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

Silva, Wagner A.V. da; Rodrigues, Daniele C.; Oliveira, Rogério de; Mendes, Rhuan Karlos Santos; Olegário, Tayná Rodrigues; Rocha, Juliana C.; Keesen, Tatjana Souza Lima; Lima-Júnior, Cláudio Gabriel; Vasconcellos, Mário L. A. A.

doi:10.1016/j.bmcl.2016.07.022

Cited by 21 publications

(7 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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 2016 we reported that the homodimer of MBHAs with a bromine atom as a substituent in the aromatic moiety showed very high anti- leishmania activity on L. donovani (0.50 μM) almost 400 times more active than the corresponding monomer and 1.24 times more potent than Amphotericin B (0.62 μM). Moreover, the selectivity index of the homodimer was very high (SI rb > 400), far better than Amphotericin B (SI rb = 18.73) [ 28 ]. These results demonstrate that the hybridization reactions were pivotal for the increase of leishmanicidal action and maintaining the absence of toxicity in macrophages and red blood cells of the hybrids, indicating that 9h is a promising compound for further biological studies.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2017

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

et al. 2017

View full text Add to dashboard Cite

show abstract

“…We have recently reported preliminary synthetic efforts aimed at the construction of homodimers of 7-anilinoisoquinolinequinones such as B and C, to produce twin drugs of these cytotoxic pharmacophores [ 12 ]. The linkage of two identical pharmacophoric entities, generating an “identical twin drug” or homodimer derivative, is a classical strategy used in medicinal chemistry to produce more potent and/or selective drugs compared to the single entities [ 13 , 14 , 15 , 16 ]. Our efforts to prepare homodimers from isoquinolinequinones and symmetric aryldiamines such as p -phenylendiamine, benzidine, and dapsone were unsuccessful, since the diamines act as mononucleophiles to produce the corresponding arylaminoisoquinolinequinones [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Preparation of Novel Homodimers Derived from Cytotoxic Isoquinolinequinones. A Twin Drug Approach

et al. 2018

View full text Add to dashboard Cite

The synthesis of five novel homodimers is reported based on the anilinoisoquinolinequinone scaffold. In these twin-drug derivatives, two units of the anilinoquinone pharmacophores are linked through a methylene spacer. The formation of dimers was achieved by reaction of isoquinolinequinones with 4, 4′-diaminodiphenylmethane via a sequence of two oxidative amination reactions. A preliminary in vitro screening of the homodimers reveals moderate to high cytotoxic activities against MDA-MB-21 breast adenocarcinoma and B16-F10 murine metastatic melanoma cell lines. The asymmetrical homodimer 15 stands out due to its cytotoxic potencies at submicromolar concentrations and high selectivity index (mean IC50 = 0.37 μM; SI = 6.97) compared to those of etoposide (mean IC50 = 3.67; SI = 0.32) and taxol (mean IC50 = 0.35; SI = 0.91) employed as reference anticancer drugs.

show abstract

“…BH reaction template also offers high tunability at three different places. This reaction has been extensively investigated for various types of pharmaceutical development [ 17 – 24 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of Baylis-Hillman Reaction Derived Imidazole and Triazole Cinnamates as Antifungal Agents

Nelson

Williams

Jonnalagadda

et al. 2018

International Journal of Medicinal Chemistry

View full text Add to dashboard Cite

Allylic acetates derived from Baylis-Hillman reaction undergo efficient nucleophilic isomerization with imidazoles and triazoles to provide imidazolylmethyl and triazolylmethyl cinnamates stereoselectively. Antifungal evaluation of these derivatives against Cryptococcus neoformans exhibits good minimum inhibitory concentration values. These compounds exhibit low toxicity in proliferating MCF-7 breast cancer cell line. Structure activity relationship studies indicate that halogenated aromatic derivatives provide better antifungal activity.

show abstract

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

Cited by 21 publications

References 22 publications

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

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

Preparation of Novel Homodimers Derived from Cytotoxic Isoquinolinequinones. A Twin Drug Approach

Synthesis and Evaluation of Baylis-Hillman Reaction Derived Imidazole and Triazole Cinnamates as Antifungal Agents

Contact Info

Product

Resources

About