Anti-Picornavirus Activity of Synthetic Flavon-3-yl Esters

Abstract

Members of the family Picornaviridae, which comprise rhinoviruses and enteroviruses, are responsible for several human diseases. It is estimated that over 100 serotypes of human rhinoviruses (HRV) cause approximately half of all cases of the common cold. Also, poliomyelitis still represents a relevant health problem in some countries of the world, despite a dramatic decrease in its incidence as a result of intensive vaccination programmes in developed countries. There therefore exists a need to search for effective chemotherapeutic agents for picornavirus infections.Several classes of flavonoids, isolated from plants utilized in traditional medicine, possess a well recognized anti-picornavirus activity (Van Hoof et al.,1984;Kaul et al., 1985;Tsuchiya et al., 1985). Among polyhydroxylated flavones, quercetin was originally described to reduce the infectivity and the intracellular replication of poliovirus type 1 (PV-1), but not of PV-2 or PV-3. Hesperetin, a flavanone, was able to interfere with PV-1 infection of cell monolayers without affecting virus infectivity (Kaul et al., 1985). 3-Methoxylated flavones, such as chrysosplenol B and C, and axillarin, were found to have potent anti-HRV activity, whereas flavones without a methoxyl group at the 3-position had no anti-rhinovirus activity (Tsuchiya et al., 1985). Beside an effect on HRVs, 4′,5-dihydroxy-3,3′,7-trimethoxyflavone (Ro-09-0179) also exerted an inhibitory activity against coxsackieviruses in tissue cultures (Kaul et al., 1985). The mechanism of action of flavonoids has been attributed to interference with an early stage of viral infection, probably represented by viral RNA synthesis (Castrillo et al., 1986;Gonzales et al., 1990).The study of various synthetic flavones, structurally related to natural flavonoids, confirmed the anti-picornavirus activity of this class of compounds (De Meyer et al., 1991;Desideri et al., 1995). Among the derivatives studied by us, flavanones were generally less effective against picornaviruses than flavones, and 3-hydroxy or 3-methoxyflavones were more active than 3-unsubstituted flavones. The presence of a 3-hydroxy group increased the anti-PV potency, whereas a 3-methoxy group enhanced the effect against HRV-1B ( Desideri et al., 1995). In order to further study the influence on anti-picornavirus activity of the substituent in position 3 of synthetic flavones, we extended our research to esters of chloroflavon-3-ols with natural occurring hydroxybenzoic and hydroxycinnamic acids, i.e. gallic, syringic, caffeic, vanillic and ferulic acids (compounds 2 a-h, 3 a-l). Materials and Methods: VirologyCells HeLa (Ohio) cells were routinely grown at 37°C in 75 cm 2 tissue culture flasks using Eagle's MEM supplemented with 100 µg/ml of streptomycin and 100 U/ml of penicillin G. Eight percent heat-inactivated fetal calf serum (FCS) was added for cell growth (growth medium); the concentration was reduced to 2% for cell maintenance (maintenance medium). The in vitro antiviral activity against picornaviruses (rhinovirus serotype 1B ...

Antiviral activities of some Ethiopian medicinal plants used for the treatment of dermatological disorders

“…Flavonoids as well as sesquiterpenes with anti-herpesvirus and anti-influenzavirus activity have been described (Nagai et al, 1995;Hayashi et al, 1996;Shahat et al, 2002;Chiang et al, 2003;Krawczyk et al, 2003). Although, flavonoids may inhibit picornaviral replication (De Meyer et al, 1991;Conti et al, 1998;Semple et al, 1999), no anti-CVB3 activity of Inula confertiflora extracts was found. Plants containing flavonoids in a sufficiently large concentration were shown to be effective in topical treatment of skin or mucous membrane inflammation (Hoermann and Korting, 1994;Asres et al, 2000).…”

Selective inhibitors of picornavirus replication

“…236 Several synthetic flavonoid and isoflavonoid derivatives were evaluated for their potential antipicornavirus activity. [237][238][239][240][241] In general, flavanones proved to be less active against picornaviruses than flavones, and 3-substitution appeared to be compulsory for potent activity. 242 Among the 3-substituted analogues, the presence of a 3-hydroxy group resulted in increased activity against poliovirus, whereas a 3-methoxy group proved beneficial for the activity against HRV-1B.…”

“…On the other hand, esterification of the 3-hydroxy group with bulky substituents increased toxicity without significantly improving antiviral activity. 237 The synthesis of 2-styrylchromones as vinylogues of flavones, led to the identification of some analogues with antiviral activity against rhinoviruses (with EC 50 values for HRV-14 of 1.33 mM for the best compound in this series). 239 As expected, introduction of a methoxy-or hydroxyl group at position 3 of these 2-styrylchromones led to more potent analogues, with the best compound (''compound 4h'') ( Fig.…”

Effects of sea buckthorn berries on infections and inflammation: a double-blind, randomized, placebo-controlled trial

“…Flavonols along with other flavonoids and polyphenolic compounds influence the immune system and inflammatory cells (Middleton et al, 2000) and have antimicrobial properties (Conti et al, 1998;Middleton et al, 2000;Puupponen-Pimiä et al, 2001). The most convincing evidence on the efficacy of vitamins in CC treatment or prevention concerns people whose immune system may not function optimally or who are under exceptional stress (Hemilä et al, 2002(Hemilä et al, , 2004Meydani et al, 2004).…”