Antiviral Activity Of Adamantane-Pyrazole Derivatives Against Foot And Mouth Disease Virus Infection In Vivo And In Vitro With Molecular Docking Study | ||
| Journal of Applied Veterinary Sciences | ||
| Article 5, Volume 5, Issue 4, October 2020, Pages 37-46 PDF (1.19 M) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/javs.2020.118001 | ||
| Authors | ||
| Mohammed M. S. Wassel1; Wael M. Gamal Eldin* 1; Ahmed Ragab2; Gameel A. M. Elhag Ali2; Yousry A. Ammar2 | ||
| 1Department of Foot and Mouth Disease, Veterinary Serum and Vaccine Research Institute (VSVRI), Agricultural Research Center (ARC), Abbasia, Cairo, Egypt. | ||
| 2Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City, 11884, Cairo, Egypt. | ||
| Abstract | ||
| Foot-and-mouth disease (FMD) vaccine does not afford early effective protection until adaptive immune protection caused by the vaccination occurs. Therefore, an alternative prophylactic application of antiviral agents for inhibition of the FMD virus is needed, and this is the scope of this study. In this study, we tested nine adamantane-pyrazole derivatives that could exhibit antiviral activity against FMDV infection either in vitro through baby hamster kidney cells (BHK-21 cells) infected with FMD virus serotypes O pan Asia. Cytotoxicity Concentration 50 (CC50) activity of pyrazole derivatives (1, 2, 3, 4, 5a,b, 6a-c) were detected on BHK-21 cells and ranged between 500 to 3000µg/ml. Inhibitory Concentration 50 (IC50) on BHK-21 was achieved only for the most promising three derivatives 6a-c and exhibited an antiviral activity with a therapeutic index of 30, and that was reflected on the antiviral activity response in baby mice with different concentrations where a concentration of 50 µg/ml for pyrazole derivatives 6a and 6c compounds and 40 µg/ml for bis-tolyl pyrazole 6b that achieve 100% protection and this results was as effective as 50 µg/ml of amantadine. Specifically, diaryl pyrazole derivatives 6a-c that protected for six days following FMDV challenge. These results suggested that pyrazole derivatives 6a-c could be used as an effective antiviral agent against FMD virus infection. Molecular docking simulation of the target compounds 6a-c had good binding energy and the tested compounds recommended being an excellent 3C protease inhibitor compared to Amantadine and Ribavirin. These findings may explain the antiviral activity of the target compounds. | ||
| Keywords | ||
| Adamantane derivatives; Amantadine; Antiviral; BHK-21 cells; FMDV | ||
| References | ||
|
AO. D., GUO. H-C., SUN. S-Q., SUN. D-H., FUNG. TS., WEI. Y-Q. 2015. Viroporin Activity of the Foot-and-Mouth Disease Virus Non-Structural 2B Protein. PLoSONE, 10(5): e0125828.
AGGOUR. A. MA. 2006. The effect of amantadine as antiviral on foot and mouth virus replication, Zag. Vet. J. vol.34, NO.2, page.103-108.
AGNEW-FRANCISA. K. A. AND WILLIAMS. C. M., SYNTH.CATAL. ADV. 2016. Catalysts Containing the Adamantane Scaffold, advanced synthesis and catalysis review, 358, 675-700.
AUGERI. D. J., ROBL. J. A., KIM. SM., PARK. J.H., LEE. KN., KIM.SK., YJ KO., LEE. IS. 2012. Enhanced inhibition of foot-and-mouth disease virus by combinations of porcine interferon-alpha and antiviral agents. Antivir. Res., 96, 213-220.
BOREKO. E. I., KLIMOCHKIN. YU. N., SHIRYAEV. A. K. 2007. Progress in Adamantane Chemistry [in Russian], Khimiya, Moscos, pp. 70-88.
DIAZ-SAN. SF., MEDINA. GN., STENFELDT. C., ET AL., 2017. Foot-and-mouth disease vaccines, Vet. Microbiol. 206,102-112.
EL-SHARIEF. AMS., AMMAR. Y. A., BELAL. A., EL-SHARIEF. MAS., MOHAMED. Y. A., MEHANY. A.B. and RAGAB. A., 2019. Design, synthesis, molecular docking and biological activity evaluation of some novel indole derivatives as potent anticancer active agents and apoptosis inducers. Bioorganic Chemistry, 85, 399-412.
