Synthesis and activity of novel homodimers of Morita-Baylis-Hillman adducts against Leishmania donovani: A twin drug approach

Wagner A V da Silva; Daniele C Rodrigues; Ramon G de Oliveira; Rhuan K S Mendes; Tayná R Olegário; Juliana C Rocha; Tatjana S L Keesen; Claudio G Lima-Junior; Mário L A A Vasconcellos

doi:10.1016/j.bmcl.2016.07.022

Synthesis and activity of novel homodimers of Morita-Baylis-Hillman adducts against Leishmania donovani: A twin drug approach

Bioorg Med Chem Lett. 2016 Sep 15;26(18):4523-4526. doi: 10.1016/j.bmcl.2016.07.022. Epub 2016 Aug 1.

Authors

Wagner A V da Silva¹, Daniele C Rodrigues¹, Ramon G de Oliveira¹, Rhuan K S Mendes¹, Tayná R Olegário¹, Juliana C Rocha², Tatjana S L Keesen², Claudio G Lima-Junior³, Mário L A A Vasconcellos⁴

Affiliations

¹ Departamento de Química, Universidade Federal da Paraíba, Campus I, 58059-900 João Pessoa, PB, Brazil.
² Departamento de Biotecnologia, Universidade Federal da Paraíba, Campus I, 58059-900 João Pessoa, PB, Brazil.
³ Departamento de Química, Universidade Federal da Paraíba, Campus I, 58059-900 João Pessoa, PB, Brazil. Electronic address: [email protected].
⁴ Departamento de Química, Universidade Federal da Paraíba, Campus I, 58059-900 João Pessoa, PB, Brazil. Electronic address: [email protected].

PMID: 27520941
DOI: 10.1016/j.bmcl.2016.07.022

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.

Keywords: Homodimers; Leishmania donovani; Morita–Baylis–Hillman adducts; Twin drugs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiprotozoal Agents / chemical synthesis*
Antiprotozoal Agents / chemistry
Antiprotozoal Agents / pharmacology*
Dimerization
Hemolysis / drug effects
Humans
Leishmania donovani / drug effects*

Substances

Antiprotozoal Agents