title: Synthesis and activity of novel homodimers of Morita-Baylis-Hillman adducts against Leishmania donovani: A twin drug approach.
abstract: It is reported here the synthesis of novel Homodimers 12-19 of Morita-Baylis-Hillman adducts (MBHA) from one-pot Morita-Baylis-Hillman Reaction (MBHR) between aromatic aldehydes as eletrophiles and ethylene glycol diacrylate as Michael acceptor (35-94% yields) using cheap and green conditions. The bioactivities were evaluated against promastigote form of Leishmania donovani. All homodimers showed to be more potent than corresponding monomers. It is worth highlighting that the halogenated homodimers 17 and 18 (0.50μM) is almost 400 times more active than the corresponding monomer 10 and 1.24 times more potent than the second-line drug amphotericin B (0.62μM). Moreover, the selectivity index to 18 is very high (SIrb>400) far better than amphotericin B (SIrb=18.73). This is the first report of twin drugs strategy applied on Morita-Baylis-Hillman adducts.
authors: Departamento de Química, Universidade Federal da Paraíba, Campus I, 58059-900 João Pessoa, PB, Brazil.
authors: Wagner A V
authors: WAV
authors: da Silva
authors: Departamento de Química, Universidade Federal da Paraíba, Campus I, 58059-900 João Pessoa, PB, Brazil.
authors: Daniele C
authors: DC
authors: Rodrigues
authors: Departamento de Química, Universidade Federal da Paraíba, Campus I, 58059-900 João Pessoa, PB, Brazil.
authors: Ramon G
authors: RG
authors: de Oliveira
authors: Departamento de Química, Universidade Federal da Paraíba, Campus I, 58059-900 João Pessoa, PB, Brazil.
authors: Rhuan K S
authors: RKS
authors: Mendes
authors: Departamento de Química, Universidade Federal da Paraíba, Campus I, 58059-900 João Pessoa, PB, Brazil.
authors: Tayná R
authors: TR
authors: Olegário
authors: Departamento de Biotecnologia, Universidade Federal da Paraíba, Campus I, 58059-900 João Pessoa, PB, Brazil.
authors: Juliana C
authors: JC
authors: Rocha
authors: Departamento de Biotecnologia, Universidade Federal da Paraíba, Campus I, 58059-900 João Pessoa, PB, Brazil.
authors: Tatjana S L
authors: TSL
authors: Keesen
authors: Departamento de Química, Universidade Federal da Paraíba, Campus I, 58059-900 João Pessoa, PB, Brazil. Electronic address: claudio@quimica.ufpb.br.
authors: Claudio G
authors: CG
authors: Lima-Junior
authors: Departamento de Química, Universidade Federal da Paraíba, Campus I, 58059-900 João Pessoa, PB, Brazil. Electronic address: mlaav@quimica.ufpb.br.
authors: Mário L A A
authors: MLAA
authors: Vasconcellos
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019281:Dimerization; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents
keywords: Homodimers; Leishmania donovani; Morita–Baylis–Hillman adducts; Twin drugs