FUKUDA.T., UMEKI. T., TOKUSHIMA. K., XIANG. G., YOSHIDA. Y., ISHIBASHI, F., IWAO. M.,2017. Design, synthesis, and evaluation of A-ring-modified lamellar in N analogues as noncovalent inhibitors of the EGFR T790M/L858R mutant. Bioorganic & medicinal chemistry,25(24), 6563-580.
FDA., 2006. Guidance for industry antiviral product development –conducting and submitting virology studies to the agency.
GRUBMAN. MJ and BAXT. B., 2004. Foot-and-mouth disease, Clinical Microbiology. Reveiw. 17, 465-493.
GLADUE. DP., HOLINKA. LG., LARGO. E., FERNANDEZ. S. I., CARRILLO. C., O'DONNELL. V., 2012. Classical swine fever virus p7 protein is a viroporin involved in virulence in swine. Journal of virology. 86(12):6778-91.
HASSAN. A. S., ASKAR. A. A., NAGLAH. A. M., ALMEHIZIA. A. A., AND A. RAGAB,2020. Discovery of New Schiff Bases Tethered Pyrazole Moiety: Design, Synthesis, Biological Evaluation, and Molecular Docking Study as Dual Targeting DHFR/DNA Gyrase Inhibitors with Immuno-modulatory Activity. Molecules, 25(11), 2593.
IBRAHIM. E. E., EL-HELW. H.A., SHAFIK. N.G. AND MEKHAIL. M. A., 2017. Conjugation of Foot And Mouth Disease IgY In Chicken Egg Yolk With Horse Radish Peroxidase For Typing of Foot And Mouth Disease Virus. Journal of Applied Veterinary Sciences,2(1): 35-42. IGUMNOVA. N. D., LEMINA. E., BITIUKOVA. I. I., KLIMOVA. N. V. AND SKOLDINOV. A. P., FARMAKOL. T., 1988. Hydrolysis by plasma cholinesterase of complex adamantyl-containing esters. Farmakol Toksikol,51, 38–41.
INTHARATHEP. P., LAOHPONGSPAISAN. C., RUNGROTMONGKOL. T., LOISRUANGSIN. A., MALAISREE. M., DECHA. P., 2008. How amantadine and rimantadine inhibit proton transport in the M2 protein channel. Journal of molecular graphics & modelling. 27(3):342-8.
JENSEN. L. S., BOLCHO. U., EGEBJERG. J.,2006.Drugs Targeting Protein–Protein Interactions .Chem. Med. Chem., 1(4), 419-428.
KAZIMIERCZUK. Z., GORSKA. A., SWITAJ. T., AND LASEK. W., 2001. Adamantyl amino pyrimidines and -pyridines are potent inducers of tumor necrosis factor-alpha. Bioorg. Med. Chem. Lett., 11, 1197–1200.
KITAGAWA. K., MIZOBUCHI. N., HAMA. T., HIBI. T., KONISHI. R. AND FUTAKI. S.,1997. Synthesis and Antinociceptive Activity of [D-Ala2]Leu-Enkephalin Derivatives Conjugated with the Adamantane Moiety. Chem. Pharm. Bull., 45, 1782–1787.
LONG. J., MANCHANDIA. T., BAN. K., 2007. Adaphostin cytoxicity in glioblastoma cells is ROS-dependent and is accompanied by up regulation of heme oxygenase-1.Cancer Chemother. Pharmacol, 59, 527-535.
LU. D., MENG. Z., THAKUR G. A., 2005. Adamantyl Cannabinoids: A Novel Class of Cannabinergic Ligands .J. Med. Chem., 48(14), 4576-4585.
MAURO. P., MORAES. K., TERESA. S., MARLA. D., TRACI. S., HE. W., VLADIMIR. G., AND MARVIN. J. G.,2007. Enhanced Antiviral Activity against Foot-and-Mouth Disease Virus by a Combination of Type I and II Porcine Interferons, J. of virology, p. 7124-7135.
MOTORNAYA. A. E., ALIMBAROVA. L. M., SHOKOVA. E. A., 2006. Synthesis and antiherpetic activity of N-(3-amino-1-adamantyl)calix[4]arenes. Pharm. Chem. J., 40(2), 68-72.
MORAES. MP, DE LOS. S.T., KOSTER. M., et al.,2007. Enhanced antiviral activity against foot and-mouth disease virus by a combination of type I and II porcine interferons, J. Virol., 81, 7124-7135.
MOREL-DESROSIERS. N., AND MOREL. J. P.,1979. Standard molar enthalpies, volumes, and heat capacities of adamantane in cyclohexane,n-hexane, and carbon tetrachloride. Interpretation using the scaled-particle theory .J. Solution Chem., 8, 579-592.
