Open Access

Synthesis and cytotoxic evaluation of some new[1,3]dioxolo[4,5-g]chromen-8-one derivatives

  • Eskandar Alipour1,
  • Zinatsadat Mousavi1,
  • Zahra Safaei1,
  • Mahboobeh Pordeli2,
  • Maliheh Safavi3,
  • Loghman Firoozpour4,
  • Negar Mohammadhosseini5,
  • Mina Saeedi5,
  • Sussan Kabudanian Ardestani2,
  • Abbas Shafiee5 and
  • Alireza Foroumadi5Email author
DARU Journal of Pharmaceutical Sciences201422:41

https://doi.org/10.1186/2008-2231-22-41

Received: 25 December 2013

Accepted: 16 April 2014

Published: 2 May 2014

Abstract

Background

Homoisoflavonoids are naturally occurring compounds belong to flavonoid classes possessing various biological properties such as cytotoxicity. In this work, an efficient strategy for the synthesis of novel homoisoflavonoids, [1,3]dioxolo[4,5-g]chromen-8-ones, was developed and all compounds were evaluated for their cytotoxic activities on three breast cancer cell lines.

Methods

Our synthetic route started from benzo[d][1,3]dioxol-5-ol which was reacted with 3-bromopropanoic acid followed by the reaction of oxalyl chloride to afford 6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one. The aldol condensation of the later compound with aromatic aldehydes led to the formation of the title compounds. Five novel derivatives 4a-e were tested for their cytotoxic activity against three human breast cancer cell lines including MCF-7, T47D, and MDA-MB-231 using the MTT assay.

Results

Among the synthesized compounds, 7-benzylidene-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4a) exhibited the highest activity against three cell lines. Also the analysis of acridine orange/ethidium bromide staining results revealed that 7-benzylidene-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4a) and 7-(2-methoxybenzylidene)-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4b) induced apoptosis in T47D cell line.

Conclusion

Finally, the effect of methoxy group on the cytotoxicity of compounds 4b-4d was investigated in and it was revealed that it did not improve the activity of [1,3]dioxolo[4,5-g]chromen-8-ones against MCF-7, T47D, and MDA-MB-231.

Keywords

Homoisoflavonoids [1,3]dioxolo[4,5-g]chromen-8-one Cancer Cytotoxic activity

Background

Homoisoflavonoids, naturally occurring compounds belong to flavonoid classes and possess a wide spectrum of biological properties such as anti-inflammatory [1], antioxidant [2], antiproliferative [3], antifungal [4], antiviral [5], and antimutagenic activities [6]. They mainly include a chromanone, chromone, or chromane skeleton and are ubiquitous in plants such as Ophiopogon[7], Polygonatum[8], Scilla[9], Eucomis[10], and Muscari[11]. Recently, several homoisoflavonoids have been successfully isolated from plants and evaluated for their bioactivities [12, 13].

Chalcones have been the center of attention owing to their significant biological activities [1418]. Also they are the most important precursors for the formation of α, β-unsaturated carbonyl system in flavonoid classes. Homoisoflavonoids including chalcone system have shown selective biological activities [19]. The isolated natural homoisoflavonoids having 3-benzylidenechroman-4-one skeleton were found to be potent and selective MAO-B inhibitors. Compounds involving benzylidene chromanone have depicted significant medicinal properties such as antioxidant [20], anticancer [21], anti-inflammatory [22], anti-human-immune deficiency virus (HIV-I) activities [23].

Two naturally occurring homoisoflavonoids, bonducellin [24] 1 and eucomin [25] 2 (Figure 1), isolated from Caesalpiniabonducella and Eucomis bicolor BAK (Liliaceae) were considered. These compounds and their synthetic analogues have shown important biological properties such as anti-tuberculosis activity [26] and inhibition of protein tyrosine kinase (PTK) [27].
Figure 1

Bonducellin 1 and Eucomin 2.

On the synthesis of bioactiveheterocycles containing oxygen specially chalcones and homoisoflavonoids [9, 21, 28, 29]; herein, we focused on new substituted [1,3]dioxolo[4,5-g]chromen-8-one derivatives 4 to profit from both chalcones and homoisoflavonoids (Scheme 1). Then, we evaluated their cytotoxic activities against three human breast cancer cell lines; MCF-7, T47D, and MDA-MB-231 using the MTT assay.
Scheme 1

Synthesis of [1,3]dioxolo[4,5- g ]chromen-8-ones 4. (a) NaOH, Na2CO3, Br(CH2)2COOH, H2O, reflux, (b) oxalyl chloride, SnCl4, benzene, (c) aromatic aldehydes, HCl (g), 0°C.

