Synthesis and antirhinovirus activity of new 3-benzyl chromene and chroman derivatives.
A series of 3-benzyl chromenes and chromans were synthesized and tested in vitro against human rhinovirus (HRV) 1B and 14, two representative serotypes for rhinovirus group B and A, respectively. All the new compounds, with the exception of 3-benzyl-2H-chromene (3a), showed a potent activity against HRV serotype 1B within micro or submicromolar range (IC(50)s from 0.11 to 6.62 microM). The low cytotoxicity of all the derivatives resulted in compounds with high therapeutic index (TI). On the contrary, HRV 14 infection was only weakly inhibited by the majority of these compounds. The 3-benzylidenechromans 2b and 2c showed the highest anti-HRV 1B activity (IC(50) 0.12 and 0.11 microM, respectively) coupled with remarkable TI (625.00 and 340.91, respectively). Mechanism of action studies on (Z)-3-(4-chlorobenzylidene)chroman (2b) suggest that the new compounds behave as capsid binders and interfere with very early stages of HRV 1B replication, similarly to related flavanoids.
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Istituto Pasteur Fondazione Cenci Bolognetti, Dipartimento di Scienze di Sanità Pubblica, Sezione di Microbiologia, Università 'La Sapienza' di Roma, P.le A. Moro, 5, 00185 Roma, Italy.
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D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D002839:Chromans / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D012229:Rhinovirus / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
C541661:(Z)-3-(4-chlorobenzylidene)chroman; C541662:(Z)-6-chloro-3-(4-chlorobenzylidene)chroman; C541660:3-benzyl-2H-chromene; D000998:Antiviral Agents; D001578:Benzopyrans; D002839:Chromans