Synthesis and anticancer activity of (R,S)-9-(2,3-dihydro-1,4-benzoxathiin-3-ylmethyl)-9H-purines.
A series of eleven 2- and 6-substituted (R,S)-9-(2,3-dihydro-1,4-benzoxathiin-3-ylmethyl)-9H-purine derivatives was obtained by applying a standard Mitsunobu protocol that led to a six-membered ring contraction from (R,S)-3,4-dihydro-2H-1,5-benzoxathiepin-3-ol via an episulfonium intermediate. The signal approximately delta=151 ppm, which corresponds to the C4' carbon atom, is unequivocal proof of the N9' regioisomer. The potential of the target molecules as anticancer agents is reflected in their activity against the MCF-7 cancer cell line. The most active compounds have IC(50) values of (6.18+/-1.70) and (8.97+/-0.83) microM. The results indicate that the anticancer activity for the most active compounds is correlated with their capacity to induce apoptosis.
Díaz-Gavilán
Mónica
M
Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, c/Campus de Cartuja s/n, 18071 Granada, Spain.
Conejo-García
Ana
A
Cruz-López
Olga
O
Núñez
María C
MC
Choquesillo-Lazarte
Duane
D
González-Pérez
Josefa M
JM
Rodríguez-Serrano
Fernando
F
Marchal
Juan A
JA
Aránega
Antonia
A
Gallo
Miguel A
MA
Espinosa
Antonio
A
Campos
Joaquín M
JM
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018360:Crystallography, X-Ray; D005260:Female; D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D009584:Nitrogen / Q000737:chemistry; D010075:Oxathiins / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D011687:Purines / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D010075:Oxathiins; D011687:Purines; D009584:Nitrogen