title: 3-Phenylalkyl-2H-chromenes and -chromans as novel rhinovirus infection inhibitors.
abstract: Following our studies on structure-activity relationships of anti-rhinovirus chromene and chroman derivatives, we designed and synthesized new series of 3-phenylalkyl-2H-chromenes and -chromans bearing differently sized, aliphatic linker chains between the two cycles. The cytotoxicity and the antiviral activity of the new compounds on human rhinovirus (HRV) serotype 1B and 14 infection were evaluated in HeLa cell cultures. Most of the tested compounds interfered with HRV1B multiplication in the micromolar or submicromolar concentrations while HRV14 was less susceptible. 3-[3-(4-Chlorophenyl)propyl]chroman (9c) was selected for preliminary mechanism of action studies due to its potent activity against both serotypes (IC50of 0.48μM and 1.36μM towards HRV1B and 14, respectively) coupled with high selectivity (SI=206.18 and 73.26, respectively). Results of time of addition/removal studies suggest that 9c, similarly to related derivatives, behaves as a capsid binder interfering with some early events of the HRV1B infectious cycle.
authors.affiliation: Dipartimento di Scienze di Sanità Pubblica, Sezione di Microbiologia, Università "La Sapienza" di Roma, P.le A. Moro, 5, 00185 Roma, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Conti
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Università "La Sapienza", P.le A. Moro, 00185 Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Proietti Monaco
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Università "La Sapienza", P.le A. Moro, 00185 Rome, Italy. Electronic address: nicoletta.desideri@uniroma1.it.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Desideri
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D066244:Proton Magnetic Resonance Spectroscopy; D012229:Rhinovirus / Q000187:drug effects*; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D001578:Benzopyrans
keywords: 2H-Chromenes; Antiviral activity; Capsid binders; Chromans; Rhinovirus