Methods

Chemistry

All starting materials, reagents, and solvents were prepared from Merck (Germany). Melting points were determined on a Kofler hot stage apparatus (Vienna, Austria) and are uncorrected. 1H-NMR spectra were recorded using a Bruker 400 spectrometer (Bruker, Rheinstatten, Germany), and chemical shifts are expressed as δ (ppm) with tetramethylsilane (TMS) as internal standard. The IR spectra were obtained on a Nicolet Magna FT-IR 550 spectrophotometer (potassium bromide disks).

General procedure for the synthesis of [1,3]dioxolo[4,5-g]chromen-8-one derivatives 4

3-(Benzo[d][1,3]dioxol-5-yloxy)propanoic acid 2 and 6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one 3 prepared according to [30] (Scheme 1).

Dry hydrogen chloride gas was passed through an ice-cold solution of 6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one 3 (0.5 mmol) and benzaldehyde derivative (0.7 mol) in absolute EtOH (3 mL) for 2 min. The reaction mixture was allowed to stand at room temperature for 48 h. The precipitated product was filtered off, dried, and recrystallized from ethanol and water.

7-Benzylidene-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4a)

Yield: 48%, mp 141–144°C. IR (KBr): 1664 (C = O) cm-1. 1H-NMR (CDCl3, 400 MHz) δ: 7.83 (s, 1H, benzylidene), 7.43 (s, 1H, H9), 7.42-7.25 (m, 5H, Ph), 6.41 (s, 1H, H4), 6.00 (s, 2H, H1, CH2), 5.29 (s, 2H, CH2). Anal. Calcd. for C17H12O4: C, 72.85; H, 4.32. Found: C, 72.68; H, 4.18.

7-(2-Methoxybenzylidene)-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4b)

Yield: 31%, mp 160–163°C. IR (KBr): 1660 (C = O) cm-1. 1H-NMR (CDCl3, 400 MHz) δ: 7.961 (s, 1H, benzylidene), 7.39 (s, 1H, H9), 7.04-6.94 (m, 4H, H3′, H4′, H5′, H6′), 6.40 (s, 1H, H4), 6.00 (s, 2H, H1, CH2), 5.17 (s, 2H, CH2), 3.86 (s, 3H, OCH3). Anal. Calcd. for C18H14O5: C, 69.67; H, 4.55. Found: C, 69.52; H, 4.41.

7-(3-Methoxybenzylidene)-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4c)

Yield: 42%, mp 161–163°C. IR (KBr): 1662 (C = O) cm-1. 1H-NMR (CDCl3, 400 MHz) δ: 7.79 (s, 1H, benzylidene), 7.38 (s, 1H, H9), 7.04-6.93 (m, 4H, H2′, H4′, H5′, H6′), 6.41(s, 1H, H4), 6.00 (s, 2H, H1, CH2), 5.29 (s, 2H, CH2), 3.84 (s, 3H, OCH3). Anal. Calcd. for C18H14O5: C, 69.67; H, 4.55. Found: C, 69.83; H, 4.72.

7-(4-Methoxybenzylidene)-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4d)

Yield: 31%, mp 169–172°C. IR (KBr): 1665 (C = O) cm-1. 1H-NMR (CDCl3, 400 MHz) δ: 7.79 (s, 1H, benzylidene), 7.38 (s, 1H, H9), 7.26 (d, J = 8.4 Hz, 2H, H, H), 6.96 (d, J = 8.4 Hz, 2H, H, H), 6.42 (s, 1H, H4), 6.00 (s, 2H, H1, CH2), 5.32 (s, 2H, CH2), 3.86 (s, 3H, OCH3). Anal. Calcd. for C18H14O5: C, 69.67; H, 4.55. Found: C, 69.53; H, 4.82.

