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Breast cancer has the highest incidence rate among all malignancies worldwide. Its high mortality is mainly related to the occurrence of multidrug resistance, which significantly limits therapeutic options. In this regard, there is an urgent need to develop compounds that would overcome this phenomenon. There are few reports in the literature that selenium compounds can modulate the activity of P-glycoprotein (MDR1). Therefore, we performed in silico studies and evaluated the effects of the novel selenoesters EDAG-1 and EDAG-8 on BCRP, MDR1, and MRP1 resistance proteins in MCF-7 and MDA-MB-231 breast cancer cells. The cytometric analysis showed that the tested compounds (especially EDAG-8) are inhibitors of BCRP, MDR1, and MRP1 efflux pumps (more potent than the reference compounds—novobiocin, verapamil, and MK-571). An in silico study correlates with these results, suggesting that the compound with the lowest binding energy to these transporters (EDAG-8) has a more favorable spatial structure affecting its anticancer activity, making it a promising candidate in the development of a novel anticancer agent for future breast cancer therapy. [ABSTRACT FROM AUTHOR]

Breast cancer is a major malignancy among women, characterized by a high mortality rate. The available literature evidence indicates that selenium, as a trace element, has chemopreventive properties against many types of cancer; as such, compounds containing it in their structure may potentially exhibit anticancer activity. Accordingly, we have undertaken a study to evaluate the effects of novel selenoesters (EDAG-1, -7, -8, -10) on MCF-7 and MDA-MB-231 breast cancer cells. Our analysis included investigations of cell proliferation and viability as well as cytometric determinations of apoptosis/autophagy induction, changes in mitochondrial membrane polarity (ΔΨm), caspase 3/7, 8, and 9 activities, and Bax, Bcl-2, p53, Akt, AMPK, and LC3A/B proteins. The obtained data revealed that the tested derivatives are highly cytotoxic and inhibit cell proliferation even at nanomolar doses (0.41–0.79 µM). Importantly, their strong proapoptotic properties (↑ caspase 3/7) are attributable to the effects on both the extrinsic (↑ caspase 8) and intrinsic (↓ ΔΨm and Bcl-2, ↑ Bax, p53, and caspase 9) pathways of apoptosis. Moreover, the tested compounds are autophagy activators (↓ Akt, ↑ autophagosomes and autolysosomes, AMPK, LC3A/B). In summary, the potent anticancer activity suggests that the tested compounds may be promising drug candidates for future breast cancer therapy. [ABSTRACT FROM AUTHOR]

An unprecedented regiodivergent palladium‐catalyzed carbonylation of aromatic alkenes has been developed. Utilizing commercially available Pd(CH3CN)2Cl2 in the presence of 1,1′‐ferrocenediyl‐bis(tert‐butyl(pyridin‐2‐yl)phosphine) ligand L8 diverse selenoesters are obtained in a straightforward manner. Key to success for the control of the regioselectivity of the carbonylation step is the concentration of the acidic co‐catalyst. This general protocol features wide functional group compatibility and good regioselectivity. Mechanistic studies suggest that the presence of stoichiometric amounts of acid changes the properties and coordination mode of the ligand leading to reversed regioselectivity. [ABSTRACT FROM AUTHOR]

An unprecedented regiodivergent palladium‐catalyzed carbonylation of aromatic alkenes has been developed. Utilizing commercially available Pd(CH3CN)2Cl2 in the presence of 1,1′‐ferrocenediyl‐bis(tert‐butyl(pyridin‐2‐yl)phosphine) ligand L8 diverse selenoesters are obtained in a straightforward manner. Key to success for the control of the regioselectivity of the carbonylation step is the concentration of the acidic co‐catalyst. This general protocol features wide functional group compatibility and good regioselectivity. Mechanistic studies suggest that the presence of stoichiometric amounts of acid changes the properties and coordination mode of the ligand leading to reversed regioselectivity. [ABSTRACT FROM AUTHOR]

Herein, we report a new and efficient method for the synthesis of selenoesters by a direct coupling reaction of alkyl selenides with acyl chlorides in ethanol under transition metal‐free conditions. This nucleophilic acyl substitution afforded selenoesters in good yields. Traditionally, synthesis of selenoesters involve the reaction of acyl chlorides with an organoselenium anions generated in situ through the reductive cleavage of previously prepared diselenides. Our one‐pot approach avoids the pre‐preparation of diselenides and operated in atom‐economical and environmentally friendly conditions. The synthetic utility of these selenoesters was studied using Se‐butyl benzoselenoate as substrate in a Sonogashira‐type cross‐coupling reaction. [ABSTRACT FROM AUTHOR]

