11a-N-tosyl-5-carbapterocarpans: Synthesis, antineoplastic evaluation and in silico prediction of ADMETox properties

Mendes, Joseane A.; Salustiano, Eduardo J.; Pires, Carulini de S.; Oliveira, Thais Silva de; Barcellos, Júlio C. F.; Cifuentes, Jhonny M.C.; Costa, Paulo R.R.; Rennó, Magdalena N.; Buarque, Camilla D.

doi:10.1016/j.bioorg.2018.07.004

Cited by 10 publications

(10 citation statements)

References 32 publications

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“…Communications candidates targeting diseases such as cancers and neurodegenerative diseases, [16] but only racemic samples have so far been used in biological testing owing to a shortage of enantioselective methods. [17] To understand the origin of the enantioselectivity in the model reaction (Figure 3), we performed DFT calculations for the reaction pathway at the wB97X-D/6-31G(d)/SDD level.…”

Section: Angewandte Chemiementioning

confidence: 99%

Asymmetric Three‐Component Heck Arylation/Amination of Nonconjugated Cyclodienes

et al. 2020

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Substituted cyclohexylamines are becoming increasingly important in drug discovery. Asymmetric Heck insertion/amination of nonconjugated cyclodienes proceeds to give 5‐aryl cyclohexenylamines with good enantioselectivity and exclusive trans configurations. Primary and secondary anilines, indoline, and benzylamines are suitable amines. The weakly donating diphosphite Kelliphite forms a deep unsymmetrical pocket, which is essential for stereoselective anti attack of amines.

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Section: Angewandte Chemiementioning

confidence: 99%

Asymmetric Three‐Component Heck Arylation/Amination of Nonconjugated Cyclodienes

et al. 2020

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“…This effect was more pronounced in MDA-MB-231 than MCF-7 cells, suggesting that the genetic background of the latter confers a higher sensitivity to LQB-223 than the former. In silico studies suggested that the biological effects observed upon exposure to LQB-223 are explained by the n-tosyl moiety [11].…”

Section: Discussionmentioning

confidence: 99%

“…LQB-223 antitumor activity involved suppression of proliferation, G2/M arrest, and apoptosis induction, which suggests that it might exhibit pleiotropic effects towards breast cancer cells. LQB-223-induced effects towards cancer cells have been recently attributed to its N-tosyl group [11] and potentially involve hydrophobic interaction with DNA [12].…”

Section: Introductionmentioning

confidence: 99%

The LQB-223 Compound Modulates Antiapoptotic Proteins and Impairs Breast Cancer Cell Growth and Migration

Lemos

Longo

Mendonça

et al. 2019

IJMS

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Drug resistance represents a major issue in treating breast cancer, despite the identification of novel therapeutic strategies, biomarkers, and subgroups. We have previously identified the LQB-223, 11a-N-Tosyl-5-deoxi-pterocarpan, as a promising compound in sensitizing doxorubicin-resistant breast cancer cells, with little toxicity to non-neoplastic cells. Here, we investigated the mechanisms underlying LQB-223 antitumor effects in 2D and 3D models of breast cancer. MCF-7 and MDA-MB-231 cells had migration and motility profile assessed by wound-healing and phagokinetic track motility assays, respectively. Cytotoxicity in 3D conformation was evaluated by measuring spheroid size and performing acid phosphatase and gelatin migration assays. Protein expression was analyzed by immunoblotting. Our results show that LQB-223, but not doxorubicin treatment, suppressed the migratory and motility capacity of breast cancer cells. In 3D conformation, LQB-223 remarkably decreased cell viability, as well as reduced 3D culture size and migration. Mechanistically, LQB-223-mediated anticancer effects involved decreased proteins levels of XIAP, c-IAP1, and Mcl-1 chemoresistance-related proteins, but not survivin. Survivin knockdown partially potentiated LQB-223-induced cytotoxicity. Additionally, cell treatment with LQB-223 resulted in changes in the mRNA levels of epithelial-mesenchymal transition markers, suggesting that it might modulate cell plasticity. Our data demonstrate that LQB-223 impairs 3D culture growth and migration in 2D and 3D models of breast cancer exhibiting different phenotypes.

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“…Dentre os compostos sintetizados, destacou-se o LQB-223 (Figura 9), um Ntosil-aza-carbapterocarpano que apresentou atividade antiproliferativa semelhante ao antineoplásico doxorrubicina em linhagens de células de melanoma (MDA-MB435), ação anticâncer em linhagens de leucemia (HL-60) e câncer de cólon (HCT-8), uma potente atividade antileshimanial in vitro e antimalarial em ensaios in vivo (BUARQUE et al, 2010(BUARQUE et al, , 2011(BUARQUE et al, , 2014CORTOPASSI et al, 2014;LEMOS et al, 2016;MENDES et al, 2018;SILVA et al, 2017). (BUARQUE et al, 2014).…”

Section: íNdice De Esquemasunclassified

“…O presente estudo também demonstrou a importância da presença da sulfonamida como um grupo privilegiado. Neste contexto, identificamos que a remoção do grupo protetor reduz drasticamente a atividade biológica nas linhagens conforme dados de IC50 do composto 125a (MENDES et al, 2018).…”

Section: Tentativa De Aza-arilação Do Aza-carbapterotiocarpanounclassified

Síntese De N-Tosil Aza-Carbapterocarpanos E Espiro Iso-Indolinas Com Potencial Ação Antitumoral

MENDES¹

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11a-N-tosyl-5-carbapterocarpans: Synthesis, antineoplastic evaluation and in silico prediction of ADMETox properties

Cited by 10 publications

References 32 publications

Asymmetric Three‐Component Heck Arylation/Amination of Nonconjugated Cyclodienes

Asymmetric Three‐Component Heck Arylation/Amination of Nonconjugated Cyclodienes

The LQB-223 Compound Modulates Antiapoptotic Proteins and Impairs Breast Cancer Cell Growth and Migration

Síntese De N-Tosil Aza-Carbapterocarpanos E Espiro Iso-Indolinas Com Potencial Ação Antitumoral

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