7-(Benzo[d][1,3]dioxol-5-ylmethylene)-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4e)

Yield: 42%, mp 198–200°C. IR (KBr): 1667 (C = O) cm-1. 1H-NMR (CDCl3, 400 MHz) δ: 7.73 (s, 1H, benzylidene), 7.37 (s, 1H, H9), 6.86-6.67 (m, 3H, H3′, H4′, H6′), 6.41 (s, 1H, H4), 6.03 (s, 2H, H1′,CH2), 6.00 (s, 2H, H1, CH2), 5.29 (s, 2H, CH2). Anal. Calcd. for C18H12O6: C, 66.67; H, 3.73. Found: C, 66.48; H, 3.55.

Biological assay

Cell lines and cell culture

Human breast cancer cell lines including MDA-MB231, MCF-7 and T47D cells were obtained from the National Cell Bank of Iran, Pasteur Institute, Tehran, Iran. Cancer cell lines were grown in RPMI-1640 medium supplemented with 10% heat-inactivated fetal calf serum, 100 μg/ml streptomycin and 100 U/ml penicillin at 37°C in a humidified atmosphere with 5% CO2.

In vitro cytotoxicity assay

The in vitro cytotoxic activity of [1,3]dioxolo[4,5-g]chromen-8-ones 4a-e was achieved using MTT colorimetric assay. The in-vitro cytotoxic activity of all synthesized compounds were evaluated against three human breast cancer cell lines including MCF-7, T47D and MDA-MB-231 using MTT colorimetric assay according to the method of Mosman [31]. Cancer cell lines were grown in RPMI-1640 medium supplemented with 10% heat-inactivated fetal calf serum (Gibco BRL), 100 μg/ml streptomycin and 100 U/ml penicillin at 37°C in a humidified atmosphere with 5% CO2.

Briefly, cultures in the exponential growth phase were trypsinized and diluted in complete growth medium to give a total cell count of 5 × 104 cells/ml. 195 μl of the cell suspension was seeded into the wells of 96-well plates (Nunc, Denmark). The plates were incubated overnight in a humidified air atmosphere at 37°C with 5% CO2. After overnight incubation, 5 μl of the media containing various concentrations of the compounds was added per well in triplicate (final concentration 1, 5, 10 and 20 μg/ml). The plates were incubated for further 72 h. The final concentration of DMSO in the highest concentration of the applied compounds was 0.1%. In each plate, there were three control wells (cells without test compounds) and three blank wells (the medium with 0.1% DMSO) for cell viability. Etoposide and doxorubicine were used as positive controls for cytotoxicity. After treatment, the medium was removed and 200 μl phenol red-free medium containing MTT (1 mg/ml), was added to wells, followed by 4 h incubation. After incubation, the culture medium was then replaced with 100 μl of DMSO and the absorbance of each well was measured by using a microplate reader at 492 nm. For each compound, the concentration causing 50% cell growth inhibition (IC50) compared with the control was calculated from concentration response curves by regression analysis.

Fluorescence microscopy evaluation

Acridine orange/ethidium bromide (AO/EB) double staining [32] was applied to observe the morphological changes in cell death induced by the most potent compounds 4a and 4b. Acridine orange is taken up by both viable and dead cells and emitting green fluorescence if intercalated into double stranded nucleic acid (DNA) or red fluorescence if bound to single stranded nucleic acid (RNA) due to its accumulation in lysosomes. Ethidium bromide is taken up only by cells with an altered cell membrane and emits red fluorescence by intercalation into DNA. Cells were seeded in 6-well plates (4 × 105 cell/well) for 24 h. Then, cells were treated with IC50 concentration of test compounds for 24 h at 37°C with 5% CO2. After treatment, cells were washed twice with phosphate buffer saline (PBS) and then 1 μl of dye mixture (100 μg/ml AO and 100 μg/ml EB in PBS were mixed with 25 μl of cell suspension (0.4 × 106 cells/well) on a clean microscope slide. The suspension was immediately examined by Axoscope 2 plus fluorescence micro- scope from Zeiss (Germany) at 40× magnification.

