Journal of
Microbiology and Antimicrobials

  • Abbreviation: J. Microbiol. Antimicrob.
  • Language: English
  • ISSN: 2141-2308
  • DOI: 10.5897/JMA
  • Start Year: 2009
  • Published Articles: 160

Full Length Research Paper

Searching for new antileishmanial lead drug candidates: Synthesis, biological and theoretical evaluations of promising thieno[2,3-b]pyridine derivatives

Luiz C. S. Pinheiro1, Rodrigo Tonioni2,3, Plínio C. Sathler2, Helena C. Castro 2,3,4,*, Alice M. R. Bernardino1, Uiaran O. Magalhães5, Lúcio Cabral5, Carlos R. Rodrigues5, Júlio C. Borges1, Maurício S. dos Santos1, Vitor F. Ferreira1, Samara N. Braga4, Saulo C. Bourguignon4, and Dilvani O. Santos3* 
  1Programa de Pós-Graduação em Química - IQ, Universidade Federal Fluminense, CEP 24020-150, Niterói-RJ, Brazil. 2Programa de Pós-Graduação em Patologia - HUAP, Universidade Federal Fluminense,  CEP 24020-150, Niterói-RJ, Brazil. 3LaBiopAc and LABioMol, Universidade Federal Fluminense, CEP 24020-150, Niterói-RJ, Brazil. 4Programa de Pós-Graduação em Biologia das Interações – IB, Universidade Federal Fluminense, CEP 24020-150, Niterói-RJ, Brazil. 5Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, ModMolQSAR, CEP 21941-590, Rio de Janeiro, Brazil.
Email: [email protected]

  •  Accepted: 14 November 2011
  •  Published: 31 January 2012

Abstract

 

Cutaneous leishmaniasis is a parasitic disease associated with high morbidity and mortality rates. This work reports the synthesis, biological and theoretical evaluations of a new antileishmanial series of 5-(4,5-dihydro-1H-imidazol-2-yl)-4-(arylamino)thieno[2,3-b]pyridine derivatives - 3 (H),  3a (m-CH3), 3b (m-OCH3), 3c (m-NO2), 3d (m-F), 3e (m-Br), 3f (p-CH3), 3g (p-OCH3), 3h (p-NO2), 3i (p-F), 3j (p-Br). Interestingly 3f and 3g showed a better profile against Leishmania amazonensis (EC50=29.49 and 32.23 μM, respectively) than glucantime, the current drug on the market (EC50=163.7 μM). The theoretical analysis pointed a correlation among the antileishmanial profile and the conformational and electrostatic features of these new molecules. ADMET and “Lipinski´s rule of 5” revealed higher theoretical biodisponibility, druglikeness and drugscore values for these derivatives compared to known antileishmanial drugs. Our results pointed these thieno[2,3-b]pyridine derivatives as lead compounds for designing new agents for treatment of cutaneous leishmaniasis.

 

Key words: Cutaneous leishmaniasis, antileishmanial, thieno[2,3-b]pyridine derivatives, structure-activity relationship (SAR)