Synthesis and cytotoxic activity of α-santonin derivatives

Arantes, Francisco F. P.; Barbosa, Luiz C. A.; Alvarenga, Elson S.; Demuner, Antônio J.; Bezerra, Daniel P.; Ferreira, José R.O.; Costa-Lotufo, Letı́cia V.; Pessoa, Cláudia; Moraes, Manoel Odoríco de

doi:10.1016/j.ejmech.2009.03.036

Cited by 49 publications

(47 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, the human B-cell ALL cell lines Reh and RS4;11 displayed highest sensitivity to PPD among the tested cell lines and appeared in a time-and dose-dependent manner. In contrast, normal PBMC, which are commonly used for toxicity studies [29,30], were much less sensitive to PPD. These data suggest that PPD at effective dose resulting in growth inhibition of ALL cells may have little toxicity to normal cells.…”

Section: Discussionmentioning

confidence: 89%

Anti-cancer effects of 20(S)-protopanoxadiol on human acute lymphoblastic leukemia cell lines Reh and RS4;11

et al. 2010

View full text Add to dashboard Cite

Although the treatment outcome of acute lymphoblastic leukemia (ALL) has been improved in the past decades by combination chemotherapy, toxic side-effects of chemotherapeutics remain a major problem. Therefore, new alternative agents with low toxicity are urgently needed. Natural products provide a rich source of screening potential anti-cancer drugs. 20(S)-protopanoxadiol (PPD), a major gastrointestinal metabolic product of ginsenosides, exhibits promising anti-cancer activity with low toxicity. However, the anti-cancer activity of PPD against ALL has not been evaluated. In this study, we examined the anti-cancer effect of PPD on ALL cell lines Reh and RS4;11. The growth of leukemia cells and normal cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cell cycle, apoptosis and differentiation was determined by flow cytometry. The results showed that PPD inhibited the growth of Reh and RS4;11 cells, but had little toxicity to peripheral blood mononuclear cells (PBMC). PPD also blocked cell cycle progression from G0/G1 phase and induced cell differentiation. However, cell apoptosis was not affected. These data indicate that PPD exerts anti-cancer effects by stimulating differentiation and inhibiting growth and cell cycle progression of ALL cells.

show abstract

Section: Discussionmentioning

confidence: 89%

Anti-cancer effects of 20(S)-protopanoxadiol on human acute lymphoblastic leukemia cell lines Reh and RS4;11

et al. 2010

View full text Add to dashboard Cite

show abstract

“…In most cases, the biological activity of SQLs is related to the a-methylene-g-lactone functionality, which is prone to react with suitable nucleophiles as sulfhydryl groups of cysteine in a Michael addition type reaction [10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…The semi-empirical PM6 method was employed to calculate atomic and molecular descriptors of 20 SQLs reported in our previous works [16,28] as cytotoxic agents.…”

Section: Introductionmentioning

confidence: 99%

A quantum chemical and chemometric study of sesquiterpene lactones with cytotoxicity against tumor cells

Arantes

Barbosa

Maltha

et al. 2011

Journal of Chemometrics

Self Cite

View full text Add to dashboard Cite

The semi-empirical molecular orbital method PM6 was employed to calculate a set of molecular descriptors of 20 sesquiterpene lactones (SQLs) with cytotoxicity against HL-60 (leukemia) tumor cells. The principal component analysis (PCA) and hierarchical cluster analysis (HCA) methods were used to obtain possible relationships between the calculated descriptors and the biological activity of the lactones. Four descriptors were identified as responsible for the separation between the active and inactive compounds: E HOMO (highest occupied molecular orbital energy); Q11 (net atomic charge on C11); Q12 (net atomic charge on C12) and Q13 (net atomic charge on C13). These results indicated that the presence of the a-methylene-g-lactone group has a significant role in the mechanism by which SQLs exert their biological activities.

show abstract

“…In this context emerge other interesting compounds such as the alpha-santonin derivatives (Figure 6) a sesquiterpene lactone isolated from Artemisia santonica. The compounds with higher activity showed as common structural feature the presence of an alpha-methylidene-gamma-butyrolactone moiety in their structures (Arantes et al, 2009). This hypothesis has been corroborated in other tumoral cell lines.…”

Section: Selenide and Diselenide Derivativesmentioning

confidence: 99%