Results and discussions

Benzo[d][1,3]dioxol-5-ol 1 (Scheme 1) was converted to 3-(benzo[d][1,3]dioxol-5-yloxy)propanoic acid 2 and subsequently to 6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one 3 according to the procedure [30]. In the next step, we investigated the reaction of 6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one 3 and 4-methoxybenzaldehyde to obtain the corresponding product, 7-(4-methoxybenzylidene)-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4d) (Table 1).
Table 1

Chemical structures and in vitro cytotoxic activity (IC 50 , μg/ml) a of compounds 4a-4e against breast cancer cell lines

Entry

Compound

MCF-7

T47D

MDA-MB-231

1

 

6.2 ± 0.1

4.6 ± 0.1

9.3 ± 2.1

2

 

> 100

5.7 ± 0.07

27.3 ± 7.1

3

 

> 100

18.8 ± 2.3

29.05 ± 1.7

4

 

> 100

9.2 ± 2.9

> 100

5

 

> 100

> 100

> 100

6

Doxorubicin

0.002 ± 0.002

0.03 ± 0.002

0.006 ± 0.004

7

Etoposide

7.5 ± 0.32

7.9 ± 0.45

11.9 ± 0.87

aThe IC50 values represent an average of three independent experiments (mean ± SD).

To run successful aldol condensation reaction, acid-catalyzed and base-catalyzed approaches were investigated using various conventional acids and base in different solvents. It was found that the aldol condensation was conducted in better yield in the presence of HCl (g).

Then, various derivatives including 7-(2-methoxybenzylidene)-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4b) and 7-(3-methoxybenzylidene)-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4c) possessing methoxy (OMe) group at ortho and meta positions were prepared to compare their bioactivities against the studied cell lines with that of the control. Also other two derivatives, 7-benzylidene-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4a) and 7-(benzo[d][1,3]dioxol-5-ylmethylene)-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4e) were prepared to investigate the effect of methxoy substituent on the cytotoxicity (Table 1).

The in vitro cytotoxic activity of [1,3]dioxolo[4,5-g]chromen-8-one derivatives 4, were tested against three human breast cancer cell lines including MCF-7, T47D, and MDA-MB-231. The 50% growth inhibitory concentration (IC50) for all derivatives were calculated and depicted in Table 1.

According to MTT assay results in Table 1, 7-benzylidene-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4a) showed the highest activity against MCF-7, T47D, and MDA-MB-231 cell lines with IC50 values of 6.2 ± 0.1, 4.6 ± 0.1, and 9.3 ± 2.1 μg/ml, respectively. In contrast, 7-(benzo[d][1,3]dioxol-5-ylmethylene)-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4e) did not show any cytotoxicity at the concentrations used. It seems that the presence of benzo[d][1,3]dioxole in benzylidene moiety decreases the cytotoxic activity of the corresponding compound. As can be seen in Table 1 (Entries 2–4), by introduction of OMe into the ortho, meta or para positions of benzylidenemoiety (compounds 4b, 4c, and 4d), different results were observed. All of them were inactive against MCF-7 cell line (IC50 > 100 μg/ml), whereas they exhibited good activity against T47D cell line with IC50 values of 5.7 ± 0.07, 18.8 ± 2.3, and 9.2 ± 2.9 μg/ml, respectively. It should be noted that compounds 4b and 4c were active against MDA-MB-231 cell line and 4d did not show any activity in this cell line. Presence of OMe in benzylidene moiety did not play crucial role on the improvement of cytotoxicity effects.

To study the effect of our synthetic compounds on cell lines, acridine orange/ethidium bromide double staining technique was used to evaluate the occurrence of apoptosis in cells. Analysis of the acridine orange/ethidium bromide staining results showed that 7-benzylidene-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4a) and 7-(2-methoxybenzylidene)-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4b) induced apoptosis in T47D cell line (Figure 2). The cells treated with the most potent compounds increased the extent of apoptosis relative to untreated control cells. As shown in Figure 2, the non-apoptotic control cells were stained green and the apoptotic cells had orange particles in their nuclei due to nuclear DNA fragmentation.
Figure 2

Morphological analysis of T47D cells treated with 4a and 4b by acridine orange/ethidium bromide double staining method. a) DMSO 1% as control, b) etoposide as positive control, c) cells treatedwith 4a for 24 h. d) cells treatedwith 4b for 24 h. White arrow indicates live cells, dashed arrow shows apoptotic cells. The images of cells were taken with a fluorescence microscope at 400 × magnification.

