New derivatives of xanthenone-4-acetic acid: synthesis, pharmacological profile and effect on TNF-alpha and NO production by human immune cells.
New derivatives of xanthenone-4-acetic acid, bearing an alkoxy chain of variable length and a basic moiety, were synthesised in order to test the influence of this additional function on antitumour activity. The introduction of bulky substituents carrying a basic nitrogen seems to be somewhat tolerated, since for some of the compounds the enhancement of lytic potential of human monocytes was comparable to that of the reference molecule DMXAA. The induction of the release of TNF-alpha and nitric oxide by human monocytes, as well as the hypothesis of a potentiation of the activity of lipopolysaccharide in the induction of those cytotoxic factors, was also evaluated. In this respect, the most interesting compound (6a) exhibited the same spectrum of biological activity shown by DMXAA and seems therefore to be endowed with the same mechanism of action of the reference compound.
Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. silvia.gobbi@unibo.it
Silvia
S
Gobbi
Federica
F
Belluti
Alessandra
A
Bisi
Lorna
L
Piazzi
Angela
A
Rampa
Antonella
A
Zampiron
Mariagnese
M
Barbera
Anna
A
Caputo
Maria
M
Carrara
D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D009569:Nitric Oxide / Q000096:biosynthesis*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000187:drug effects; D014966:Xanthenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D044004:Xanthones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D014966:Xanthenes; D044004:Xanthones; C066668:vadimezan; D009569:Nitric Oxide; C066138:xanthenone-4-acetic acid