Synthesis and biological evaluation of a novel series of aryl S,N-ketene acetals as antileishmanial agents

Bioorganic and Medicinal Chemistry Letters

Volumn 23, Issue 13, 2013, Pages 3979-3982

  Suryawanshi, S N ^a   Kumar, Santosh ^a   Tiwari, Avinash ^a   Shivahare, Rahul ^a   Chhonker, Yashpal Singh ^a   Pandey, Susmita ^a   Shakya, Nishi ^a   Bhatta, Rabi Sankar ^a   Gupta, Suman ^a  

^a CENTRAL DRUG RESEARCH INSTITUTE   (India)

Author keywords

Antileishmanial activity; Aryl S,N ketene acetal; Hamster; Leishmania donovani; Pharmacokinetic studies

Indexed keywords

3,4,5 TRIMETHOXY ARYL S,N KETENE ACETAL DERIVATIVE; ACETAL; ANTILEISHMANIAL AGENT; KETENE DERIVATIVE; PAROMOMYCIN; STIBOGLUCONATE SODIUM; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIPROTOZOAL ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG CLEARANCE; DRUG METABOLISM; DRUG SCREENING; DRUG SELECTIVITY; DRUG SYNTHESIS; IC 50; IN VITRO STUDY; IN VIVO STUDY; LEISHMANIA DONOVANI; LEISHMANIASIS; LIVER MICROSOME; NONHUMAN;

ACETALS; ANTIPARASITIC AGENTS; DOSE-RESPONSE RELATIONSHIP, DRUG; ETHYLENES; KETONES; LEISHMANIA DONOVANI; MOLECULAR STRUCTURE; PARASITIC SENSITIVITY TESTS; STRUCTURE-ACTIVITY RELATIONSHIP;

CRICETINAE; LEISHMANIA DONOVANI;

EID: 84878833772     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2013.04.025     Document Type: Article

References (30)

