RESUMEN
A series of phenyl ß-carbonyl selenides with o-ester functionality substituted on the oxygen atom with chiral and achiral alkyl groups was synthesized. All compounds are the first examples of this type of organoselenium derivatives with an ester substituent in the ortho position. The obtained derivatives were tested as antioxidants and anticancer agents to see the influence of an ester functionality on the bioactivity of ß-carbonyl selenides by replacing the o-amide group with an o-ester group. The best results as an antioxidant agent were observed for O-((1R,2S,5R)-(-)-2-isopropyl-5-methylcyclohexyl)-2-((2-oxopropyl)selanyl)benzoate. The most cytotoxic derivative against breast cancer MCF-7 cell lines was O-(methyl)-2-((2-oxopropyl)selanyl)benzoate and against human promyelocytic leukemia HL-60 was O-(2-pentyl)-2-((2-oxopropyl)selanyl)benzoate.
Asunto(s)
Antineoplásicos , Antioxidantes , Ésteres , Compuestos de Organoselenio , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/síntesis química , Ésteres/química , Ésteres/farmacología , Ésteres/síntesis química , Compuestos de Organoselenio/química , Compuestos de Organoselenio/farmacología , Compuestos de Organoselenio/síntesis química , Células MCF-7 , Células HL-60 , Relación Estructura-Actividad , Estructura MolecularRESUMEN
A series of unsymmetrical phenyl ß-carbonyl selenides with o-amido function substituted on the nitrogen atom with chiral alkyl groups was obtained. The compounds form a series of enantiomeric and diastereomeric pairs and present the first examples of this type of chiral Se derivatives. All obtained selenides were further evaluated as antioxidants and anticancer agents to define the influence of the particular stereochemistry of the attached functional groups on the bioactivity of the molecules. The highest H2O2 reduction potential was observed for N-(cis-2-hydroxy-1-indanyl)-2-((2-oxopropyl)selanyl)benzamide, and the best radical scavenging properties for N-(-1-hydroxy-2-butanyl)-2-((2-oxopropyl)selanyl)benzamide. Also, both enantiomers of the N-(1-hydroxy-2-butanyl) selenide expressed the highest cytotoxic potential towards human promyelocytic leukemia HL-60 cell line with similar IC50 values 14.4 ± 0.5 and 16.2 ± 1.1 µM, respectively. On the other hand, breast cancer cell line MCF-7 was most sensitive to N-((R)-(-)-1-hydroxy-2-butanyl)- 2-((2-oxopropyl)selanyl)benzamide (IC50 of 35.7 ± 0.6 µM). The structure-activity dependence of the obtained Se derivatives was discussed, and the most potent compounds were selected.
RESUMEN
Organoselenium compounds are well-known for their numerous biocapacities, which result from the uniqueness of the selenium atom and the possibility of constructing heterorganic molecules that can mimic the activity of selenoenzymes, crucial for a multitude of important physiological processes. In this paper, we have synthesized a series of N-substituted benzisoselenazolones and corresponding diphenyl diselenides possessing lipophilic long carbon chains, solely or with additional polar insets: phenyl linkers and ester groups. Evaluation of their antioxidant and cytotoxic activity revealed an increased H2O2-reduction potential of diphenyl diselenides bearing N-octyl, ethyl N-(12-dodecanoate)- and N-(8-octanoate) groups, elevated radical scavenging activity of 2,2'-diselenobis(N-dodecylbenzamide) and a promising cytotoxic potential of N-(4-dodecyl)phenylbenzisoselenazol-3(2H)-one.
RESUMEN
In the present work, a series of N-terpenyl organoselenium compounds (CHB1-6) were evaluated for antimycotic activity by determining the minimum inhibitory concentration (MIC) for each compound in fluconazole (FLU)-sensitive (S1) and FLU-resistant (S2) strains of Candida albicans (C. albicans). The most active compounds in the MIC screen were CHB4 and CHB6, which were then evaluated for cytotoxicity in human cervical cancer cells (KB-3-1) and found to be selective for fungi. Next, CHB4 and CHB6 were investigated for skin irritation using a reconstructed 3D human epidermis and both compounds were considered safe to the epidermis. Using a mouse model of vulvovaginal candidiasis (VVC), CHB4 and CHB6 both exhibited antimycotic efficacy by reducing yeast colonization of the vaginal tract, alleviating injury to the vaginal mucosa, and decreasing the abundance of myeloperoxidase (MPO) expression in the tissue, indicating a reduced inflammatory response. In conclusion, CHB4 and CHB6 demonstrate antifungal activity in vitro and in the mouse model of VVC and represent two new promising antifungal agents.
Asunto(s)
Candidiasis Vulvovaginal , Femenino , Humanos , Candidiasis Vulvovaginal/tratamiento farmacológico , Candidiasis Vulvovaginal/metabolismo , Candidiasis Vulvovaginal/microbiología , Antifúngicos/metabolismo , Fluconazol/farmacología , Candida albicans , Vagina/microbiología , Pruebas de Sensibilidad MicrobianaRESUMEN
This publication presents the results of work on the development of a quick and cheap electrochemical immunosensor for the diagnosis of infections with the pathogen Streptococcus agalactiae. The research was carried out on the basis of the modification of the well-known glassy carbon (GC) electrodes. The surface of the GC (glassy carbon) electrode was covered with a film made of nanodiamonds, which increased the number of sites for the attachment of anti-Streptococcus agalactiae antibodies. The GC surface was activated with EDC/NHS (1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-Hydroxysuccinimide). Determination of electrode characteristics after each modification step, performed using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS).
RESUMEN
Organoselenium compounds are well-known for their unique biological properties, including antioxidant, anticancer and anti-inflammatory. They result from the presence of a particular Se-moiety enclosed in a structure that provides physicochemical features necessary for effective drug-target interactions. Looking for a proper drug design that considers the influence of each structural element has to be conducted. In this paper, we have synthesized a series of chiral phenylselenides, possessing an additional N-substituted amide moiety, and evaluated their antioxidant and anticancer potential. The presented derivatives, as a group of enantiomeric and diastereomeric pairs, enabled a thorough investigation of the 3D structure-activity dependence in correlation with the presence of the phenylselanyl group as the potential pharmacophore. The N-indanyl derivatives possessing a cis- and trans-2-hydroxy group were selected as the most promising antioxidants and anticancer agents.
RESUMEN
The ability of organoselenium molecules to mimic the activity of the antioxidant selenoenzyme glutathione peroxidase (GPx) allows for their use as antioxidant or prooxidant modulators in several diseases associated with the disruption of the cell redox homeostasis. Current drug design in the field is partially based on specific modifications of the known Se-therapeutics aimed at achieving more selective bioactivity towards particular drug targets, accompanied by low toxicity as the therapeutic window for organoselenium compounds tends to be very narrow. Herein, we present a new group of Se-based antioxidants, structurally derived from the well-known group of GPx mimics-benzisoselenazol-3(2H)-ones. A series of N-substituted unsymmetrical phenylselenides with an o-amido function has been obtained by a newly developed procedure: a copper-catalyzed nucleophilic substitution by a Se-reagent formed in situ from diphenyl diselenide and sodium borohydride. All derivatives were tested as antioxidants and anticancer agents towards breast (MCF-7) and leukemia (HL-60) cancer cell lines. The highest H2O2-scavenging potential was observed for N-(3-methylbutyl)-2-(phenylselanyl)benzamide. The best antiproliferative activity was found for (-)-N-(1S,2R,4R)-menthyl-2-(phenylselanyl)benzamide (HL-60) and ((-)-N-(1S,2R,3S,6R)-(2-caranyl))benzamide (MCF-7). The structure-activity correlations, including the differences in reactivity of the obtained phenyl selenides and corresponding benzisoselenazol-3(2H)-ones, were performed.