Synthesis, characterization, crystal structure and cytotoxicity of 2,4-bis(selenomethyl)quinazoline

Abstract

Organoselenium compounds have already been reported to be good anticarcinogenic candidates. A new selenoquinazoline derivative, 2,4-bis(selenomethyl)quinazoline (compound 1), has been synthesized, spectroscopically characterized and its crystal structure has been studied. An intermolecular coupling between C 2 and H 0 5 in the Heteronuclear Multiple Bond Correlation (HMBC) experiment has been observed. Assuming that the headto-tail overlap of parallel molecules (as identified by X-ray diffraction) remains in solution to give bimolecular entities, the p-p interaction enables heteronuclear coupling between the former atoms with a three-bond distance [C 2 ÁÁÁ(p-p)ÁÁÁC 0 5 -H 0 5 ]. The crystal structure of compound 1 has been solved by X-ray diffraction. It crystallizes in triclinic system, space group P-1. Unit cell parameters are a = 7.4969(7) Å , b = 8.7008(8) Å , c = 10.1666(9) Å , a = 110.215(2)°, b = 90.354(2)°, c = 115.017(1)°. Linear chains in crystals of compound 1 are generated by C-HÁÁÁSe and SeÁÁÁSe bonds between molecules. Furthermore, head-to-tail overlap of parallel molecules, in which p-p interactions can occur, is observed. Compound 1 exhibited a cytotoxic effect in all of the evaluated tumoral cell lines and showed a higher cytotoxic effect in colon and breast cancer cell lines than etoposide, which was used as a reference compound.

Novel N,N′-Disubstituted Acylselenoureas as Potential Antioxidant and Cytotoxic Agents

“…During the implementation of our scientific program based in the synthesis and biological evaluation of Se compounds, we have synthetized and observed the antioxidant and anticancer activity of closely related imidoselenocarbamates [26][27][28][29][30][31][32][33][34], seleno-quinazoline, and pyrido [2,3-d]pyrimidine derivatives [33,[35][36][37]. Some evidence has pointed out that relatively simple selenoureas ( Figure 1A) might possess a superoxide radical scavenging activity accompanied by a low toxicity in human cells [38].…”

Novel Library of Selenocompounds as Kinase Modulators

“…Compounds of C series were synthesized from the appropriate ortho -aromatic diamine and selenium dioxide [ 36 ] and transformed into amides by reaction of the carboxylic acid with thionyl chloride and the appropriate amine or diamine. Compounds of D series were prepared by reaction of the corresponding quinazoline or pyrido[2,3- d ]pyrimidine with phosphoryl chloride and the intermediate dihalogenated derivative was treated with selenourea in absolute ethanol [ 37 ]. Finally, the diselenide compound E was synthesized by addition of selenium dioxide to malononitrile in DMSO followed by reaction with ortho -amino benzoic acid.…”

“…Compounds were prepared using the synthetic routes previously reported [ 34 , 35 , 36 , 37 , 38 , 39 ]. All library compounds were evaluated to verify identity by IR, 1 H-NMR and to verify purity by elemental microanalyses.…”

“…Taking into account the urgent need of new chemical approaches for the discovery of novel compounds that are capable of inhibiting kinase activation, we describe in this paper the screening of a kinase-directed library, which comprises a broad structural variety and includes: Se -alkyl imidoselenocarbamates ( A ), selenylacetic acids ( B ), selenodiazoles ( C ), selenolderivatives ( D ) and a diselenide compound ( E ). This approach is based on the promising cytotoxic activity of compounds previously reported by our group [ 34 , 35 , 36 , 37 , 38 ] and will be considered, as a starting point for a new strategy, in the design and development of new anticancer candidates.…”