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 (IC50 of 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.

3-Phenylalkyl-2H-chromenes and -chromans as novel rhinovirus infection inhibitors / Conti, Cinzia; PROIETTI MONACO, Luca; Desideri, Nicoletta. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - STAMPA. - 25:7(2017), pp. 2074-2083. [10.1016/j.bmc.2017.02.012]

3-Phenylalkyl-2H-chromenes and -chromans as novel rhinovirus infection inhibitors

CONTI, Cinzia;PROIETTI MONACO, LUCA;DESIDERI, Nicoletta
2017

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 (IC50 of 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.
2017
2H-chromenes; antiviral activity; capsid binders; chromans; rhinovirus; biochemistry; molecular medicine; molecular biology; 3003; drug discovery3003 pharmaceutical science; clinical biochemistry; organic chemistry
01 Pubblicazione su rivista::01a Articolo in rivista
3-Phenylalkyl-2H-chromenes and -chromans as novel rhinovirus infection inhibitors / Conti, Cinzia; PROIETTI MONACO, Luca; Desideri, Nicoletta. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - STAMPA. - 25:7(2017), pp. 2074-2083. [10.1016/j.bmc.2017.02.012]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/961261
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