Structure-anti-leukemic activity relationship study of ortho-dihydroxycoumarins in U-937 cells: Key role of the δ-lactone ring in determining differentiation-inducing potency and selective pro-apoptotic action

Vázquez, Ramiro; Riveiro, María E.; Vermeulen, Mónica; Alonso, Ernesto; Mondillo, Carolina; Facorro, Graciela; Piehl, Lidia Leonor; Gómez, Natalia; Moglioni, Albertina G.; Fernández, Natalia Cristina; Baldi, Alberto; Shayo, Carina; Davio, Carlos

doi:10.1016/j.bmc.2012.07.043

Cited by 29 publications

(23 citation statements)

References 34 publications

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“…However, this derivative was reported to be effective only at doses higher than 100 mM, which is in agreement with our present observations. A previous SAR study that has examined the effect of coumarins on U-937 leukemic cells have shown that o-dihydroxy coumarins show selective toxicity towards cancer cells (Vázquez et al, 2012). Another report has shown that 7,8-DHMC is a potent anticancer agent that selectively targets leukemia cells (Vázquez et al, 2013).…”

Section: Resultsmentioning

confidence: 99%

Structure–activity relationship studies of 4-methylcoumarin derivatives as anticancer agents

Miri

Nejati

Saso

et al. 2015

Pharmaceutical Biology

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Materials and methods:We synthesized 27 coumarin derivatives (mostly having 4-methyl moiety) and examined their cytotoxic effect on three human cancer cell lines, K562 (chronic myelogenous leukemia), LS180 (colon adenocarcinoma), and MCF-7 (breast adenocarcinoma) by MTT reduction assay. Screened compounds included 7-hydroxy-4-methylcoumarins (7-HMCs), 7-acetoxy-4-methylcoumarins (7-AMCs), and different dihydroxy-4-methylcoumarin (DHMC) and diacetoxy-4-methylcoumarin (DAMC) derivatives. Some compounds with methoxy, amine, and bromine substitutions were also examined.Results: 7,8-DHMCs bearing alkyl groups at C3 position were the most effective subgroup, and of which, the most potent is compound 11, with an n-decyl chain at C3, which had IC 50 values of 42.4, 25.2, and 25.1 mM against K562, LS180, and MCF-7 cells, respectively. The second most active subgroup was 7,8-DAMCs containing ethoxycarbonylmethyl and ethoxycarbonylethyl moieties at C3 position. Compound 27 (6-bromo-4-bromomethyl-7-hydroxycoumarin), the only derivative containing bromine also showed reasonable cytotoxic activities (IC 50 range: 32.7-45.8 mM). Discussion and conclusion: This structure-activity relationship (SAR) study of 4-methylcoumarins shows that further investigation of these derivatives may lead to the discovery of novel anticancer agents.

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Section: Resultsmentioning

confidence: 99%

Structure–activity relationship studies of 4-methylcoumarin derivatives as anticancer agents

Miri

Nejati

Saso

et al. 2015

Pharmaceutical Biology

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“…However, Riveiro et al proved that alkoxy residue could potentiate the antiproliferative effects of coumarins [39]. Although the tested coumarins were devoid of catechol moiety, which could have contributed to the growth inhibitory activity [40], it is highly likely that the presence of isoprenoid residue in osthole and isoimperatorin has contributed to various pharmacological interactions, which gave rise to the proapoptotic activity [41]. Important coumarin apoptotic features such as free catechol and isoprenoid moieties are absent in braylin and oxypeucedanin.…”

Section: Discussionmentioning

confidence: 99%

Comparative Evaluation of Cytotoxic and Apoptogenic Effects of Several Coumarins on Human Cancer Cell Lines: Osthole Induces Apoptosis in p53-Deficient H1299 Cells

Shokoohinia

Hosseinzadeh

Alipour

et al. 2014

Advances in Pharmacological Sciences

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Natural products are excellent resources for finding lead structures for the development of chemotherapeutic agents. Coumarins are a class of natural compounds found in a variety of plants. In this study, we evaluated the cytotoxic potential of coumarins isolated from Prangos ferulacea (L.) Lindl. in PC3, SKNMC, and H1299 (p53 null) human carcinoma cell lines. Osthole proved to be an outstanding potent cytotoxic agent especially against PC3 cells. Isoimperatorin exhibited moderate inhibitory effect against SKNMC and PC3 cell lines. Oxypeucedanin and braylin did not display any cytotoxic activity. In the next set of experiments, the apoptotic potentials of osthole and isoimperatorin were investigated. Induction of apoptosis by isoimperatorin was accompanied by an increase in activation of caspase-3, -8, and -9 in SKNMC cells and caspase-3 and -9 in PC3 cells. Moreover, isoimperatorin induced apoptosis by upregulating Bax and Smac/DIABLO genes in PC3 and SKNMC cells. Osthole induced apoptosis by downregulating antiapoptotic Bcl-2 in only PC3 cells and upregulating the proapoptotic genes Bax and Smac/DIABLO in PC3, SKNMC, and H1299 cells. The effects of osthole on H1299 cells are important because the loss of p53 has been associated with poor clinical prognosis in cancer treatment.

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“…As cumarinas e seus derivados podem exercer atividade anticancerígena através de vários mecanismos: inibição da enzima telomerase, regulação negativa da expressão do oncogene (NASR et al, 2014) e entre as hidroxicumomarinas, a 7,8-hidroxicumarina pode demonstrar essa ação gerando estresse oxidativo devido à produção de livre espécies radicais em células cancerosas, o que leva a um efeito pró-apoptótico em células U-937 e HL-60 (VAZQUEZ et al, 2012).…”

Section: Resultsunclassified

AVALIAÇÃO DA ATIVIDADE CITOTÓXICA DA 3-HIDROXICUMARINA FRENTE À LINHAGEM CELULARHeLa

Oliveira¹,

Filho²,

Araújo³

et al. 2017

Anais Do 5º Encontro Brasileiro Para Inovação Terapêutica

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Structure-anti-leukemic activity relationship study of ortho-dihydroxycoumarins in U-937 cells: Key role of the δ-lactone ring in determining differentiation-inducing potency and selective pro-apoptotic action

Cited by 29 publications

References 34 publications

Structure–activity relationship studies of 4-methylcoumarin derivatives as anticancer agents

Structure–activity relationship studies of 4-methylcoumarin derivatives as anticancer agents

Comparative Evaluation of Cytotoxic and Apoptogenic Effects of Several Coumarins on Human Cancer Cell Lines: Osthole Induces Apoptosis in p53-Deficient H1299 Cells

AVALIAÇÃO DA ATIVIDADE CITOTÓXICA DA 3-HIDROXICUMARINA FRENTE À LINHAGEM CELULARHeLa

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