title: Study of the biological activity of novel synthetic compounds with antiviral properties against human rhinoviruses.
abstract: Picornaviridae represent a very large family of small RNA viruses, some of which are the cause of important human and animal diseases. Since no specific therapy against any of these viruses currently exists, palliative symptomatic treatments are employed. The early steps of the picornavirus replicative cycle seem to be privileged targets for some antiviral compounds like disoxaril and pirodavir. Pirodavir's main weakness is its cytotoxicity on cell cultures at relatively low doses. In this work some original synthetic compounds were tested, in order to find less toxic compounds with an improved protection index (PI) on infected cells. Using an amino group to substitute the oxygen atom in the central chain, such as that in the control molecule pirodavir, resulted in decreased activity against Rhinoviruses and Polioviruses. The presence of an -ethoxy-propoxy- group in the central chain (as in compound I-6602) resulted in decreased cell toxicity and in improved anti-Rhinovirus activity. This compound actually showed a PI >700 on HRV14, while pirodavir had a PI of 250. These results demonstrate that modification of pirodavir's central hydrocarbon chain can lead to the production of novel derivatives with low cytotoxicity and improved PI against some strains of Rhinoviruses.
authors.affiliation: Sezione di Microbiologia Applicata, Università di Cagliari, via Porcell 4, 09124 Cagliari, Italy. lsamuela@tiscali.it
authors.forename: Samuela
authors.initials: S
authors.lastname: Laconi
authors.forename: Maria A
authors.initials: MA
authors.lastname: Madeddu
authors.forename: Raffaello
authors.initials: R
authors.lastname: Pompei
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D010880:Piperidines / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D011724:Pyridazines / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D012229:Rhinovirus / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D010880:Piperidines; D011724:Pyridazines; C074589:pirodavir