Adequate treatment of Parkinson’s disease is an important medical issue. Patients are suffered from numerous side effects of the widely used drugs. It has been found recently that monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl) cyclohex-3-ene-1,2-diol and its diacetate demonstrate high antiparkinsonian activity in some animal models. At the same time, their genetic safety was not studied yet. The aim of this research was to investigate the effect of these compounds with antiparkinsonian activities on reproduction of D. melanogaster. Over 4000 of fruitflies cultivated under the action of these compounds were analyzed. It was found that the chemicals did not provoke genetic mutations or alter reproduction of D. melanogaster. The possible explanations for the detected phenomena are provided. It was found that the compounds do not affect fertility in Drosophila..
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Ardashov OV, Zarubaev VV, Shtro AA, Korchagina DV, Volcho KP, Salakhutdinov NF, Kiselev OI. Antiviral activity of 3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol and its derivatives against influenza A(H1N1) 2009 virus. Lett Drug Des Discov 2011; 8: 375-80.
Il’ina IV; Volcho KP; Korchagina DV; Barkhash VA; Salakhutdinov N.F. Reactions of allyl alcohols of the pinane series and of their epoxides in the presence of montmorillonite clay. Helv Chim Acta 2007; 90: 353-68.
Malkov SV, Markelov VV, Polozov GY, Barabanschikov BI, Kozhevnikov AY, Trushin MV. Significant delay of lethal outcome in cancerpatients due to peroral administration of Bacillus oligonitrophilus KU-1. Scientific World J 2006; 6: 2177-87.
Malkov SV, Markelov VV, Polozov GY, Sobchuk LI, Zakharova NG, Barabanschikov BI, Kozhevnikov AY, Vaphin RA, Trushin MV Antitumor features of Bacillus oligonitrophilus KU-1 strain. J Microbiol Immunol Inf 2005; 38: 96-104.
Drinyaev VA, Mosin VA, Kruglyak EB, Novik TS, Sterlina TS, Ermakova NV, Kublik LN, Levitman MKh, Shaposhnikova VV, Korystov YN. Antitumor effect of avermectins. Eur J Pharmacol 2004; 501: 19-23.
Suresh S, Prithiviraj E, Venkata Lakshmi N, Karthik Ganesh M, Ganesh L, Prakash S. Effect of Mucuna pruriens (Linn.) on mitochondrial dysfunction and DNA damage in epididymal sperm of streptozotocin induced diabetic rat. J Ethnopharmacol 2013; 145: 32-41.
Bajguz A, Bąkała I, Talarek M. Ecdysteroids in plants and their pharmacological effects in vertebrates and humans. Stud Nat Prod Chem 2015; 45: 121-45.
David JR, Allemand R, Capy P, Chakir M, Gibert P, Pétavy G, Moreteau B. Comparative life histories and ecophysiology of Drosophila melanogaster and D. simulans. Genetica 2004; 120:151-63.
Siddall NA, Hime GR. A Drosophila toolkit for defining gene function in spermatogenesis. Reproduction 2017; 153: R121-R132.
Graf U, Abraham SK, Guzmán-Rincón J, Würgler FE. Antigenotoxicity studies in Drosophila melanogaster. Mut Res Fund Mol Mech Mut 1998; 402: 203-9.
Gürbüzel M, Çapoğlu İ, Kızılet H, Halıcı Z, Özçiçek F, Demirtaş L. Genotoxic evaluation of two oral antidiabetic agents in the Drosophila wing spot test. Toxicol Ind Health 2014; 30: 376-83.
Danesi CC, Dihl RR, Bellagamba BC, de Andrade HH, Cunha KS, Guimarães NN, Lehmann M. Genotoxicity testing of combined treatment with cisplatin, bleomycin, and 5-fluorouracil in somatic cells of Drosophila melanogaster. Mutation Res 2012; 747: 228-33.
Frei H, Clements J, Howe D, Würgler FE. The genotoxicity of the anti-cancer drug mitoxantrone in somatic and germ cells of Drosophila melanogaster. Mutat Res Genet Toxicol 1992; 279: 21-33.
Delgado-Rodríguez A, Ortíz-Marttelo R, Villalobos-Pietrini R, Gómez-Arroyo S, Graf U. Genotoxicity of organic extracts of airborne particles in somatic cells of Drosophila melanogaster. Chemosphere 1999; 39: 33-43.
Blandini F, Armentero M-T. Animal models of Parkinson’s disease. FEBS J 2012 279: 1156-66.
Vanhauwaert R, Verstreken P. Flies with Parkinson’s disease. Exp Neurol 2015; 274: 42-51.
Navarro JA, Heßner S, Yenisetti SC, Bayersdorfe F, Zhang L, Voigt A, Schneuwly S, Botella JA. Analysis of dopaminergic neuronal dysfunction in genetic and toxin-induced models of Parkinson’s disease in Drosophila. J Neurochem 2014; 131: 369-82.
Trushin MV, Ardashov OV, Volcho KP, Arkharova IA, Salakhutdinov NF. Genotoxicological safety assessment of a new antiparkinsonian substance ((1R,2R,6S)-3-methyl-6(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol). World J Med Sci 2013; 8: 355-8.
Salakhutdinov NF; Tolstikova TG; Pavlova AV; Morozova EA; Ilina IV; Ardashov OV; Volcho KP. Agent for treating Parkinson’s disease. Patent US 8809391, 2014.
Ardashov OV, Pavlova AV, Korchagina DV, Volcho KP, Tolstikova TG, Salakhutdinov NF. Antiparkinsonian activity of some 9-N-, O-, S- and C-derivatives of 3-methyl-6-(prop1-en-2-yl)cyclohex-3-ene-1,2-diol. Bioorg Med Chem 2013; 21: 1082-7.
Tolstikova TG, Pavlova AV, Morozova YA, Ardashov OV, Il’ina IV, Volcho KP, Salakhutdinov NF, Tolstikov GA. A highly effective antiparkinsonian drug of a new structural type. Dokl Biol Sci 2010; 435: 398-9.
Ardashov OV, Pavlova AV, Il’ina IV, Morozova EA, Korchagina DV, Karpova EV, Volcho KP, Tolstikova TG, Salakhutdinov NF. Highly potent activity of (1R,2R,6S)-3-methyl-6-(prop-1-en2-yl)cyclohex-3-ene-1,2-diol in animal models of Parkinson’s disease. J Med Chem 2011; 54: 3866-74.
Brogden RN, Speight TM, Avery GS. Levodopa: A review of its pharmacological properties and therapeutic uses with particular reference to parkinsonism. Drugs 1971; 2: 262-400.
Kakkar AK, Dahiya N. Management of Parkinson’s disease: Current and future pharmacotherapy. Eur J Pharmacol 2015; 750: 74-81.