Assessment of Immunomodulatory Activities and<i>in vitro</i>Toxicity of New Quinolone 7-ethyl 9-ethyl-6-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-<i>h</i>]quinoline-7-carboxylate

Berberine is a bioactive isoquinoline alkaloid derived from many plants. Although berberine has been shown to inhibit growth and induce apoptosis of several tumor cell lines, its poor absorption and moderate activity hamper its full therapeutic potential. Here, we describe the synthesis of a series of 9-O-substituted berberine derivatives with improved antiproliferative and apoptosis-inducing activities. An analysis of novel berberine derivatives by EPR spectroscopy confirmed their similar photosensitivity and analogous behavior upon UVA irradiation as berberine, supporting their potential to generate ROS. Improved antitumor activity of novel berberine derivatives was revealed by MTT assay, by flow cytometry and by detection of apoptotic DNA fragmentation and caspase-3 activation, respectively. We showed that novel berberine derivatives are potent inhibitors of growth of HeLa and HL-60 tumor cell lines with IC50 values ranging from 0.7 to 16.7 µM for HL-60 cells and 36 to >200 µM for HeLa cells after 48 h treatment. Further cell cycle analysis showed that the observed inhibition of growth of HL-60 cells treated with berberine derivatives was due to arresting these cells in the G2/M and S phases. Most strikingly, we found that berberine derivative 3 (9-(3-bromopropoxy)-10-methoxy-5,6-dihydro-[1,3]dioxolo[4,5-g]isoquino[3,2-a] isoquinolin-7-ylium bromide) possesses 30-fold superior antiproliferative activity with an IC50 value of 0.7 µM and 6-fold higher apoptosis-inducing activity in HL-60 leukemia cells compared to berberine. Therefore, further studies are merited of the antitumor activity in leukemia cells of this berberine derivative.

show abstract

“…The morphology of cells treated with tested drugs was evaluated using light microscopy (Zeiss Jenalumar, Jena, Germany) [65].…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Anticancer Activity of Novel 9-O-Substituted Berberine Derivatives

Milata

Svedova

Barbieriková

et al. 2019

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…A 1,2,5-selenadiazole derived quinolone ( VIII-60 in Figure ) presented good antiproliferative activity in HeLa cells through apoptosis induction, which improved when irradiated with ultraviolet A (UVA) light . The same compound also exhibited high antiproliferative activity in leukemia cells and immunomodulatory effect on murine cell lines …”

Section: 25-selenadiazolesmentioning

confidence: 99%

“…138 The same compound also exhibited high antiproliferative activity in leukemia cells and immunomodulatory effect on murine cell lines. 139 In addition to their application in cancer, 1,2,5-selenadiazoles have shown application in other emerging fields, e.g., in semiconducting polymer dots (Pdots) used for fluorescent probes in biology and medicine. Pdots have been derivatized with 1,2,5-selenadiazole motif (IX-61 in Figure 9), achieving an improved sensitivity for ratiometric detection of hypo-chlorous acid in vivo, 140 an endogenous ROS linked to the progression of many human diseases.…”

Section: 24-selenadiazolesmentioning

confidence: 99%

Development and Therapeutic Potential of Selenazo Compounds

et al. 2019

View full text Add to dashboard Cite

Incorporation of selenium (Se) atom into small molecules can substantially enhance their antioxidant, antiinflammatory, antimutagenic, antitumoral or chemopreventive, antiviral, antibacterial, antifungal, antiparasitic, and neuroprotective effects. Specifically, selenazo compounds have received great attention owing to their chemical properties, pharmaceutical applications, and low toxicity. In this Perspective, we compile extensive literature evidence with the description and discussion of the most recent advances in different selenazo and selenadiazo motifs as potential pharmacological candidates. We also provide some perspectives on the challenges and future directions in the advancement of these selenazo compounds, each of which could generate drug candidates for various diseases.

show abstract

“…Selenium-containing organic molecules exhibit a wide spectrum of medicinal properties, such as antiviral, antihypertensive, antioxidant, antimicrobial, and antitumor properties . In addition to these, organoselenium compounds are used as enzyme inhibitors, cytokine inducers, immune modulators, and stimulators for catalytic functions of several enzymes. , Organic selenocyanates have been studied for anticancer properties . Apart from their pharmaceutical importance, organoselenium compounds are also very useful as intermediates as well as in catalysis .…”

Section: Introductionmentioning

confidence: 99%

“… 1 In addition to these, organoselenium compounds are used as enzyme inhibitors, cytokine inducers, immune modulators, and stimulators for catalytic functions of several enzymes. 1 , 2 Organic selenocyanates have been studied for anticancer properties. 3 Apart from their pharmaceutical importance, organoselenium compounds are also very useful as intermediates as well as in catalysis.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Selenocyanates and Selenoethers of Amino Pyrazoles and Amino Uracils by In Situ Triselenium Dicyanide from Malononitrile and Selenium Dioxide

Ali,

Mondal,

Panday

et al. 2023

ACS Omega

View full text Add to dashboard Cite

Herein, we report an efficient method for synthesis of novel selenocyanates of amino pyrazole, amino uracil, and amino isoxazole derivatives using in situ triselenium dicyanide from the combination of malononitrile and selenium dioxide in DMSO medium. Using the same combination but changing the stoichiometry of reagents and sequence of addition and temperature, symmetrical selenoethers of amino pyrazoles and amino uracils were prepared in good yields. Furthermore, selenocyanates of amino pyrazoles were utilized for the synthesis of corresponding alkynyl selenides in the presence of CuI and Cs2CO3. The salient features of this methodology are inexpensive starting materials, short reaction time, and good to very good yields. This method is also applicable for the gram-scale synthesis of selenocyanates of amino pyrazoles and amino uracils.

show abstract

Assessment of Immunomodulatory Activities andin vitroToxicity of New Quinolone 7-ethyl 9-ethyl-6-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-h]quinoline-7-carboxylate

Abstract: DMEM, Dulbecco's modified eagle medium; DMSO, Dimethylsulfoxide; EtBr, Ethidium bromide; PI, Propidium iodide; E2h, 7-ethyl 9-ethyl-6-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-h]quinoline-7-carboxylate.

Cited by 11 publications

References 58 publications

Synthesis and Anticancer Activity of Novel 9-O-Substituted Berberine Derivatives

Synthesis and Anticancer Activity of Novel 9-O-Substituted Berberine Derivatives

Development and Therapeutic Potential of Selenazo Compounds

Synthesis of Selenocyanates and Selenoethers of Amino Pyrazoles and Amino Uracils by In Situ Triselenium Dicyanide from Malononitrile and Selenium Dioxide

Contact Info

Product

Resources

About