Synthesis of a New Class of ß-Carbonyl Selenides Functionalized with Ester Groups with Antioxidant and Anticancer Properties-Part II.

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.

Exploring Novel Drug Combinations: The Therapeutic Potential of Selanyl Derivatives for Leishmania Treatment.

This work describes the design, synthesis, and biological activities of new selenoester derivatives and its homologs thioesters. Thirty-two compounds were developed following an economical synthetic route, achieving small molecules, with structural characteristics similar to those present in antileishmanial drugs such as miltefosine (MIL) and paromomycin (PMN). These compounds were tested in vitro against strains of Leishmania major (L. major) and Leishmania infantum (L. infantum). The L. infantum strain (causative agent of visceral leishmaniasis) exhibited the highest sensitivity. Thus, four selanylacetic acid derivatives (A4, A5, A6 and A8) presented IC50 values below 40 µM in this strain. These derivatives also demonstrated low toxicity and high selectivity in PMA-differentiated THP-1 macrophages. The A4-A6 and A8 derivatives were evaluated in order to determine their pharmacological behavior, using drug combination studies with the reference drugs amphotericin B (AMB), MIL and PMN. Compounds A6 and A8 presented a potent synergistic interaction with MIL, which is the only oral drug available for the treatment of visceral leishmaniasis. Therefore, compounds A6 and A8 present significant potential as therapeutic candidates for the treatment of leishmaniasis based on their remarkable leishmanicidal characteristics and pharmacological synergism.

Synthetic Approaches to Selenoesters.

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.

Synthesis of New Chiral ß-Carbonyl Selenides with Antioxidant and Anticancer Activity Evaluation-Part I.

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.

[4-(4-Meth-oxy-phen-yl)-8-oxo-3-(phenyl-selan-yl)spiro-[4.5]deca-3,6,9-trien-2-yl]methyl-cyanamide.

The title compound, C25H22N2O2Se, crystallizes in the space group P21/c with one mol-ecule in the asymmetric unit. The compound was synthesized by the addition of phenyl-selenyl bromide to a cyanamide. The phenyl-selenyl portion and the cyano group, as well as the ketone functional group in the cyclo-hexa-2,5-dien-1-one portion of the structure, are disordered, with occupancy factors of 0.555 (14) and 0.445 (14).