Kalirajan Rajagopal, R. Kannan, B. Aparna, P. Varakumar, A. Pandiselvi, B. Gowramma
firstname.lastname@example.org , email@example.com
Kalirajan Rajagopal*, R. Kannan, B. Aparna, P. Varakumar, A. Pandiselvi, B. Gowramma
Department of Pharmaceutical Chemistry, JSS College of Pharmacy (JSS Academy of Higher Education & Research), Ooty, The Nilgiris, Tamil Nadu, India.
Volume - 16,
Issue - 2,
Year - 2023
COVID-19 is affected in more than 200 countries in the world. In this article, some pyrazole bearing 9-anilinoacridines(1a-z) were designed by in-silico studies for SARS-CoV-2 Mpro inhibitory activity. The docking for 1a-z against SARS-CoV-2 Mpro (5R82.pdb) targeting corona virus using Schrodinger suit. The Glide module is used for docking, qikprop for in-silico ADMET screening and Prime MM-GB/SA to determine binding energy of ligands. From the results, many compounds are significantly binding with SARS-CoV-2 Mpro with high G-score when compared to one of the currently recommended drug for COVID19, Hydroxychloroquine (-5.47). From results, many compounds exhibited similar interactions with SARS-CoV-2 Mpro and the aminoacids between GLN19 and GLY143 plays major role for binding. The in-silico ADMET properties are within the recommended values. The MM-GBSA calculations for most of the potent inhibitors are stable. In conclusion, 1t,m,j,o are SARS-CoV-2 Mpro inhibitors and may be useful for significant COVID19 activity after further refinement.
Cite this article:
Kalirajan Rajagopal, R. Kannan, B. Aparna, P. Varakumar, A. Pandiselvi, B. Gowramma. COVID-19 Activity of Some 9-Anilinoacridines substituted with Pyrazole against SARS CoV2 Main Protease: An In-silico Approach. Research Journal of Pharmacy and Technology 2023; 16(2):529-4. doi: 10.52711/0974-360X.2023.00090
Kalirajan Rajagopal, R. Kannan, B. Aparna, P. Varakumar, A. Pandiselvi, B. Gowramma. COVID-19 Activity of Some 9-Anilinoacridines substituted with Pyrazole against SARS CoV2 Main Protease: An In-silico Approach. Research Journal of Pharmacy and Technology 2023; 16(2):529-4. doi: 10.52711/0974-360X.2023.00090 Available on: https://rjptonline.org/AbstractView.aspx?PID=2023-16-2-9
1. Wang D., Hu B., Hu C. Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA.; 2020, doi: 10.1001/jama.2020.1585.
2. Holshue M.L,. DeBolt C., Lindquist S, First Case of 2019 Novel Coronavirus in the United States. The New Engl J Med.; 2020, doi: 10.1056/NEJMoa2001191.
3. Yadi Zhou, Yuan Hou, Jiayu Shen, Yin Huang, William Martin, Feixiong Cheng, Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discovery. 2020, 6:14-18.
4. Gu J., Han B., Wang J., COVID-19: Gastrointestinal manifestations and potential fecal-oral transmission. Gastroenterology. 2020. doi: https://doi.org/10.1053/j.gastro.2020.02.054.
5. Calisher C., Carroll D., Colwell R., Corley R.B., Daszak P., Drosten C., Enjuanes L., Farrar J., Field H., Golding J., Statement in support of the scientists, public health professionals, and medical professionals of China combatting COVID-19. Lancet. 2020, 395(10226):42–43.
6. To K.K., Tsang O.T., Chik-Yan Yip C. Consistent detection of 2019 novel coronavirus in saliva. Clinical Infectious Diseases. 2020, doi: 10.1093/cid/ciaa149.
7. Lu R., Zhao X., Li J. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020, doi: 10.1016/S0140-6736(20)30251-8.
8. Zhou P., Yang X.L., Wang X.G. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020, doi: 10.1038/s41586-020-2012-7.
