title: Naphthylnitrobutadienes as pharmacologically active molecules: evaluation of the in vivo antitumour activity.
abstract: On the basis of our previous interesting results in vitro on the antiproliferative activity of (1E,3E)-1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene (1-Naph-DNB) we have designed and synthesized the new molecule methyl (2Z,4E)-2-methylsulphanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate (1-Naph-NMCB) characterized by the same naphthylnitrobutadiene array but with a different functional group at one end of the diene system. This new molecule showed an in vitro antiproliferative activity more significant than that found for the original 1-Naph-DNB. In order to verify in vivo our in vitro results we have tested the antitumour activity of 1-Naph-DNB and 1-Naph-NMCB in several murine tumour models, namely the myelomonocytic P388 and the Lewis lung carcinoma 3LL in BDF1 mice, the melanoma B16 in C57Bl mice, the fibrosarcoma WEHI 164 in nude mice and, finally, the C51 colon cancer in Balb/c mice. In the case of 1-Naph-NMCB the analysis of the antitumour activity has been preceded by toxicological experiments on CD-1 mice, in order to determine the lethal (LD) and the maximal tolerated (MTD) doses together with the spectrum of histological alterations caused by its iv administration. The results obtained show that the modification of the original structure of 1-Naph-DNB according to the molecular-simplification strategy has led to an asymmetric nitrobutadiene array, i.e. that of 1-Naph-NMCB, endowed with an antitumour activity which is in some cases even better than that showed by the parental compound itself, together with differences in tumour selectivity and negligible histological toxic effects.A promising, versatile route to new, more active and/or safe nitrobutadiene derivatives has thus been positively tested.
authors.affiliation: Dipartimento di Chimica e Chimica Industriale, Università di Genova, Via Dodecaneso 31, 16146, Genoa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Petrillo
authors.forename: Carla
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Emanuela
authors.initials: E
authors.lastname: Ognio
authors.forename: Cinzia
authors.initials: C
authors.lastname: Aiello
authors.forename: Domenico
authors.initials: D
authors.lastname: Spinelli
authors.forename: Maria A
authors.initials: MA
authors.lastname: Mariggiò
authors.forename: Massimo
authors.initials: M
authors.lastname: Maccagno
authors.forename: Stefano
authors.initials: S
authors.lastname: Morganti
authors.forename: Cinzia
authors.initials: C
authors.lastname: Cordazzo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Viale
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D002070:Butadienes / Q000494:pharmacology* / Q000633:toxicity; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009281:Naphthalenes / Q000494:pharmacology*; D018675:Toxicity Tests; D023041:Xenograft Model Antitumor Assays
chemical_list: C500384:1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene; D000970:Antineoplastic Agents; D002070:Butadienes; D005231:Fatty Acids, Unsaturated; D009281:Naphthalenes; C526679:methyl 2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate