Quantitative Structure–Cytotoxicity Relationship of 2-(<i>N</i>-cyclicamino)chromone Derivatives

Shi, Huidong; Nagai, Junko; Sakatsume, Tsukasa; Bandow, Kenjiro; Okudaira, Noriyuki; Sakagami, Hiroshi; Tomomura, Mineko; Tomomura, Akito; Uesawa, Yoshihiro; Takao, Koichi; Sugita, Yoshiaki

doi:10.21873/anticanres.12674

Cited by 11 publications

(34 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Human OSCC cell lines (Ca9-22, derived from gingival tissue; HSC-2, HSC-3. HSC-4, derived from tongue) and human normal oral mesenchymal cells (HGF, HPLF, HPC) at 10-18 population doubling levels were cultured at 37˚C in DMEM supplemented with 10% heat-inactivated FBS, 100 units/ml, penicillin G and 100 μg/ml streptomycin sulfate under a humidified 5% CO 2 atmosphere, as described previously (20,21).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Quantitative Structure–Cytotoxicity Relationship of 2-Styrylchromones

et al. 2019

Self Cite

View full text Add to dashboard Cite

Background/Aim: Studies of biological activity of 2styrylchromone derivatives focusing on antioxidant, antiinflammatory, antiviral and antitumor activity are limited. In this study, eighteen synthetic 2-styrylchromone derivatives were investigated for their cytotoxicity against human malignant and non-malignant cells, and then subjected to quantitative structure-activity relationship (QSAR) analysis. Materials and Methods: Tumor-specificity was calculated by the ratio of mean 50% cytotoxic concentration (CC 50) against four normal oral cells to that against oral squamous cell carcinoma cell lines. Induction of apoptosis and growth arrest were evaluated by cellcycle analysis. For QSAR analysis, 3,117 types of physicochemical, structural, and quantum chemical features were calculated from the most stabilized structure of 2styrylchromone derivatives. Results: Two 2-styrylchromone derivatives in which a methoxy group was introduced at the 4position of the benzene ring showed tumor-specificity equivalent to or higher than doxorubicin in TS value. These compounds accumulated the subG 1 and G 2 /M phase cells, suggesting the induction of apoptosis. Their tumor-specificity can be explained mainly by molecular shape and electronic state. Conclusion: These findings suggest the applicability of 2-styrylchromone to develop safe and effective anticancer agents as seed compounds. Our group recently found that low-molecular weight natural polyphenols, such as tannins and flavonoids showed very low anticancer activity (evaluated by tumor-specificity with human cultured malignant and none-malignant cells) (1). On the other hand, chemical modification of chromone, two ring backbone structure present in flavonoids, yielded derivatives with much higher tumor-specificity (2, 3). 2-Styrylchromone is a derivative having a styryl group bonded to the 2-position of the chromone skeleton. Synthetic 2styrylchromone derivatives have been reported to show radical scavenging (4, 5), anti-inflammatory (6), hepatoprotective (7), neuroprotective (8-10), anti-human immunodeficiency virus (11), anti-norovirus (12), anti-rhinovirus (13, 14), antitumor (15-18), and monoamine oxidase B inhibiting (19) activity. However, very few studies tested their cytotoxicity against normal cells (16). In the present study, we investigated the cytotoxicity of eighteen synthetic 2-styrylchromone derivatives (Figure 1) against four human oral squamous cell carcinoma (OSCC) cells lines (Ca9-22, HSC-2, HSC-3, HSC-4) and three human normal oral mesenchymal cells [human gingival fibroblast (HGF), human periodontal ligamental fibroblast (HPLF) and human pulp cell (HPC)], and performed quantitative structure-activity relationship (QSAR) analysis. Materials and Methods Materials.

show abstract

mentioning

confidence: 99%

“…After 48 h, the medium was replaced with fresh medium containing (1/2) 2 serially diluted test compounds. Cells were incubated for 48 h and the relative viable cell number was then determined in triplicate by MTT method, as described previously (20,21). Control cells were treated with the same amounts of DMSO and the cell damage induced by DMSO was subtracted.…”

mentioning

confidence: 99%

Quantitative Structure–Cytotoxicity Relationship of 2-Styrylchromones

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Their tumor specificity was also significantly positively correlated lipophilicity, 3D shape, and negative charge (p-values from 1.45×10 -6 to 3.18×10 -8 ) (Figure 6). Taken together, these data suggest that ANTICANCER RESEARCH 38: 4459-4467 (2018) 4466 When we compared the A series of compounds of 3-(Ncyclicamino)chromones (this study) with their structural isomers, 2-(N-cyclicamino)chromones (13), there were common properties: 4-phenyl-1-piperazinyl derivatives (3a) of both groups had the highest cytotoxicity against four human OSCC cell lines, followed by 4-phenyl-1-piperidinyl derivatives (2a) in both cases [ Table I and (13)]. Furthermore, TS of both groups of compounds were correlated with 3D structure (mass or shape) reflected by Mor17v, Mor17m and Mor22m for 2-(Ncyclicamino)chromones, and FCASA-, Chi_G/D, VE3sign_G, J_D/Dt for 3-(N-cyclicamino) chromones.…”

Section: Discussionmentioning

confidence: 70%

“…We recently reported that 7-methoxy-2-(4-morpholinyl)-4H-1-benzopyran-4-one [5c which had the highest tumor specificity among 15 2-(N-cyclicamino)chromone derivatives (13)], led to cytotoxic growth inhibition in OSCC cell lines without induction of apoptosis. These results suggest that these structural isomers, 2-(N-cyclicamino)chromones and 3-(N-cyclicamino)chromones, have no apoptosis-inducing activity, despite exhibiting different modes of growth inhibition (either cytotoxic or cytostatic).…”

Section: Discussionmentioning

confidence: 99%

“…We recently found that among 15 such 2-(N-cyclicamino)chromone derivatives, 7-methoxy-2-(4-morpholinyl)-4H-1-benzopyran-4-one had the highest tumor specificity, comparable with that of doxorubicin, without induction of apoptosis. Tumor specificity of these derivatives was correlated with molecular shape, especially 3D structure (13).…”

Section: Background/aim: 4h-1-benzopyran-4-ones (Chromones) Provide Amentioning

confidence: 99%

See 1 more Smart Citation