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 IJOC  Vol.6 No.1 , March 2016
Synthesis, Molecular Structure and Anti-Onchocercal Studies of 1-(Phthalazin-1(2H)-one)[(Pyridin-2-yl)ethylidene]hydrazone
Abstract: The novel ligand, 1-(phthalazin-1(2H)-one)[(pyridin-2-yl)ethylidene]hydrazone,(APN), derived from the antihypertensive drug, hydralazine hydrochloride, was synthesized and characterized by spectroscopic methods (IR, 1H NMR). The X-ray crystallographic data indicates that APN has an exocyclic C=N bond on the hydralazine moiety. APN revealed significant anti-onchocercal activity with IC50 values of 0.3125 μg/mL on microfilaria and 10 μg/mL on adult worms compared to the standard drug, ivermectin.
Cite this paper: Yong, J. , Majoumo-Mbe, F. , Samje, M. and Nfor, E. (2016) Synthesis, Molecular Structure and Anti-Onchocercal Studies of 1-(Phthalazin-1(2H)-one)[(Pyridin-2-yl)ethylidene]hydrazone. International Journal of Organic Chemistry, 6, 77-84. doi: 10.4236/ijoc.2016.61008.
References

[1]   Nfor E.N., Husian, A., Majoumo-Mbe, F., Njah, N.N., Offiong, E.O. and Bourne, S.A. (2013) Synthesis, Crystal structure and Antifungal Activity of Ni(II) Complex of a New Hydrazine Derived from Antihypertensive Drug Hydralazine Hydro-chloride. Polyhedron, 63, 217-213.
http://dx.doi.org/10.1016/j.poly.2013.07.028

[2]   Sultana, N., Sarfaraz, T.B., Nelofar, A. and Hussain, S.A. (2007) Potential Antibacterial Agents: Part VI—Synthesis and Structure Elucidation of Schiff Bases Derived from Hydralazine. Pakistan Journal of Scientific and Industrial Research, 50, 169-172.

[3]   El-Sherif, A.A., Shoukry, M.M. and Abd-Elgawad, M.M. (2012) Synthesis, Characterization, Biological Activity and Equilibrium Studies of Metal(II) Ion Complexes with Tridentate Hydrazine Ligand Derived from Hydralazine. Spectrochemica Acta Part A Molecular and Biomolecular Spectroscopy, 98, 307-321.
http://dx.doi.org/10.1016/j.saa.2012.08.034

[4]   Bakale, R.P., Naik, G.N., Mangannavar, C.V., Muchchandi, I.S., Shcherbakov, I.N., Frampton, C. and Gudasi, K.B. (2014) Mixed Ligand Complex via Zinc(II)-Mediated in Situ Oxidative Heterocyclization of Hydrochloride Salt of 2-Chlorobenzaldehyde Hydral-azine Hydrazone as Potential of Antihypertensive Agent. European Journal Medicinal Chemistry, 12, 38-45.
http://dx.doi.org/10.1016/j.ejmech.2013.11.037

[5]   Bouguerne, B., Belkheiri, N., Bedos-Belval, F., Vindis, C., Uchida, K., Duran, H., Grazide, M.H., Baltas, M., Salvayre, R. and Nègre-Salvayre, A. (2011) Antiatherogenic Effect of Bisvanillyl-Hydrazone, a New Hydralazine Derivative with Antioxidant, Carbonyl Scavenger, and Antiapoptotic Properties. Antioxidant and Redox Signaling, 14, 2093-2106.
http://dx.doi.org/10.1089/ars.2010.3321

[6]   Burton-Pye, B.P., Heath, S.L. and Faulker, S. (2005) Synthesis and Luminescence Properties of Lanthanide Complexes Incorporating a Hydralazine-Derived Chromophore. Dalton Transactions, 7, 146-149.
http://dx.doi.org/10.1039/b413005g

[7]   Rollas, S. and Kücükgüzel, S.G. (2007) Biological Activities of Hydrazone Derivatives. Molecules, 12, 1910-1939.
http://dx.doi.org/10.3390/12081910

[8]   Sah, P.P.T. and Peoples, S.A. (1954) Isonicotinyl Hydrazones as Antitubercular Agents and Derivatives for Identification of Aldehydes and Ketones. Journal of American Pharmaceutical Association, 43, 513-524.
http://dx.doi.org/10.1002/jps.3030430902

[9]   WHO Onchocerciasis: Fact Sheet No. 374, Updated March, 2015.
http://www.who.int/mediacentre/factsheets/fs374/en/

