Design and synthesis of coumarin-based organoselenium as a new hit for myeloprotection and synergistic therapeutic efficacy in adjuvant therapy

Abstract

A newly designed organoselenium compound, methyl substituted umbelliferone selenocyanate (MUS), was synthesized as a primary hit against the myelotoxic activity of carboplatin. MUS was administered at 6 mg/kg b.wt, p.o. in concomitant and pretreatment schedules with carboplatin (12 mg/kg b.wt, i.p. for 10 days) in female Swiss albino mouse. MUS treatment reduced (P < 0.001) the percentage of chromosomal aberrations, micronuclei formation, DNA damage and apoptosis in murine bone marrow cells and also enhanced (P < 0.001) the bone marrow cell proliferation of the carboplatin-treated mice. These activities cumulatively restored the viable bone marrow cell count towards normalcy. Myeloprotection by MUS was achieved, in part, due to a significant reduction in the ROS/RNS formation and restoration of glutathione redox pool. Additionally, MUS synergistically enhanced the cytotoxicity of carboplatin against two human cancer cell lines (MCF-7 and Colo-205). Furthermore, MUS can effectively potentiate the antitumour activity of carboplatin against two murine cancers (Dalton’s Lymphoma and Sarcoma-180) in vivo. These preclinical findings clearly indicate that MUS can improve the therapeutic index of carboplatin and ensures more effective therapeutic strategy against cancer for clinical development.

gem-Heterosubstituted (stannyl)methylsilanes as synthetic equivalents of functionalized α-stannyl(methyl) anions

“…Indeed, organoselenium derivatives represent a class of interesting and versatile compounds, finding a wide application both in organic synthesis [16][17][18][19] and in biology. [20][21][22] Table 1. Influence of the reaction conditions on the transfer of 1a-c onto aldehydes a Yield refers to both diastereoisomers.…”

Seleno‐L‐cystine and Vanillin Schiff's base: Synthesis, Reaction Mechanism and Biological activity

“…[20,21] The introduction of organoselenium moiety into other pharmacologically active scaffolds is today a recognizable concept for the creation of compounds with prominent medical application. This model has been successfully applied for the synthesis of organoselenium-modified steroids, [22] coumarins, [23] vitamins, [24] pyridines, [25] where the synergy between selenium functionality and other pharmacophore in one molecule is almost always leading to the establishment of improved biological activities and/or features necessary for the application under physiological conditions.…”

Chemoselective Preparation of New Families of Phenolic-Organoselenium Hybrids—A Biological Assessment

“…Selenium nanoparticles (SeNPs) are also gaining great attention as nano-sized drugs and drug delivery systems particularly effective against multidrug resistant tumours (MDR) [41]. Moreover, the use of organoselenium compounds has also been proven to be useful in adjuvant therapies [42], co-administered with a classical chemotherapeutic agent.…”