Conclusion

In conclusion, novel [1,3]dioxolo[4,5-g]chromen-8-one derivatives were synthesized and tested for their cytotoxic activity against three human breast cancer cell lines including MCF-7, T47D, and MDA-MB-231 using the MTT assay. 7-Benzylidene-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4a) showed the highest activity against the three studied cell lines. Also the analysis of acridine orange/ethidium bromide staining results revealed that the cytotoxic effect of 7-benzylidene-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4a) and 7-(2-methoxybenzylidene)-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4b) may be due to inducing apoptosis in cancer cell lines.

Declarations

Acknowledgements

The authors are thankful for financial support from the Research Council of Islamic Azad University and Iran National Elite Foundation (INEF).

Authors’ Affiliations

(1)
Department of Chemistry, Islamic Azad University
(2)
Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran
(3)
Biotechnology Department, Iranian Research Organization for Science and Technology
(4)
Drug Design and Development Research Center, Tehran University of Medicinal Sciences
(5)
Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences

References

  1. Hung TM, Thu CV, Dat NT, Ryoo SW, Lee JH, Kim JC, Na M, Jung HJ, Bae K, Min BS: Homoisoflavonoid derivatives from the roots of Ophiopogon japonicus and their in vitro anti-inflammation activity. Bioorg Med Chem Lett. 2010, 20: 2412-2416. 10.1016/j.bmcl.2010.03.043.View ArticlePubMedGoogle Scholar
  2. Siddaiah V, Maheswara M, Rao CV, Venkateswarlu S, Subbaraju GV: Synthesis, structural revision, and antioxidant activities of antimutagenic homoisoflavonoids from Hoffmanosseggiaintricata. Bioorg Med Chem Lett. 2007, 17: 1288-1290. 10.1016/j.bmcl.2006.12.008.View ArticlePubMedGoogle Scholar
  3. Perjési P, Das U, De Clercq E, Balzarini J, Kawase M, Sakagami H, Stables JP, Lorand T, Rozmer Z, Dimmock JR: Design, synthesis and antiproliferative activity of some 3-benzylidene-2,3-dihydro-1-benzopyran-4-ones which display selective toxicity for malignant cells. Eur J Med Chem. 2008, 43: 839-845. 10.1016/j.ejmech.2007.06.017.PubMed CentralView ArticlePubMedGoogle Scholar
  4. Al Nakib T, Bezjak V, Meegan MJ, Chandy R: Synthesis and antifungal activity of some 3-benzylidenechroman-4-ones, 3-benzylidenethiochroman-4-ones and 2-benzylidene-1-tetralones. Eur J Med Chem. 1990, 25: 455-462. 10.1016/0223-5234(90)90010-Z.View ArticleGoogle Scholar
  5. Tait S, Salvati AL, Desideri N, Fiore L: Antiviral activity of substituted homoisoflavonoids on enteroviruses. Antiviral Res. 2006, 72: 252-255. 10.1016/j.antiviral.2006.07.003.View ArticlePubMedGoogle Scholar
  6. Miadokova E, Masterova I, Vlckova V, Duhova V, Toth J: Antimutagenic potential of homoisoflavonoids from Muscari racemosum. J Ethnopharmacol. 2002, 81: 381-386. 10.1016/S0378-8741(02)00135-6.View ArticlePubMedGoogle Scholar
  7. Li N, Zhang JY, Zeng KW, Zhang L, Che YY, Tu PF: Anti-inflammatory homoisoflavonoids from the tuberous roots of Ophiopogon japonicus. Fitoterapia. 2012, 83: 1042-10455. 10.1016/j.fitote.2012.05.011.View ArticlePubMedGoogle Scholar
  8. Guo H, Zhao H, Kanno Y, Li W, Mu Y, Kuang X, Inouye Y, Koike K, Jiang H, Bai H: A dihydrochalcone and several homoisoflavonoids from Polygonatum odoratum are activators of adenosine monophosphate-activated protein kinase. Bioorg Med Chem Lett. 2013, 23: 3137-3139. 10.1016/j.bmcl.2013.04.027.View ArticlePubMedGoogle Scholar
