Selenium-Containing Chrysin and Quercetin Derivatives: Attractive Scaffolds for Cancer Therapy

Abstract

Selenium-containing chrysin (SeChry) and 3,7,3',4'-tetramethylquercetin (SePQue) derivatives were synthesized by a microwave-based methodology. In addition to their improvement in terms of DPPH scavenging and potential GPx-like activities, when tested in a panel of cancer cell lines both selenium-derivatives revealed consistently to be more cytotoxic when compared with their oxo and thio-analogues, evidencing the key role of selenocabonyl moiety for these activities. In particular, SeChry elicited a noteworthy cytotoxic activity with mean IC50 values 18- and 3-fold lower than those observed for chrysin and cisplatin, respectively. Additionally, these seleno-derivatives evidenced an ability to overcome cisplatin and multidrug resistance. Notably, a differential behavior toward malignant and nonmalignant cells was observed for SeChry and SePQue, exhibiting higher selectivity indexes when compared with the chalcogen-derivatives and cisplatin. Our preliminary investigation on the mechanism of cytotoxicity of SeChry and SePQue in MCF-7 human mammary cancer cells demonstrated their capacity to efficiently suppress the clonal expansion along with their ability to hamper TrxR activity leading to apoptotic cell death.

Emerging Utilization of Chrysin Using Nanoscale Modification

“…Selenium containing chrysin showed significant cytotoxicity with 18-fold lower IC 50 than that of chrysin. Moreover, the cytotoxic activity of selenium containing chrysin was superior to that of cisplatin, a commercial anticancer drug [74]. These results suggest that chrysin and other chemicals that have similar biological activity elicit increasing therapeutic efficacy with conjugation.…”

Synthesis and Antiproliferative Activity of Thioxoflavones Mannich Base Derivatives

“…The synthesis routes of the Mannich base derivatives 5a–f and 6a–f are illustrated in Scheme . Thioxoflavones 3 and 4 were effectively prepared by replacing the carbonyl to thio‐carbonyl on flavones 1 and 2 using Lawesson's reagent , respectively.…”

Selenophenes: Introducing a New Element into the Core of Non‐Steroidal Estrogen Receptor Ligands

“…[40] The key intermediates, 3a-d,f or the synthesis of 3,4-disubstituted selenophene derivatives 4a-d (Scheme 1B)w ere prepared by treating 3,4-dibromoselenophene 11 with aryl boronic acid by using Pd(OAc) 2 /PPh 3 instead of Pd(dppf)Cl 2 as the catalyst. The 3,4-dibromoselenophene intermediate (11) cannotb eo btained by bromination of selenophene, but it was synthesized by debromination of 2,3,4,5-tetrabromoselenophene (10)u sing Zn and AcOH in water. [41] 2,3,4,5-Tetrabromoselenophene (10)w as synthesizedb yb romination of selenophene using CHCl 3 and AcOH as solvent, with dropwise addition of Br 2 .…”

“…, Recently, the biological effects of organoselenium compounds have attracted much attention, as has their application as chiral catalysts . In particular, many diarylselenides possess anticancer, antiviral, antimicrobial, as well as antioxidant properties . In addition, a number of biologically active selenaheterocycles, such as cytoprotective agent ebselen, have recently been discovered .…”

“…[6][7][8] In particular,m any diarylselenides possess anticancer, antiviral,a ntimicrobial, as well as antioxidant properties. [9][10][11] In addition, an umber of biologically active selenaheterocycles, such as cytoprotective agent ebselen, have recently been dis-covered. [12] Moreover,w ea nd other found that af ew selenophene compoundsi nhibited the motilitya nd development of stageso ft he comparable nematode Haemonchus contortus.…”