Synthesis, evaluation against Leishmania amazonensis and cytotoxicity assays in macrophages of sixteen new congeners Morita–Baylis–Hillman adducts

Silva, Fábio P.L.; Assis, Priscilla Anne Castro de; G.L., Cláudio; Andrade, Natália G. de; Cunha, Saraghina Maria Donato da; Oliveira, Márcia Rosa de; Vasconcellos, Mário L. A. A.

doi:10.1016/j.ejmech.2011.06.036

Cited by 16 publications

(11 citation statements)

References 54 publications

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“…Subsequently, effective antipromastigote activity is demonstrated for Leishamania amazonensis , particularly in relation to the DHDE‐1MeO produced. The analysis of antipromastigote activity is a widely used method for investigating potential new drugs for the treatment of leishmaniasis .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antileishmanial Activity of Natural Dehydrodieugenol and Its Mono‐ and Dimethyl Ethers

Rodrigues

Barbosa-Filho

Oliveira

et al. 2016

Chemistry & Biodiversity

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The study of chemistry of naturally occurring compounds and the synthesis of their derivatives is fundamentally important for the development of new drugs. In this work, dehydrodieugenol (DHDE) was obtained through oxidative coupling of eugenol, promoted by an aqueous mixture of potassium ferricyanide (K3 [Fe(CN)6 ]) and NH3 · H2 O. The partial methoxylation of DHDE with MeI and K2 CO3 mainly resulted in the molecular-shaped monomethyl ether (DHDE-1MeO) and its dimethyl ether derivative (DHDE-2MeO). The products from the reactions were characterized by (1) H- and (13) C-NMR spectroscopy. Additionally, these studies have reported the antileishmanial activity of DHDE against Leishmania amazonensis (IC50 value of 42.20 μg ml(-1) ) and shown that partial methoxylation of DHDE results in a significant increase in its antiparasitic activity (IC50 value of 13.68 μg ml(-1) ). Based on in vitro bioassays, DHDE-1MeO has shown the highest leishmanicidal activity in promastigota form. Production by direct one-step synthesis of this monomethoxylated compound can be considered to be a cost-effective and environmentally friendly method with a short reaction time.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Antileishmanial Activity of Natural Dehydrodieugenol and Its Mono‐ and Dimethyl Ethers

Rodrigues

Barbosa-Filho

Oliveira

et al. 2016

Chemistry & Biodiversity

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“…The hybrid 9h presents the bromine atom in its chemical structure. In previous works described by our research group we highlight the association between leishmanicidal activity and the presence of bromine atoms as substituents in the aromatic moiety [ 9 , 18 , 19 , 20 , 28 ]. Among the works we highlight two examples.…”

Section: Resultsmentioning

confidence: 99%

“…In connection with our interest in the discovery of new Morita-Baylis-Hillman adducts with promising leishmanicidal and other bioactivities [ 5 , 18 , 19 , 20 , 21 ], we present here the design, synthesis, and in vitro screening against Leishmania donovani of sixteen new molecular hybrids ( 8a – h and 9a – h , Figure 2 ). It is important to note here that our design is based on the fact that inhibitors of opioid receptors participate in the mechanism of action against leishmaniasis interfering with the immune system, not only participating in the function of the immune cells, but also modulating innate and acquired immune responses [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 16 New Hybrids from Tetrahydropyrans Derivatives and Morita˗Baylis˗Hillman Adducts: In Vitro Screening against Leishmania donovani

et al. 2017

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Leishmaniases are a group of neglected tropical diseases (NTDs) caused by protozoan parasites from >20 Leishmania species. Visceral leishmaniasis (VL), also known as kala-aza, is the most severe form of leishmaniasis, usually fatal in the absence of treatment in 95% of cases. The Morita-Baylis-Hillman adducts (MBHAs) are being explored as drug candidates against several diseases, one of them being leishmaniasis. We present here the design, synthesis and in vitro screening against Leishmania donovani of sixteen new molecular hybrids from analgesic/anti-inflammatory tetrahydropyrans derivatives and Morita-Baylis-Hillman adducts. First, acrylates were synthesized from analgesic/anti-inflammatory tetrahydropyrans using acrylic acid under TsOH as a catalyst (70%–75% yields). After the 16 new MBHAs were prepared in moderate to good yields (60%–95%) promoted by microwave irradiation or low temperature (0 °C) in protic and aprotic medium. The hybrids were evaluated in vitro on the promastigote stage of Leishmania donovani by determining their inhibitory concentrations 50% (IC50), 50% hemolysis concentration (HC50), selectivity index (HC50/IC50,), and comparing to Amphotericin B, chosen as the anti-leishmanial reference drug. The hybrid which presents the bromine atom in its chemical structure presents high leishmanicide activity and the high selectivity index in red blood cells (SIrb > 180.19), compared with the highly-toxic reference drug (SIrb = 33.05), indicating that the bromine hybrid is a promising compound for further biological studies.

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“…They consist on the minimal concentration that inhibits 50 % of parasites growth (IC 50 ), using Elisa/ MTT method (enzyme-linked immunosorbent assay/3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) (Junior et al, 2010;Silva et al, 2011). For QSAR analysis, the values were converted to -LogIC 50 (pIC 50 ) to reduce standard deviation and to make the larger values correspond to the most active compounds (Table 1).…”

Section: Experimental Datamentioning

confidence: 99%

“…In 2011, the bioisosterism strategy (Lima and Barreiro, 2005) was used to obtain a new series of 16 aromatic MBHA, obtained by reaction between aromatic aldehydes and propyl acrylate or hydroxyl ethyl acrylate (17i-32p, Fig. 1), which were bio-evaluated against the promastigote forms of L. amazonensis and L. Chagasi (Silva et al, 2011). These accumulated data could be used on construction of quantitative structure-activity relationships (QSAR) models.…”

Section: Introductionmentioning

confidence: 99%

Selection of 2D/3D molecular descriptors and QSAR modeling of aromatic Morita–Baylis–Hillman adducts with leishmanicidal activities

2014

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Aromatic Morita-Baylis-Hillman adducts (MBHA) are a class of compounds which have shown antiparasitic potential in tropical diseases (such as Leishmaniases, Chagas disease, malaria). MBHA analogs have been studied by our research group on synthetical, theoretical, and bioactivity aspects. We present here a variable selection of 2D and 3D molecular descriptors, followed by quantitative structure-activity relationship (QSAR) modeling of thirty-two MBHA bioactive against the parasite Leishmania amazonensis. Descriptors were calculated by E-Dragon online platform. Variable selection was performed using ordered predictor selector (OPS) algorithm, and QSAR models were obtained using partial least squares (PLS). Internal and external validation parameters indicated a robust and predictive model, which may help the synthesis of most potent leishmanicidal compounds.

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Synthesis, evaluation against Leishmania amazonensis and cytotoxicity assays in macrophages of sixteen new congeners Morita–Baylis–Hillman adducts

Cited by 16 publications

References 54 publications

Synthesis and Antileishmanial Activity of Natural Dehydrodieugenol and Its Mono‐ and Dimethyl Ethers

Synthesis and Antileishmanial Activity of Natural Dehydrodieugenol and Its Mono‐ and Dimethyl Ethers

Synthesis of 16 New Hybrids from Tetrahydropyrans Derivatives and Morita˗Baylis˗Hillman Adducts: In Vitro Screening against Leishmania donovani

Selection of 2D/3D molecular descriptors and QSAR modeling of aromatic Morita–Baylis–Hillman adducts with leishmanicidal activities

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