9. Huang Q., Herrman, A. Fast assessment of human receptor-binding capability of 2019 novel coronavirus (2019-nCoV). Bio Rxiv. 2020, doi: 10.1101/2020.02.01.930537
10. Zhang H., Kang Z.J., Gong H.Y., The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes. bioRxiv 927806. 2020, doi: 10.1101/2020.01.30.927806.
11. Kalirajan Rajagopal, Gowramma Byran, Srikanth Jupudi and R. Vadivelan. Activity of Phytochemical constituents of Black Pepper, Ginger and Garlic against Coronavirus (COVID19): An In-silico approach, Int J Health and Allied Sci. 2020, 9:S43- 50. DOI:10.4103/ijhas.IJHAS_55_20.
12. Rajagopal Kalirajan. Activity of some novel Chalcone substituted 9-anilinoacridines against Coronavirus (COVID19): A computational approach, Coronaviruses, 2020, 1(1):63-71. DOI : 10.2174/2666796701999200625210746.
13. Kalirajan Rajagopal, Potlapati Varakumar, Baliwada Aparna, Gowramma Byran and Srikanth Jupudi. Identification of some novel Oxazine substituted 9-anilinoacridines as SARS-CoV-2 inhibitors for COVID-19 by Molecular docking, Free energy calculation and molecular dynamics studies. J Biomol. Str Dyn. 2020, https://doi.org/10.1080/07391102.2020.1798285
14. Chang L., Yan Y., Wang L. Coronavirus Disease 2019: Coronaviruses and Blood Safety. Transfusion Med. Rev. 2020, https://doi.org/10.1016/j.tmrv.2020.02.003.
15. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y. Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China. Lancet. 2020, https://doi.org/10.1016/s0140-6736(20)30183-5.
16. Kalirajan R., Mohammed rafick M.H., Sankar S., Gowramma B. Green synthesis of some novel chalcone and isoxazole substituted 9-anilinoacridine derivatives and evaluation of their antimicrobial and larvicidal activities. Indian J Chem. 2018, 57B:583-90.
17. Gomathy Subramnian, Kalirajan Rajagopal, Farhath Sherin. Molecular Docking Studies, In silico ADMET Screening of Some Novel Thiazolidine Substituted Oxadiazoles as Sirtuin 3 Activators Targeting Parkinson’s Disease. Research J. Pharm. and Tech 2020; 13(6): 2708-2714. DOI: 10.5958/0974-360X.2020.00482.5
18. Kalirajan R., Muralidharan V., Jubie S., Gowramma B., Gomathy S., Sankar S., Elango K. Synthesis of some novel pyrazole substituted 9-anilinoacridine derivatives and evaluation for their antioxidant and cytotoxic activities. J Heterocycl Chem. 2012, 49:748-54.
19. Kalirajan R., Mohammed rafick M.H., Jubie S., Sankar S. Docking studies, synthesis, characterization and evaluation of their antioxidant and cytotoxic activities of some novel isoxazole substituted 9-anilinoacridine derivatives. The Sci World J. 2012, 165258, doi:10.1100/2012/165258.
20. Kalirajan R., Vivek kulshrestha, Sankar S., Jubie S. Docking studies, synthesis, characterization of some novel oxazine substituted 9-anilinoacridine derivatives and evaluation for their anti-oxidant and anticancer activities as topo isomerase II inhibitors. Eur J Med Chem. 2012,56,:217-224.
21. Kalirajan R,, Leela Rathore, Jubie S., Gowramma B., Gomathy S., Sankar S., Microwave assisted synthesis of some novel pyrazole substituted benzimidazoles and evaluation of their biological activities. Indian J Chem. 2011, 50B:1794-1801.
22. Kalirajan R., Sankar S., Jubie S., Gowramma B. Molecular Docking studies and in-silico ADMET Screening of Some novel Oxazine substituted 9-Anilinoacridines as Topoisomerase II Inhibitors. Indian J Pharm Edu and Res. 2017, 51(1):110-115.
