S.; Mehdipour, A.R.; Miri, R. Synthesis and cytotoxic activity of novel benzopyrano[3,2-c]chromene-6,8-dione derivatives. Med. Chem. Res., 2011, 20(4), 466-474.
[http://dx.doi.org/10.1007/s00044-010-9340-3]
[28]
Abdolmohammadi, S.; Balalaie, S. Novel and efficient catalysts for the one-pot synthesis of 3,4-dihydropyrano[c]chromene derivatives in aqueous media. Tetrahedron Lett., 2007, 48(18), 3299-3303.
[http://dx.doi.org/10.1016/j.tetlet.2007.02.135]
[29]
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(2), 455-461.
[PMID: 19499576]
[30]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings 1PII of original article: S0169-409X(96)00423-1. The article was originally published in Advanced Drug Delivery Reviews 23 (1997) 3–25. 1. Adv. Drug Deliv. Rev., 2001, 46(1-3), 3-26.
[http://dx.doi.org/10.1016/S0169-409X(00)00129-0] [PMID: 11259830]
[31]
Wang, R.; Fu, Y.; Lai, L. A new atom-additive method for calculating partition coefficients. J. Chem. Inf. Comput. Sci., 1997, 37(3), 615-621.
[http://dx.doi.org/10.1021/ci960169p]
[32]
Zhao, Y.H.; Abraham, M.H.; Le, J.; Hersey, A.; Luscombe, C.N.; Beck, G.; Sherborne, B.; Cooper, I. Rate-limited steps of human oral absorption and QSAR studies. Pharm. Res., 2002, 19(10), 1446-1457.
[http://dx.doi.org/10.1023/A:1020444330011] [PMID: 12425461]
[33]
Benedict, J. BIOVIA, discovery studio visualizer, 3D EXPERIENCE platform, release 2019; Dassault Systèmes: San Diego, 2020.
[34]
Natarajan, R.; Anthoni Samy, H.N.; Sivaperuman, A.; Subramani, A. Structure-activity relationships of pyrimidine derivatives and their biological activity-A review. Med. Chem., 2022, 19(1), 10-30.
[PMID: 35579151]

Rights & Permissions Print Cite
Article Metrics
29
3
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy