Nowadays, selective estrogen receptor modulators (SERMs) and downregulators (SERDs) are used as the first‐line medical treatment for estrogen receptor positive (ER+) tumors. Herein we report synthesis, ER‐α binding activity, and cytotoxicity of LSZ102 selenium analogues 11 and 28. TR‐FRET competitive ER‐α binding experiments and cytotoxicity assays have shown that the selenium analogues exhibit closely related activity to LSZ102. Furthermore, the prepared selenium analogues are not toxic in rat cardiomyoblasts (H9C2), indicating that substituted benzo[b]selenophene is a prospective scaffold for the development of ER‐α modulators and downregulators for the treatment of ER+ cancers.

We report the design and synthesis of 7 novel benzoselenophenes, and their ER-α binding activity and cytotoxicity. Compound 21b is a considerably more effective ER-α binder (IC 50 = 0.44 nM) than the widely known SERM drug raloxifene (IC 50 = 1.78 nM).

Arguably, the simplest way for the preparation of benzo[b]tellurophenes has been elaborated. Cyclization of o-haloarylalkynes in the presence of Te-NaOH-DMSO triad occurs by simple mixing of starting materials and heating overnight without the need for dry and inert atmosphere and provides the corresponding benzo[b]tellurophenes in up to 90 % GC-yield. Catalytic telluration of aryl iodide substrates extends the applicability of the developed cyclization cascade to substrates that are not suitable for the direct SNAr/5-endo-dig cyclization approach. Successful SEAr in the third position of benzo[b]tellurophene provides a synthetic intermediate for the preparation of Te analogues of selective estrogen receptor modulator (SERM) raloxifene.

Eiropas Sociālā Fonda projekts „Atbalsts doktora studijām Latvijas Universitātē” Nr. 2009/0138/ 1DP/1.1.2.1.2./ 09/IPIA/ VIAA/004

Resveratrol is a natural (poly)phenol primarily found in plants protecting them against pathogens, as well as harmful effects of physical and chemical agents. In higher eukaryotic cells and organisms, this compound displays a remarkable range of biological activities, such as anti-oxidant, anti-inflammatory, anti-cancer, anti-aging, cardio- and neuro-protective properties. Here, biological activities of synthetic selenium-containing derivatives of resveratrol—benzo[b]selenophenes—have been studied in lower eukaryotes Saccharomyces cerevisiae. Their toxicity, as well as DNA damaging and reactive oxygen species (ROS) inducing potencies, manifested through their ability to act as redox active anti-microbial agents, have been examined. We show that some benzo[b]selenophenes can kill yeast cells and that the killing effects are not mediated by DNA damage types that can be detected as DNA double-strand breaks. These benzo[b]selenophenes could potentially be used as anti-fungal agents, although their concentrations relevant to application in humans need to be further evaluated. In addition, most of the studied benzo[b]selenophenes display redox-modulating/anti-oxidant activity (comparable or even higher than that of resveratrol or Trolox) causing a decrease in the intracellular ROS levels in yeast cells. Therefore, after careful re-evaluation in other biological systems these observations might be transferred to humans, where resveratrol-inspired benzo[b]selenophenes could be used as supra-anti-oxidant supplements.

The cyclization of arylalkynes under selenobromination conditions, combined with an acid-induced 3,2-aryl shift, was elaborated as a general synthetic pathway for the preparation of polyhydroxy-2- and -3-arylbenzo[b]selenophenes from the same starting materials. The redox properties, free-radical-scavenging ability, and cytotoxicity against malignant cell lines (MCF-7, MDA-MB-231, HepG2, and 4T1) of the synthesized compounds were explored, and the obtained results were used to consider the structure-activity relationships (SARs) in these compounds. Consequently, the structural features that were responsible for the highly potent peroxyl-radical-scavenging activity were established.

The antioxidant activity of selenium-containing analogs of raloxifene was studied by the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl, superoxide, nitric oxide, and peroxyl radicals. These compounds exhibited similar scavenging properties as resveratrol with respect to superoxide radical and had an impressive activity in peroxyl radical scavenging, making them promising candidates for the development of antioxidant agents.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Microwave-assisted palladium-catalyzed cyanation of 3-bromo-2-(1-hydroxyalkyl)benzo[b]selenophene affords 3-cyano derivatives. Raising the temperature promotes formation of 2-(1-alkenyl)-3-carbamoyl isomers through intramolecular transfer of water.

The cyclization of substituted diaryl(hetaryl)alkynes with in-situ-prepared SeBr4 has been achieved. The use of an alkene additive as a bromine scavenger gives simple access to functionalized benzo[b] selenophene and selenophenothiophene derivatives from commercially available or easily accessible starting materials. The reactions can be performed in air without the use of moisture-sensitive reagents, dry solvents, or an inert atmosphere. Mechanistic studies confirmed a regioselective anti 1,2-addition in the selenobromination step, and a subsequent electrophilic substitution in the aromatic ring to complete the cyclization.

A route for the generation of hypervalent T-shaped 10-Se-3 systems is described involving an interaction between in situ prepared selenium(II) bromide and an aryl alkynyl amide derivative. The existence of hypervalent selenium in both the solid and solution states has been supported by X-ray analysis and 77Se NMR data.

A novel approach for the cyclization of arylalkynes with selenium(IV) bromide prepared in situ has been elaborated. The use of an alkene additive as a bromine scavenger provides a convenient synthetic pathway for the synthesis of a wide variety of 3-bromobenzo[b]selenophenes. Reactions can be performed open to air without the use of moisture-sensitive reagents, anhydrous solvents, or an inert atmosphere. Selenobromination of ethynylthiophenes has been applied for the preparation of selenopheno[3,2-b]- and selenopheno[2,3-b]thiophenes. The molecular structures of representative derivatives have been confirmed by X-ray crystallographic analysis.

AbstractMethods for the synthesis of 3‐cyano‐, 3‐tetrazolyl‐, and 3‐acylamino‐ benzoselenophene derivatives as well as a convenient method for the chlorination of benzoselenophenes at the selenium atom are developed.

Synthetic protocols for the preparation of selenium analogues of raloxifene were elaborated. General aim of the current research is to improve the positive impact of selenium atom introduction in drug design. Antiproliferative activity on CCL-8 (mouse sarcoma), MDA-MB-435s (human melanoma), MES-SA (human uterus sarcoma), MCF-7 (human breast adenocarcinoma), HT-1080 (human fibrosarcoma), MG-22A (mouse hepatoma) tumor cell lines, and normal cell line NIH 3T3 (mouse fibroblasts) was studied. Influence of aminoethoxy “tail” and benzoyl group position on SAR was discussed. Results of in vivo studies on BALB/c female mice with 4T1 cell induced breast cancer model showed that selenium analogue of raloxifene is able to suppress estrogen-depending tumor growth.

Methods have been developed for the preparation of 3-cyano-, 3-tetrazolyl-, and 3-acylamino derivatives of benzoselenophene, as well as a convenient method for the chlorination of benzoselenophene at the selenium atom using sulfuryl chloride to yield 1,1-dichloroselenophenes. The molecular structures of N-(benzoselenophen-3-yl)benzamide and N-(benzoselenophen-3-yl)-3-phenyl-acrylamide have been confirmed by X-ray structural analysis.

AbstractIf a solvent other than dioxane is used for the conversion of (IX) to (X), the respective dialkyne homo coupling product is formed as well besides the desired product (X).

Synthesis, molecular structure and cytotoxic activity of a series of 3-C, N, S, Se substituted benzo[b]selenophene derivatives on human fibrosarcoma HT-1080, mouse hepatoma MG-22A, and mouse fibroblasts 3T3 cell lines are described. The correlation between compound LD(50) 3T3 fibroblast cell line and HT-1080 morphology was shown.

Treatment of nucleobases, nucleosides, 5-membered N-heterocycles and terminal alkynes with trimethoxyvinylsilane in the presence of copper(II) acetate-TBAF system as catalyst affords the vinylation products.