MOISEEV I. K., KON’KOV. S. A .,OVCHINNIKOV. K. A., 2012.Synthesis and antiviral activity of new adamantane derivatives.Pharmaceutical Chemistry Journal vol.45, pages588–592.
NAYYAR. A., MONGA. V., MALDE. A., 2007. Synthesis, anti-tuberculosis activity, and 3D-QSAR study of 4-(adamantan-1-yl)-2-substituted quinolines .Bioorg. Med. Chem., 15(2), 626-640.
PINTO. LH., LAMB. RA.,2007. Controlling influenza virus replication by inhibiting its proton channel. Molecular bioSystems. 3(1):18-23.
PREMKUMAR. A., DONG. X., HAQSHENAS. G., GAGE. PW., GOWANS. EJ.,2006. Amantadine inhibits the function of an ion channel encoded by GB virus B, but fails to inhibit virus replication. Antiviral therapy.,11(3):289–95.
REED. LJ, MUENCH. H.,1938. A simple method for estimating fifty percentage end point. Am. J. Hyg.,27:493-497.
SALEM. M. A., RAGAB. A., EL-KHALAFAWY. A., MAKHLOUF. A. H., ASKAR. A. A. and AMMAR. Y. A., 2020. Design, synthesis, in vitro antimicrobial evaluation and molecular docking studies of indol-2-one tagged with morpholinosulfonyl moiety as DNA gyrase inhibitors. Bioorganic Chemistry, 96, 103619.
SCHLESINGER. F., TAMMENA. D., KRAMPFL. K., AND BUFLER. J., BR 2005. Two mechanisms of action of the adamantane derivative IEM-1460 at human AMPA-type glutamate receptors. J. Pharmacol., 145(5), 656-663.
SARKAR S., RAMASAMY. P. T. S., VEERAKYATHAPPA. B.,2019. In vitro antiviral efficacy of pleconaril and Ribavirin on foot-and-mouth disease virus replication. Virus. Dis. 30(4):562-570.
SINGH.C., KANCHAN.R., SHARMA. U., AND S. PURI.K., 2007. New Adamantane-Based Spiro 1,2,4-Trioxanes Orally Effective against Rodent and Simian Malaria. J. Med. Chem., 50(3), 521-527.
SOUDY. A.F., 2019. Prophylactic control of mycoplasma contamination in starting biological materials used in viral vaccine production, Journal of Applied Veterinary Sciences, 4(1): 30-34.
STEINMANN. E., WHITFIELD. T., KALLIS. S., DWEK. RA., ZITZMANN. N., PIETSCHMANN. T., 2007. Antiviral effects of amantadine and iminosugar derivatives against hepatitis C virus. Hepatology. 46(2):330-8.
STROBER. W., 2011. Trypan blue exclusion test of cell viability. Curr Protocol Immunol. 111:A3.B.1-A3.B.3, 1-2.
VILLHAUER. E. B., BRINKMAN. J. A., NADERI. G. B., 2003. 1-[[(3-Hydroxy-1-damantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: A Potent, Selective, and Orally Bioavailable Dipeptidyl Peptidase IV Inhibitor with Antihyperglycemic Properties.J. Med. Chem., 46(13), 2774-2789.
WASSEL. M.M.S., RAGAB. A., ELHAG ALI. G.A.M., MEHANY. A. B. M. and AMMAR. Y. A., ,2020. Novel adamantane-pyrazole and hydrazone hybridized: design, synthesis, cytotoxic evaluation, SAR study and molecular docking simulation as carbonic anhydrase inhibitors. Journal of Molecular Structure, 1223,128966.
WHITE. DO. AND FENNER. FJ., 1984. Antiviral chemotherapy, interferons and vaccines. ,Monographs in Virology.pp. 36–48.
XUAN. H., LI. Y., FANG. H., ANDZHENG. C., 2011.Establishement of persistent infection with foot and mouth disease virus in BHK-21cells.virol. J.,8:169.
YU. Z., SAWKAR. A. R., WHALEN. L. J., 2007. Isofagomine- and 2, 5-anhydro-2, 5-imino-D-glucitol-based glucocerebrosidase pharmacological chaperones for Gaucher disease intervention. J. Med. Chem., 50(1), 94-100.
ZHANG. Z. D., HUTCHING. G., KITCHING. P., AND ALEXANDERSEN. S., 2002. The effects of gamma interferon on replication of foot-and-mouth disease virus in persistently infected bovine cells. Arch. Virol. 147:2157–2167 | ||
|
Statistics Article View: 902 PDF Download: 968 |
||
