Potential antiproliferative effect of isoxazolo- and thiazolo coumarin derivatives on breast cancer mediated bone and lung metastases

Abstract

Potential antiproliferative effect of isoxazolo-and thiazolo coumarin derivatives on breast cancer mediated bone and lung metastasesThe study highlights the current progress in the development of coumarin scaffolds for drug discovery as novel anticancer agents in metastatic breast cancer. Eight compounds, combining the coumarin core and five membered heterocycles (isoxazoles and thiazoles) in hydrazinyldiene--chroman-2,4-diones, were characterized in terms of a potential antiproliferative effect on bone (SCP1833) and lung (SCP4175) metastatic breast cancer cell lines using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Cell viability was evaluated after 48 and 72 h of treatment and the 50 % inhibitory concentrations were determined. The results demonstrated dose-and time-dependent activity, with the most potent molecules having a thiazole moiety, without or with additional methyl group(s) attached to the carbon(s) at position(s) 5 and/or 4 in the thiazole ring. These molecules possessed significantly higher potency against both test cell lines compared to 4-hydroxycoumarin.

Hydrazinyldiene-chroman-2,4-diones in inducing growth arrest and apoptosis in breast cancer cells: Synergism with doxorubicin and correlation with physicochemical properties

“…Further dilutions were made in complete DMEM containing 10 % FBS. Cytotoxic effects of coumarin derivatives and 4-HC alone and in synergy with Doxo on MCF-7 cells were determined in 96-microwell plates by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and alamarBlue assay as previously described (3,11,13).…”

“…Considering all the above-mentioned information, compounds that combine coumarin core and isoxazoles or thiazoles in hydrazinyldiene-chroman-2,4-diones have been synthesized and structurally characterized in our previous studies (Table I) (3,11,12). Three compounds having thiazole moiety, 3-[2-(1,3-thiazol-2-yl)hydrazinylidene]chroman-2,4-dione (1c), 3-[2-(4-methyl-1,3-thiazol-2-yl)hydrazinylidene]chroman-2,4-dione (1d) and 3-[2-(4,5-dimethyl-1,3-thiazol-2-yl)hydrazinylidene]chroman-2,4-dione (1e), have been shown to exert more potent antiproliferative activity than the other synthesized compounds, inducing apoptosis in breast cancer cells MCF-7 and MDA-MB-231 (3) and in bone and lung metastatic cell lines from breast cancer SCP1833 and SCP4175 (11).…”

“…Three compounds having thiazole moiety, 3-[2-(1,3-thiazol-2-yl)hydrazinylidene]chroman-2,4-dione (1c), 3-[2-(4-methyl-1,3-thiazol-2-yl)hydrazinylidene]chroman-2,4-dione (1d) and 3-[2-(4,5-dimethyl-1,3-thiazol-2-yl)hydrazinylidene]chroman-2,4-dione (1e), have been shown to exert more potent antiproliferative activity than the other synthesized compounds, inducing apoptosis in breast cancer cells MCF-7 and MDA-MB-231 (3) and in bone and lung metastatic cell lines from breast cancer SCP1833 and SCP4175 (11). In this study, the synergistic effects of these three hydrazinyldiene-chroman-2,4-diones and Doxo on cell proliferation and apoptosis, cell cycle distribution and migration capacity of breast cancer cell lines MCF-7 were evaluated.…”

Crystal structure of 3-bromoacetyl-6-chloro-2H-1-benzopyran-2-one

“…For applications of coumarins, see: Kale & Patwardhan (2014); Eid et al (1994); Hsieh (2015); Ballazhi et al (2015); Wang (2015); Lanoot et al (2002); Morris & Russell (1971); Hooper et al (1982); Khalfan et al (1987). For related structures, see: Munshi et al (2004); Munshi & Guru Row (2006); Chopra et al (2006Chopra et al ( , 2007a…”

Synergy of novel coumarin derivatives and tamoxifen in blocking growth and inducing apoptosis of breast cancer cells

“…. Structure of the novel hydrazinylidiene-chroman-2,4-diones obtained after reaction of the coumarin with the corrsponding salts of the heterocyclic amines (Jashari et al, 2013;Ballazhi et al, accepted for publication).…”