[10]   Lustigman, S. and McCarter, J.P. (2007) Ivermectin Resistance in Onchocerca volvulus: Toward a Genetic Basis. PLoS Neglected Tropical Disease, 1, e76.
http://dx.doi.org/10.1371/journal.pntd.0000076

[11]   Osei-Atweneboana, M.Y., Eng, J.K., Boakye, D.A., Gyapong, J.O. and Prichard, R.K. (2007) Prevalence and Intensity of Onchocerca volvulus Infection and Efficacy of Ivermectin in Endemic Communities in Ghana: A Two-Phase Epidemiological Study. Lancet, 369, 2021-2029.
http://dx.doi.org/10.1016/S0140-6736(07)60942-8

[12]   CrysAlis Pro: Data Collection and Data Reduction Software Package. Agilent Technologies.
http://www.selectscience.net/products/crysalispro/?prodID=197116

[13]   CrysAlis RED, Oxford Diffraction Ltd., Version 1.171.35.11 (2011).

[14]   SHELX Includes SHELXS97, SHELXL97: Sheldrick, G.M. (2008) A Short History of SHELX. Acta Crystallographica A, 64, 112-122.
http://dx.doi.org/10.1107/S0108767307043930

[15]   Farrugia, L.J. (1997) ORTEP-3 for Windows—A Version of ORTEP III with a Graphical User Interface (GUI). Journal Applied Crystallography, 30, 565.
http://dx.doi.org/10.1107/S0021889897003117

[16]   . Macrae, C.F., Bruno, I.J., Chisholm, J.A., Edgington, P.R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. and Wood, P.A. (2008) Mercury CSD 2.0—New Features for the Visualization and Investigation of Crystal Structures. Journal Applied Crystallography, 41, 466-470.
http://dx.doi.org/10.1107/S0021889807067908

[17]   Cho-Ngwa, F., Abongwa, M., Ngemenya, M.N. and Nyongbela, K.D. (2010) Selective Activity of Extracts of Margaritaria discoidea and Homalium africanum on Onchocerca ochengi. BMC Complementary and Alternative Medicine, 10, 62. http://dx.doi.org/10.1186/1472-6882-10-62

[18]   Samje, M., Metuge, J.A., Mbah, J.A., Nguesson, B. and Cho-Ngwa, F. (2014) In Vitro Anti-Onchocercaochengi Activities of Extracts and Chromatographic Fractions of Craterispermum laurinum and Morindalucida. BMC Complementary and Alternative Medicine, 14, 325.
http://dx.doi.org/10.1186/1472-6882-14-325

[19]   Bulman, C.A., Bidlow, C.M., Lustigman, S., Cho-Ngwa, F., Williams, D., Rascón Jr., A.A., Tricoche, N., Samje, M., Bell, A., Suzuki, B., Lim, K.C., Supakorndej, N., Supakorndej, P., Wolfe, A.R., Knudsen G. M., Chen, S., Wilson, C., Ang, K-H., Arkin, M., Gut, J., Franklin, C., Marcellino, C., McKerrow, J.H., Debnath, A. and Sakanari, J.A. (2015) Repurposing Auranofin as a Lead Candidate for Treatment of Lymphatic Filariasis and Onchocerciasis. PLoS Neglected Tropical Disease, 9, e0003534.
http://dx.doi.org/10.1371/journal.pntd.0003534

[20]   Majoumo-Mbe, F., Nfor, E.N., Sengeh, E.B., Njong, R.N. and Offiong, E.O. (2015) Synthesis, Crystal Structure and Biological Activity of 1-(Phthalazin-1(2H)-one)[(Pyridin-2-yl)ethylidene]hydrazine. Communications in Inorganic Synthesis, 3, 40-46.

[21]   Kogan, V.A., Levchenkov, S.I., Popov, I.D. and Sherherbakov, L.A. (2009) 1-Hyralazinophthalazine-Based Hydrazones and Their Transition Metal Complexes: Structure and Biological Activity. Russian Journal of General Chemistry, 79, 2767-2775.
http://dx.doi.org/10.1134/S1070363209120354

[22]   Awadzi, K., Attah, S.K., Addy, E.T., Opoku, N.O. and Quartey, B.T. (2004) Thirty Month Follow-Up of Sub-Optimal Responders to Multiple Treatments with Ivermectin, in Two Onchocerciasis-Endemic Foci in Ghana. Annals of Tropical Medicine and Parasitology, 98, 359-370.
http://dx.doi.org/10.1179/000349804225003442

 
 
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