Recently, selenium containing derivatives have attracted more attention in medicinal chemistry. In the present work, the anticancer activity of symmetrical selenoesters was investigated by studying the reversal of efflux pump-related and apoptosis resistance in sensitive and resistant human colon adenocarcinoma cells expressing the ABCB1 protein. The combined effect of the compounds with doxorubicin was demonstrated with a checkerboard assay. The ABCB1 inhibitory and the apoptosis-inducing effects of the derivatives were measured with flow cytometry. Whole transcriptome sequencing was carried out on Illumina platform upon the treatment of resistant cells with the most potent derivatives. One ketone and three methyl ester selenoesters showed synergistic or weak synergistic interaction with doxorubicin, respectively. Ketone selenoesters were the most potent ABCB1 inhibitors and apoptosis inducers. Nitrile selenoesters could induce moderate early and late apoptotic processes that could be explained by their ABCB1 modulating properties. The transcriptome analysis revealed that symmetrical selenoesters may influence the redox state of the cells and interfere with metastasis formation. It can be assumed that these symmetrical selenocompounds possess toxic, DNA-damaging effects due to the presence of two selenium atoms in the molecule, which may be augmented by the presence of symmetrical groups. [ABSTRACT FROM AUTHOR]

Lipase‐catalyzed enantioselective synthetic reactions employing enol esters, activated esters, anhydrides, and oximes as acyl donors is a well‐consolidated strategy towards enantiopure compounds. However, lipases can also cleave the C−S bond of thioesters, proving that other classes of substances can be used as acyl donors in lipase‐catalyzed transformations. Herein we describe the application of selenoesters as a new class of acyl donors in enzymatic kinetic resolution of chiral alcohols. A series of selenoesters was successfully employed in the resolution of chiral primary and secondary alcohols, demonstrating that lipases can also cleave the C−Se bond. Assays using selenoesters as acyl donors in lipase‐catalyzed reactions furnished enantiopure compounds (e.e.>99 %) and enantiomeric ratio (E>200). We also observed that the enzymatic reaction is accelerated in an oxygen atmosphere and performing a preparative scale reaction could demonstrate how simple and easy the purification process is to recover the diselenide formed during the resolution. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer ranks at the forefront of all malignancies worldwide, and the numerous incidences and mortality rate associated with it are very burdensome to the health care system. Consequently, there is a constant need for new effective drugs with anticancer activity. There have been reports of highly cytotoxic effects of selenium compounds against cancer cells for some time. Hence, our team decided to evaluate the anticancer activity of novel selenoesters in MCF-7 and MDA-MB-231 breast cancer cells. Our results reveal that these compounds are cytotoxic at very low micromolar concentrations, which is associated with the induction of apoptosis and autophagy and arrest of breast cancer cells in the S or G2/M phase of the cell cycle. The obtained results are promising and show that selenium-containing compounds are worth more attention, as they show considerable potential for future candidates as anticancer agents. Disturbing cancer statistics, especially for breast cancer, are becoming a rationale for the development of new anticancer therapies. For the past several years, studies have been proving a greater role of selenium in the chemoprevention of many cancers than previously considered; hence, a trend to develop compounds containing this element as potential agents with anticancer activity has been set for some time. Therefore, our study aimed to evaluate the anticancer activity of novel selenoesters (EDA-71, E-NS-4) in MCF-7 and MDA-MB-231 human breast cancer cells. The assays evaluating proliferation and cell viability, and flow cytometer analysis of apoptosis/autophagy induction, changes in mitochondrial membrane potential, disruption of cell cycle phases, and protein activity of mTOR, NF-κB, cyclin E1/A2, and caspases 3/7, 8, 9, 10 were performed. The obtained results indicate that the tested selenoesters are highly cytotoxic and exhibit antiproliferative activity at low micromolar doses (<5 µM) compared with cisplatin. The most active compound—EDA-71—highly induces apoptosis, which proceeds via both pathways, as evidenced by the activation of all tested caspases. Furthermore, we observed the occurrence of autophagy (↓ mTOR levels) and cell cycle arrest in the S or G2/M phase (↓ cyclin E1, ↑ cyclin A2). [ABSTRACT FROM AUTHOR]

