Cysteine-based 3-substituted 1, 5-benzoxathiepin derivatives: Two new classes of anti-proliferative agents

Mahfoudh, N. ; Marin-Ramos, N.I. ; Gil, A.M. ; Jimenez, A.I. (Universidad de Zaragoza) ; Choquesillo-Lazarte, D. ; Kawano, D.F. ; Campos, J.M. ; Cativiela, C. (Universidad de Zaragoza)

Resumen: Two distinct series of the 3-amino-1, 5-benzoxathiepin scaffold, derived from L-cysteine, were synthesized and evaluated for their anti-proliferative activity in the breast cancer MDA-MB-231 and MCF-7 cells, and in the ovarian carcinoma SKOV-3 cell line. (3R)-Amino-3, 4-dihydro-2H-1, 5-benzoxathiepin [(R)-10] was diversified into two forms: (a) by incorporating different amino acids at its position 3, through an amide bond; and (b) by construction of the purine ring to give 6-chloro-9-[2-(3, 4-dihydro-2H-1, 5-benzoxathiepin-(3R)-yl)]-9H-purine [(R)-28]. Nevertheless, when the introduction of iodine was tried at position 2 of the purine ring of (R)-28, 2-{[2-(6-chloro-2-iodo-9H-purin-9-yl) prop-2-en-1-yl] thio} phenol (34) was obtained. Compound 34 shows activity against cancer cells. Interestingly, 34 inhibits mammosphere formation at the micromolar range, demonstrating activity against cancer stem cells. Although further studies of its targets and mechanism of action are needed, these findings support the therapeutic potential of this compound in cancer.

Idioma: Inglés

DOI: 10.1016/j.arabjc.2017.01.011

Año: 2018

Publicado en: ARABIAN JOURNAL OF CHEMISTRY 11, 3 (2018), 426-441
ISSN: 1878-5352

Factor impacto JCR: 3.298 (2018)

Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 59 / 172 = 0.343 (2018) - Q2 - T2

Factor impacto SCIMAGO: 0.605 - Chemistry (miscellaneous) (Q2) - Chemical Engineering (miscellaneous) (Q2)

Financiación: info:eu-repo/grantAgreement/ES/DGA/E40
Financiación: info:eu-repo/grantAgreement/ES/MINECO-FEDER/CTQ2013-40855-R

Tipo y forma: Article (Published version)

Área (Departamento): Área Química Orgánica (Dpto. Química Orgánica)