SYNTHESIS AND ANTI-TRICHINELLA SPIRALIS ACTIVITY IN VITRO OF SOME NEW 1H-BENZIMIDAZOLES

Anichina K.; Mavrova A.; Vuchev D.; Kondeva-Burdina M.

Anichina K. PhD, University of Chemical Technology and Metallurgy, Department of Organic Synthesis and Fuels
Mavrova A. PhD, University of Chemical Technology and Metallurgy, Department of Organic Synthesis and Fuels
Vuchev D. MD, PhD , Medical University, Departmant of Infectious diseases, parasitology and tropical medicine
Kondeva-Burdina M. PhD , Medicinal University of Sofia, Department of Pharmacology, Pharmacotherapy and Toxicology, Laboratory of Drug metabolism and drug toxicity

Keywords: Benzimidazoles, Antitrichinellosis activity, Hepatotoxicity

Abstract

Novel derivatives of 1H-benzimidazole which combine into a single molecule two pharmacophores – the benzimidazole and piperazine rings possessing antihelmintic activity have been synthesized. Their structures were confirmed by IR, 1H NMR, 13C NMR and elemental analysis techniques.
The compounds exhibited remarkable effect on the viability of isolated Trichinella spiralis muscle larvae in in vitro model at a dose of 100 μg/ml after 24 h. The results obtained by the hepatotoxicity test showed that compound 4 had the lowest hepatotoxity.

References

Bruno Gottstein, Edoardo Pozio, and Karsten Nöckler. Epidemiology, Diagnosis, Treatment, and Control of Trichinellosis.// Clin. Microbiol. Rev.- 2009. V. 22(1).-P. 127–145

Fabrizio Bruschi, Jean Dupouy-Camet, Wanda Kociecka, Edoardo Pozio, Francisco Bolas- Fernandez. Opinion on the diagnosis and treatment of human trichinellosis.// Expert Opin. Pharmacother.-2002. V. 3(8).-P. 1117-1130

William. C. Campbell (Ed.), Trichinella and Trichinosis, Plenum Press, USA and London, UK.- 1983.-P. 340-355

E. Pozio, D. Sacchini, L. Sacchi, A. Tamburrini, F. Alberici. Failure of Mebendazole in the Treatment of Humans with Trichinella spiralis Infection at the Stage of Encapsulating Larvae.// Clin. Infect. Dis.- 2001. V. 32.-P. 638-642

Anelia Ts. Mavrova, Kamelya K. Anichina, Dimitar I. Vuchev, Jordan A. Tsenov, Magdalena S. Kondeva, Mitka K. Micheva. Synthesis and antitrichinellosis activity of some 2- substituted-[1,3] thiazolo[3,2-a] benzimidazol-3 (2H)-ones.// Bioorg. and Med. Chem. -2005. V. 13. -P. 5550-5559

Anelia Ts. Mavrova, Kamelya K. Anichina, Dimitar I. Vuchev, Jordan A. Tsenov, Pavletta S. Denkova, Magdalena S. Kondeva, Mitka K. Micheva. Antihelminthic activity of some newly synthesized 5(6)-(un)substituted-1H-benzimidazol-2-ylthioacetylpiperazine derivatives. Eur. J. Med.Chem.// 2006. V. 41(12).-P. 1412-1420

Sat Narayan, Vinod Kumar, H. K. Pujary, Heterocyclic Systems Containing Bridgehead Nitrogen Atom: Part LII – Synthesis of 6,7-Dimethoxy & 5,8-Dimethoxy Thiazolo[3,2- a] benzimidazole-3 (2H)-ones, Thiazolo[3,2-a] benzimidazoles & 2,3- Dihydrothiazolo [3,2- a] benzimidazoles. Indian J. Chem.// 1986. V. 25B.-P. 267-270

A. V. Eltzov, K. M. Krivozheiko. Zh. Org. Khim.// 1966. V. 2.-P. 189, Russian

William. C. W. S. Campbell, in: R. Rew (Ed.), Chemotherapy of Parasitic Diseases, Plenum Press, New York. 1986.-P. 655

Fau D., Berson A., Eugene D., Fromenty B., Fisch C., Pessayre D. Mechanism for the hepatotoxicity of the antiandrogen nilutamide. Evidence suggesting that redox cycling of this nitroaromatic drug leads to oxidative stress in isolated hepatocytes. J Pharmacol Exp Ther.// 1992. V. 263.-P. 69-77

Mitcheva M, Kondeva M, Vitcheva V, Nedialkov P, Kitanov G. Effect of benzophenones from Hypericum annulatum on carbon tetrachloride – induced toxicity in fresh isolated rat hepatocytes. Redox Report.// 2006. V. 11(1).-P. 3-8