Eco-friendly nano-cerium oxide was synthesized via a simple and efficient solution combustion route using novel aqueous Brahma Kamal leaf extract and characterized by several techniques including powder x-ray diffraction, Fourier transform infrared spectroscopy, photoluminescence, ultraviolet visible spectroscopy, energy-dispersive x-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The nanomaterial exhibited an excellent catalytic activity in the synthesis of selenoesters of amino acids through the reaction of corresponding amino acyl chloride derivatives with the in situ-generated NaHSe, followed by addition of α-bromo esters. Wide ranges of unsymmetrical selenoester derivatives of amino acids were afforded with good to excellent yields, and the structures were characterized by high-resolution mass spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopy, and Fourier transform infrared spectroscopy techniques. Furthermore, nano-CeO2 exhibits tremendous catalytic activity in the production of biodiesel from Annona squamosa oil and achieved around 89% biodiesel yield. The biodiesel produced satisfies ASTM standards. [ABSTRACT FROM AUTHOR]

Selenoesters are compounds of great synthetic relevance since they can be used in several types of chemical transformations and mainly due to their great capacity in the formation of acyl radicals. Therefore, the scientific community has been developing several methods for the synthesis of this class of molecules. This review will address the synthesis of these compounds from different starting materials, such as carboxylic acids derivatives (acid chlorides and anhydrides), aldehydes, selenoacetylenes and miscellaneous methods. [ABSTRACT FROM AUTHOR]

Prior studies have reported the potent and selective cytotoxic, pro-apoptotic, and chemopreventive activities of a cyclic selenoanhydride and of a series of selenoesters. Some of these selenium derivatives demonstrated multidrug resistance (MDR)-reversing activity in different resistant cancer cell lines. Thus, the aim of this study was to evaluate the pharmaceutical and safety profiles of these selected selenocompounds using alternative methods in silico and in vitro. One of the main tasks of this work was to determine both the physicochemical properties and metabolic stability of these selenoesters. The obtained results proved that these tested selenocompounds could become potential candidates for novel and safe anticancer drugs with good ADMET parameters. The most favorable selenocompounds turned out to be the phthalic selenoanhydride (EDA-A6), two ketone-containing selenoesters with a 4-chlorophenyl moiety (EDA-71 and EDA-73), and a symmetrical selenodiester with a pyridine ring and two selenium atoms (EDA-119). [ABSTRACT FROM AUTHOR]

Lithium, sodium, and potassium ferrocenecarboselenoates were synthesized in good yields by the reaction of ferrocenoyl chloride with the corresponding metal selenides. In air, the saltsquickly oxidized to give diferrocenoyl diselenide. The salts readily reacted with alkyl and organo-germanium, -tin and -lead halides to give the corresponding Se-alkyl and Se-organo Group-14 element ferrocenecarboselenoates [(FcCOSe) xMPh4- x ( M = Ge, Sn, Pb; x = 1-3) in moderate to good yields. In contrast, the reaction of the sodium and potassium salts with trimethylsilyl chloride led to O-trimethylsilyl ferrocenecarboselenoate FcCSeOSiMe3. Treatment of the O-silyl ester with RbF and CsF led to rubidium and cesium ferrocenecarboselenoates, respectively, in good yields. The structures of FcCOSe tBu, (FcCOSe)2SnPh2, and FcCOSePbPh3 were revealed by X-ray molecular structure analysis. [ABSTRACT FROM AUTHOR]

Keywords: acyl radicals; diselenides; selanyl esters; selenoesters; selenol esters EN acyl radicals diselenides selanyl esters selenoesters selenol esters 1 1 1 06/18/21 20210616 NES 210616 B The galaxy of conjugated molecular nanotubes b : how much more remains to be discovered? For more details see the Minireview by R. Hernández Sánchez et al. on 8642 ff. GLO:OLD/16jun21:chem202183462-toc-0001.jpg PHOTO (COLOR): . gl GLO:OLD/16jun21:chem202183462-toc-0001.jpg PHOTO (COLOR): . gl Acyl radicals, diselenides, selanyl esters, selenoesters, selenol esters. [Extracted from the article]

