In silico rationalization of the structural and physicochemical requirements for photobiological activity in angelicine derivatives and their heteroanalogues.
In PUVA (Psoralen plus UVA) chemotherapy 8-methoxypsoralen is the most widely used compound, although its efficacy is endowed with undesired side effects. In order to have an evident anti-proliferative activity with a reduced phototoxicity, many linear and angular derivatives have been synthesised. In this paper we describe a QSAR study in which, by means of the neural networks methodology, a useful model for predicting biological activity, expressed as ID50 (the UVA dose that reduces to 50% the DNA synthesis in Ehrlich cells), has been derived. A decision tree that is able to discriminate between active and inactive compounds has been built based on recursive partitioning. The study shows the key structural features responsible for the activity and could be a helpful tool in the rational design of new, less toxic, photochemotherapeuthic agents.
Giordanetto
Fabrizio
F
Centre for Computational Science, Department of Chemistry, Queen Mary, University of London, Mile End Road, London E1 4NS, United Kingdom.
Fossa
Paola
P
Menozzi
Giulia
G
Mosti
Luisa
L
D000465:Algorithms; D019295:Computational Biology; D011564:Furocoumarins / Q000737:chemistry*; D007364:Intercalating Agents / Q000737:chemistry; D010778:Photochemotherapy; D013329:Structure-Activity Relationship
D011564:Furocoumarins; D007364:Intercalating Agents; C011659:angelicin