23. Elizabeth Eldhose, Gowramma B., Manal Mohammed, Kalirajan R., Kaviarasan L., Translational Chemotherapy for triple negative Breast Cancer - A Review on significance of poly (ADP-ribose) polymerase 1 (PARP 1) inhibitors, Research J. Pharm. and Tech. 2019,12(6):3098-3104. doi: 10.5958/0974-360X.2019.00524.9.
24. Kalirajan R., Gaurav K., Pandiselvi A., Gowramm, B., Sanka, S. Novel Thiazine substituted 9-Anilinoacridines: Synthesis, Antitumour activity and Structure-Activity Relationships. Anti-Cancer Agents in Med Chem. 2019, 11:1350-1358. DOI :10.2174/1871520619666190408134224.
25. Kalirajan R., Vivek kulshrestha, Sankar S. Synthesis, Characterization and Evaluation for Antitumour Activity of Some Novel Oxazine Substituted 9-Anilinoacridines and their 3D-QSAR Studies. Indian J Pharm sci. 2018.80(5):921-929.
26. Kalirajan R., Pandiselvi A., Gowramma B., Balachandran P. In-silico design, ADMET screening, MM-GBSA binding free energy of some novel isoxazole substituted9-anilinoacridines as HER2 inhibitors targeting breast cancer. Current Drug Res Rev. 2019.11(2):118-128.
27. Nadaraj V., Selvi S.T., Mohan S. Microwave-induced synthesis and anti-microbial activities of 7,10,11,12-tetrahydrobenzo[c]acridin-8(9H)-one derivatives. Eur J Med Chem. 2009, 44:976-980.
28. Kapuriya N., Kapuriya K., Zhang X., Chou T.C., Kakadiya R, Synthesis and biological activity of stable and potent antitumor agents, aniline nitrogen mustards linked to 9-anilinoacridines via a urea linkage, Bioorg Med Chem. 2008, 16:5413-5423.
29. Yuan Wan Sun, Kuen Yuan Chen, Chul Hoon Kwon, Kun Ming Chen. CK0403. A 9 aminoacridine, is a potent anti cancer agent in human breast cancer cells. Mol Med Reports, 2016, 13:933-938.
30. Wakelin L.P.G., Bu X., Eleftheriou A., Parmar A., Hayek C., Stewart B.W. Bisintercalating threading diacridines: relationships between DNA binding, cytotoxicity, and cell cycle arrest, J Med Chem. 2003, 46(26):5790-5802.
31. Sondhi S.M., Johar M., Nirupama S., Sukla R., Raghubir R., Dastidar S.G. Synthesis of sulpha drug acridine derivatives and their evaluation for anti-anflammatory, analgesic and anticancer acvity. Indian J Chem, 2002, 41B:2659-2666,.
32. Dickens B.F., Weglicki W.B., Boehme P.A., Mak I.T. Antioxidant and lysosomotropic properties of acridine-propranolol: protection against oxidative endothelial cell injury. The J Mol CellCardiol. 2002, 34:129-137.
33. Anderson M.O., Sherrill J., Madrid P.B., Liou A.P., Weisman J.L., DeRisi J.L. Parallel synthesis of 9-aminoacridines and their evaluation against chloroquine-resistant Plasmodium falciparum. Bioorg Med Chem. 2006, 14:334-343.
34. Giorgio C.D., Shimi K., Boyer G., Delmas F., Galy J.P., Synthesis and antileishmanial activity of 6-mono-substituted and 3,6-di-substituted acridines obtained by acylation of proflavine. Eur J Med Chem. 2007,42:1277-1284.
35. Llama E.F., Campo C.D., Capo M., Anadon M. Synthesis and antinociceptive activity of 9-phenyl-oxy or 9-acyl-oxy derivatives of xanthene, thioxanthene and acridine. Eur J Med Chem. 1989, 24:391-396,.