The synthesis of these compounds is addressed from different starting materials, such as carboxylic acids derivatives (acid chlorides and anhydrides), aldehydes, selenoacetylenes and miscellaneous methods. Acyl radicals, diselenides, selanyl esters, selenoesters, selenol esters Keywords: acyl radicals; diselenides; selanyl esters; selenoesters; selenol esters EN acyl radicals diselenides selanyl esters selenoesters selenol esters 1 1 1 06/18/21 20210616 NES 210616 B Selenoesters are compounds of great synthetic relevance b , since they can be used in several chemical transformations and mainly due to their great capacity in the formation of acyl radicals. [Extracted from the article]

The emergence of drug-resistant pathogens leads to a gradual decline in the efficacy of many antibacterial agents, which poses a serious problem for proper therapy. Multidrug resistance (MDR) mechanisms allow resistant bacteria to have limited uptake of drugs, modification of their target molecules, drug inactivation, or release of the drug into the extracellular space by efflux pumps (EPs). In previous studies, selenoesters have proved to be promising derivatives with a noteworthy antimicrobial activity. On the basis of these results, two series of novel selenoesters were synthesized to achieve more potent antibacterial activity on Gram-positive and Gram-negative bacteria. Fifteen selenoesters (eight ketone-selenoesters and seven cyano-selenoesters) were investigated with regards to their efflux pump-inhibiting, anti-quorum-sensing (QS), and anti-biofilm effects in vitro. According to the results of the antibacterial activity, the ketone-selenoesters proved to be more potent antibacterial compounds than the cyano-selenoesters. With regard to efflux pump inhibition, one cyano-selenoester on methicillin-resistant S. aureus and one ketone-selenoester on Salmonella Typhimurium were potent inhibitors. The biofilm inhibitory capacity and the ability of the derivatives to disrupt mature biofilms were noteworthy in all the experimental systems applied. Regarding QS inhibition, four ketone-selenoesters and three cyano-selenoesters exerted a noteworthy effect on Vibrio campbellii strains. [ABSTRACT FROM AUTHOR]

Selenoesters and the selenium isostere of phthalic anhydride are bioactive selenium compounds with a reported promising activity in cancer, both due to their cytotoxicity and capacity to reverse multidrug resistance. Herein we evaluate the antiviral, the biofilm inhibitory, the antibacterial and the antifungal activities of these compounds. The selenoanhydride and 7 out of the 10 selenoesters were especially potent antiviral agents in Vero cells infected with herpes simplex virus-2 (HSV-2). In addition, the tested selenium derivatives showed interesting antibiofilm activity against Staphylococcus aureus and Salmonella enterica serovar Typhimurium, as well as a moderate antifungal activity in resistant strains of Candida spp. They were inactive against anaerobes, which may indicate that the mechanism of action of these derivatives depends on the presence of oxygen. The capacity to inhibit the bacterial biofilm can be of particular interest in the treatment of nosocomial infections and in the coating of surfaces of prostheses. Finally, the potent antiviral activity observed converts these selenium derivatives into promising antiviral agents with potential medical applications. [ABSTRACT FROM AUTHOR]

Bacterial multidrug resistance is becoming a growing problem for public health, due to the development and spreading of bacterial strains resistant to antimicrobials. In this study, the antibacterial and multidrug resistance reversing activity of a series of seleno-carbonyl compounds has been evaluated. The effects of eleven selenocompounds on bacterial growth were evaluated in Staphylococcus aureus, methicillin resistant S. aureus (MRSA), Enterococcus faecalis, Escherichia coli, and Chlamydia trachomatis D. The combination effect of compounds with antibiotics was examined by the minimum inhibitory concentration reduction assay. Their efflux pump (EP) inhibitory properties were assessed using real-time fluorimetry. Relative expressions of EP and quorum-sensing genes were studied by quantitative PCR. Results showed that a methylketone selenoester had remarkable antibacterial activity against Gram-positive bacteria and potentiated the activity of oxacillin in MRSA. Most of the selenocompounds showed significant anti-chlamydial effects. The selenoanhydride and the diselenodiester were active inhibitors of the AcrAB-TolC system. Based on these results it can be concluded that this group of selenocompounds can be attractive potential antibacterials and EP inhibitors. The discovery of new derivatives with a significant antibacterial activity as novel selenocompounds, is of high impact in the fight against resistant pathogens. [ABSTRACT FROM AUTHOR]