1. F. Chappuis, S. Sundar, A. Hailu, H. Ghalib, S. Rijal, R.W. Peeling, J. Alvar, and M. Boelaert Nat. Rev. Microbiol. 5 2007 873
2. U. Sharma, and S.J. Singh Vector Borne Dis. 45 2008 255
3. S. Gupta, and S. Nishi Indian J. Med. Res. 133 2011 27
4. L.V. Alves, M.M. Do Canto-Cavalheiro, L. Cysne-Finkelstein, and L. Leon Biol. Pharm. Bull. 26 2003 453
5. T. Koide, M. Nose, Y. Ogihara, Y. Yabu, and N. Ohta Biol. Pharma. Bull. 25 2002 131
6. D.C. Gomes, L.V. de Alegrio, M.E. Freire de Lima, L.L. Leon, and C.A. Araujo Arzneim.-Farsch. Drug Res. 52 2002 120
7. N. Tan, M. Kaloga, O.A. Radtke, A.F. Kiderlen, S. Oksuz, A. Ulubelen, and H. Kolodziej Phyto-chemistry 61 2002 881
8. M. Sairafianpour, J. Christensen, D. Staerk, B.A. Budnik, A. Kharazmi, K. Bagherzadeh, and J.W. Jaroszewski J. Nat. Prod. 64 2001 1398
9. A.J. Valderrama, J. Benites, M. Cortes, H. Pessoa-Mahana, E. Prina, and A. Fournet Bioorg. Med. Chem. 11 2003 4713
10. M. Liu, P. Wilairat, S.L. Croft, A.L.C. Tan, and M.L. Go Bioorg. Med. Chem. 11 2003 2729
11. S.F. Chowdhury, R. Di Lucrezia, R.H. Guerrero, R. Brun, J. Goodman, L.M. Ruiz-Perez, D.G. Pacanowska, and I.H. Gilbert Bioorg. Med. Chem. Lett. 11 2001 977
12. S.F. Chowdhury, V.B. Villamor, R.H. Guerrero, I. Leal, R. Brun, S.L. Croft, J.M. Goodman, L. Maes, L.M. Ruiz-Perez, D.G. Pacanowska, and I.H. Gilbert J. Med. Chem. 42 1999 4300
13. A. Foroumadi, S. Emami, M. Sorkhi, M. Nikhjiri, Z. Nazarian, S. Heydari, S.K. Ardestani, F. Poorrajab, and A. Shafiee Chem. Biol. Drug Des. 75 2010 590
14. D. Saleheen, S.A. Ali, K. Ashfaq, A.A. Siddiqui, A. Agha, and M.M. Yasinzai Biol. Pharm. Bull. 25 2002 386
15. H. Ohtsu, H. Itokawa, Z. Xiao, C.Y. Su, C.C.Y. Shih, T. Chiang, E. Chang, Y.F. Lee, S.Y. Chiu, C. Chang, and K.H. Lee Bioorg. Med. Chem. 11 2003 5083
16. D.C. Ferriera de Gomez, L.V. Alegrio, L.L. Leon, and F. de Lima Arzneim.-Forsch. Drug Res. 52 2002 695
17. R.I. Tsukiyama, H. Katsura, N. Tokuriki, and M. Kobayashi Antimicrob. Agents Chemother. 46 2002 1226
18. M. Chen, L. Zhai, S.B. Christensen, T.G. Theander, and A. Kharazmi Antimicrob. Agents Chemother. 45 2001 2023
19. B.S. Patro, S. Rele, G.J. Chintalwar, S. Chattopadhyay, S. Adhikari, and T. Mukherjee ChemBioChem 3 2002 364
20. S. Pandey, S.N. Suryawanshi, S. Gupta, and V.M.L. Srivastava Eur. J. Med. Chem. 39 2004 969
21. J.R. Suresh, U.K.S. Kumar, H. Ila, and H. Junjappa Tetrahedron 57 2001 781
22. S. Kumar, A. Tiwari, S.N. Suryawanshi, M. Mittal, P. Vishwakarma, and S. Gupta Bioorg. Med. Chem. Lett. 22 2012 6728
23. A. Kumar, V. Aggarwal, H. Ila, and H. Junjappa Synthesis 1980 748
24. Y. Dong, M. Wang, J. Liu, W. Ma, and L. Qun Chem. Commun. 47 2011 7380
25. S. Pandey, S.N. Suryawanshi, S. Gupta, and V.M.L. Srivastava Eur. J. Med. Chem. 40 2005 751
26. J.J. Bogaards, M. Bertrand, P. Jackson, M.J. Oudshoorn, R.J. Weaver, P.J. van Bladeren, and B. Walther Xenobiotica 30 2000 1131
27. 2 incubator for 72 h. After incubation, the compound-containing medium was aspirated and 50 μL PBS was added in each well and mixed with an equal volume of steady Glo® reagent. After gentle shaking for 1-2 min, the reading was taken in a luminometer (Pandey et al., 2007). The inhibition of parasitic growth was determined as described above. S. Pandey, S.N. Suryawanshi, S. Nishi, N. Goyal, and S. Gupta Eur. J. Med. Chem. 42 2007 669
28. 50) values were estimated as described by Huber and Koella (1993). T. Mosmann J. Immunol. Methods 65 1983 55
29. W. Huber, and J.C. Koella Acta Trop. 55 1993 257
30. In vivo antileishmanial assay: the in vivo antileishmanial activity was carried out in golden hamsters infected with L. donovani as described by Kumar et al. (2012). Briefly, golden hamsters (inbred strain) of either sex weighing 40-45 g were infected intracardiacally with 1 × 107 amastigotes per animal. After establishment of infection, drug treatment (50 mg/kg) by either (intraperitoneal) ip or per oral (po) route was initiated for five consecutive days. Sodium stibogluconate (SSG) and paromomycin are used as reference drugs. Post-treatment biopsies were done on day 7 after the last drug administration and amastigote counts are assessed by Giemsa staining. Intensity of infection in both, treated and untreated animals, and also the initial count in treated animals was compared and the efficacy was expressed in terms of percent inhibition (PI). S. Kumar, A. Tiwari, S.N. Suryawanshi, M. Mittal, P. Vishwakarma, and S. Gupta Bioorg. Med. Chem. Lett. 22 2012 6728