  9. Bezabih M, Famuyiwa SO, Abegaz BM: HPLC analysis and NMR identification of homoisoflavonoids and stilbenoids from the inter-bulb surfaces of Scilla nervosa. Nat Prod Commun. 2009, 4: 1367-1370.PubMedGoogle Scholar
  10. Koorbanally C, Crouch NR, Langlois A, Du Toit K, Mulholland DA, Drewes SE: Homoisoflavanones and spirocyclic nortriterpenoids from three Eucomis species: E. comosa, E. schijffii and E. pallidiflora subsp. pole-evansii (Hyacinthaceae). S Afr J Bot. 2006, 72: 428-433. 10.1016/j.sajb.2005.12.006.View ArticleGoogle Scholar
  11. Urbancíková M, Masterová I, Tóth J: Estrogenic/antiestrogenic activity of homoisoflavonoids from bulbs of Muscari racemosum (L.) Miller. Fitoterapia. 2002, 73: 724-726. 10.1016/S0367-326X(02)00241-1.View ArticlePubMedGoogle Scholar
  12. Mutanyatta J, Matapa BG, Shushu DD, Abegaz BM: Homoisoflavonoids and xanthones from the tubers of wild and in vitro regenerated Ledebouria graminifolia and cytotoxic activities of some of the homoisoflavonoids. Phytochemistry. 2003, 62: 797-804. 10.1016/S0031-9422(02)00622-2.View ArticlePubMedGoogle Scholar
  13. Qi J, Xu D, Zhou YF, Qin MJ, Yu BY: New features on the fragmentation patterns of homoisoflavonoids in Ophiopogon japonicus by high-performance liquid chromatography/diode-array detection/electrospray ionization with multi-stage tandem mass spectrometry. Rapid Commun Mass Spectrum. 2010, 24: 2193-2206. 10.1002/rcm.4608.View ArticleGoogle Scholar
  14. Hsieh HK, Tsao LT, Wang JP, Lin CN: Synthesis and anti-inflammatory effect of chalcones. J Pharm Pharmacol. 2000, 52: 163-171. 10.1211/0022357001773814.View ArticlePubMedGoogle Scholar
  15. Domínguez JN, León C, Rodrigues J, de Domínguez NG, Gut J, Rosenthal PJ: Synthesis and evaluation of new antimalarial phenylurenylchalcone derivatives. J Med Chem. 2005, 48: 3654-3658. 10.1021/jm058208o.View ArticlePubMedGoogle Scholar
  16. Nielsen SF, Larsen M, Boesen T, Schønning K, Kromann H: Cationic chalcone antibiotics. design, synthesis, and mechanism of action. J Med Chem. 2005, 48: 2667-2677. 10.1021/jm049424k.View ArticlePubMedGoogle Scholar
  17. Qiao Z, Wang Q, Zhang F, Wang Z, Bowling T, Nare B, Jacobs RT, Zhang J, Ding D, Liu Y, Zhou H: Chalcone–Benzoxaborole hybrid molecules as potent antitrypanosomal agents. J Med Chem. 2012, 55: 3553-3557. 10.1021/jm2012408.View ArticlePubMedGoogle Scholar
  18. Lorenzo P, Alvarez R, Ortiz MA, Alvarez S, Piedrafita FJ, de Lera AR: Inhibition of IκB kinase-β and anticancer activities of novel chalcone adamantyl arotinoids. J MedChem. 2008, 51: 5431-5440.Google Scholar
  19. Desideri N, Bolasco A, Fioravanti R, Monaco LP, Orallo F, Yáñez M, Ortuso F, Alcaro S: Homoisoflavonoids: natural scaffolds with potent and selective monoamine oxidase-B inhibition properties. J Med Chem. 2011, 54: 2155-2164. 10.1021/jm1013709.View ArticlePubMedGoogle Scholar
  20. Foroumadi A, Samzadeh-Kermani A, Emami S, Dehghan G, Sorkhi M, Arabsorkhi F, Heidari MR, Abdollahi M, Shafiee A: Synthesis and antioxidant properties of substituted 3-benzylidene-7-alkoxychroman-4-ones. Bioorg Med Chem Lett. 2007, 17: 6764-6769. 10.1016/j.bmcl.2007.10.034.View ArticlePubMedGoogle Scholar