36. Goodell J.R., Madhok A.A., Hiasa H., Ferguson D.M., Synthesis and evaluation of acridine- and acridone-based anti-herpes agents with topoisomerase activity. Bioorg Med Chem. 2006, 14:5467-80.
37. Rastogi K., Chang J.Y., Pan W.Y., Chen C.H., Chou T.C. Antitumor AHMA linked to DNA minor groove binding agents: synthesis and biological evaluation. J Med Chem. 2002, 45(20):4485-4493.
38. Kalirajan R., Sivakumar S.U., Jubie S., Gowramma B., Suresh B. Synthesis and biological evaluation of some heterocyclic derivatives of chalcones. Int J Chem tech res. 2009, 1(1): 27-34.
39. Kedar M.S, Shirbhate M.P, Rajani Chauhan, Suman Sharma, Amrita Verma. Design Synthesis and Evaluation of Anticancer Pyrazole Derivatives of Chalcone Scaffold. Research J. Pharm. and Tech. 2020; 13(1): 342-346.
40. Kulveer Singh, Suman Kumari, Y.K. Gupta. Synthesis and Antimicrobial Activity of New Pyrazoles and Chalcones Derived from Cyclic Imides. Research J. Pharm. and Tech 2017; 10(12): 4483-4488.
41. Babli Khatun, Venkatesh Kamath, Muddukrishna B. S., Aravinda Pai. Synthesis, Characterization and Anticancer Evaluation of Novel Analogues of Pyrazoles. Research J. Pharm. and Tech. 2021;14(4):2162-6.
42. Bhaskar S. Dawane, Baseer M Shaikh, Namdev T. Khandare, Gajanan G. Mandawad, Santosh S .Chobe, Shankaraiah G. Konda. Synthesis of Some Novel Substituted Pyrazole Based Chalcones and Their In-Vitro Antimicrobial Activity. Asian J. Research Chem. 3(1): Jan.-Mar. 2010; Page 90-93.
43. Kalpana Divekar, Shivakumar Swamy, Kavitha N., V. Murugan, Manish Devgun. Synthesis and Evaluation of Some New Pyrazole Derivatives as Antimicrobial Agents. Research J. Pharm. and Tech.3 (4): Oct.-Dec.2010; Page 1039-1043.
44. Yadav A.K., Mazhar Mehdi, Tasneem Fatima. Synthesis, Characterization and AntimicrobialActivity of Some new 1,4 Diaryl-3-Methyl-6-Imino-4,7-Dihydro-1,3-Thiazino (5,4-d) Pyrazoles. Asian J. Research Chem. 2018; 11(2):217-220.
45. Panneer Selvam T., Saravanan G., Prakash C. R., Dinesh Kumar P.. Microwave-Assisted Synthesis, Characterization and Biological Activity of Novel Pyrazole Derivatives. Asian J. Pharm. Res. 1(4): Oct. - Dec. 2011; Page 126-129.
46. Deepthi D. Kodical, Jainey P. James, Deepthi K, Pankaj Kumar, Chinchumol Cyriac, Gopika K.V. ADMET, Molecular docking studies and binding energy calculations of Pyrimidine-2-Thiol Derivatives as Cox Inhibitors. Research J. Pharm. and Tech 2020; 13(9):4200-4206.
47. Habeela Jainab N., Mohan Maruga Raja M. K.. In Silico Molecular Docking Studies on the Chemical Constituents of Clerodendrum phlomidis for its Cytotoxic Potential against Breast Cancer Markers. Research J. Pharm. and Tech 2018; 11(4): 1612-1618.
48. Li J., Abel R., Zhu K., Cao Y., Zhao S., Friesner R.A. The VSGB 2.0 model: A next generation energy model for high resolution protein structure modelling. Proteins. 2011, 79:2794-2812.