  21. Noushini S, Alipour E, Emami S, Safavi M, Ardestani SK, Gohari AR, Shafiee A, Foroumadi A: Synthesis and cytotoxic properties of novel (E)-3-benzylidene-7-methoxychroman-4-one derivatives. DARU J Pharm Sci. 2013, 21: 31-10.1186/2008-2231-21-31.View ArticleGoogle Scholar
  22. Shaikh MM, Kruger HG, Bodenstein J, Smith P, du Toit K: Anti-inflammatory activities of selected synthetic homoisoflavanones. Nat Prod Res. 2012, 26: 1473-1482. 10.1080/14786419.2011.565004.View ArticlePubMedGoogle Scholar
  23. Xu ZQ, Bucheit RW, Stup TL, Flavin MT, Khilevich A, Rezzo JD, Lin L, Zembower DE: In vitro anti-human immunodeficiency virus (HIV) activity of the chromanone derivative, 12-oxocalanolide A, a novel NNRTI. Bioorg Med Chem Lett. 1998, 8: 2179-2184. 10.1016/S0960-894X(98)00380-1.View ArticlePubMedGoogle Scholar
  24. Purushothaman KK, Kalyani K, Subramaniam K: Structure of bonducellin: a new homoisoflavonoids from Caesalpinia bonducella. India J Chem Sect B: Org Chem Incl Med Chem. 1982, 21: 383-386.Google Scholar
  25. Heller W, Andermatt P, Schaad WA, Tamm E: Homoisoflavonone IV. Neue inhaltsstoffe der eucomin-reihe von Eucomis bicolor. HelV Chim Acta. 1976, 59: 2048-2058. 10.1002/hlca.19760590618.View ArticlePubMedGoogle Scholar
  26. Yempala T, Sriram D, Yogeeswari P, Kantevari S: Molecular hybridization of bioactives: synthesis and antitubercular evaluation of novel dibenzofuran embodied homoisoflavonoids via Baylis–Hillman reaction. Bioorg Med ChemLett. 2012, 22: 7426-7430. 10.1016/j.bmcl.2012.10.056.View ArticleGoogle Scholar
  27. Lin LG, Xie H, Li HL, Tong LJ, Tang CP, Ke CQ, Liu QF, Lin LP, Geng MY, Jiang H, Zhao WM, Ding J, Ye Y: Naturally occurring homoisoflavonoids function as potent protein tyrosine kinase inhibitors by c-Src-based high-throughput screening. J Med Chem. 2008, 51: 4419-4429. 10.1021/jm701501x.View ArticlePubMedGoogle Scholar
  28. Nakhjiri M, Safavi M, Alipour E, Emami S, Atash AF, Jafari-Zavareh M, Ardestani SK, Khoshneviszadeh M, Foroumadi A, Shafiee A: Asymmetrical 2,6-bis(benzylidene)cyclohexanones: synthesis, cytotoxic activity and QSAR study. Eur J Med Chem. 2012, 50: 113-123.View ArticlePubMedGoogle Scholar
  29. Vosooghi M, Yahyavi H, Divsalar K, Shamsa H, Kheirollahi A, Safavi M, Ardestani SK, Sadeghi-Neshat S, Mohammadhosseini N, Edraki N, Khoshneviszadeh M, Shafiee A, Foroumadi A: Synthesis and In vitro cytotoxic activity evaluation of (E)-16-(substituted benzylidene) derivatives of dehydroepiandrosterone. DARU J Pharm Sci. 2013, 21: 34-10.1186/2008-2231-21-34.View ArticleGoogle Scholar
  30. Cueva JP, Giorgioni G, Grubbs RA, Chemel RB, Watts VJ, Nichols DE: Trans-2,3-Dihydroxy-6a,7,8,12b-tetrahydro-6H-chromeno[3,4-c]isoquinoline: synthesis, resolution, and preliminary pharmacological characterization of a new dopamine D1 receptor full agonist. J Med Chem. 2006, 49: 6848-6857. 10.1021/jm0604979.View ArticlePubMedGoogle Scholar
  31. Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983, 65: 55-63. 10.1016/0022-1759(83)90303-4.View ArticlePubMedGoogle Scholar
  32. Baskic D, Popovic S, Ristic P, Arsenijevic NN: Analysis of cycloheximide-induced apoptosis in human leukocytes: fluorescence microscopy using annexin V/propidium iodide versus acridin orange/ethidium bromide. Cell BiolInt. 2006, 30: 924-932.Google Scholar

Copyright

© Alipour et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Advertisement