Structure–activity relationship study of arbidol derivatives as inhibitors of chikungunya virus replication

The medicinal chemistry of Chikungunya virus

“…31 Di Mola et al 71 have used (2) to design novel analogs with anti-CHIKV activity, aiming to improve the (2) therapeutic index or to identify novel lead compounds. It was observed that (2) inhibits CHIKV infection with IC 50 value at 12.2 lM.…”

“…The substitution of the ethyl ester at position 2 with a tert-butyl ester resulted in compounds more actives, with EC 50 values ranging from 11 to 27.8 lM. 71 The oxidation of compounds (14), (15) and (16) to sulfoxides (23), (24) and (25) led a decrease in anti-CHIKV activity and cytotoxicity. Finally, it obviously noted which the presence of an electron-withdrawing group at the para position of the thiophenol ring (14-16, and 19) lead to molecules with an antiviral activity more than that (2).…”

“…Based on results obtained by Di Mola et al, 71 new arbidol analogs were proposed by Scuotto et al 55 In this study, three new series of compounds were synthesized and evaluated against CHIKV in Vero cells using CPE assay ( Table 2). In addition, the E 2 unit of the crystal structure of the mature E 3 -E 2 -E 1 glycoprotein complex (PDB ID: 3N42) was used in the simulations (Gly407 corresponds to Gly82 in the crystal structure), two potential binding sites in the proximity of Gly82 were identified.…”

Towards antivirals against chikungunya virus

“…Arbidol was reported to inhibit CHIKV infection in MRC-5 cells with an EC 50 of 12 lM (Delogu et al, 2011). Two analogues of arbidol were recently identified that had a somewhat higher selectivity index for inhibition of in vitro replication of CHIKV (Di Mola et al, 2014). An arbidol-resistant mutant strain was identified with a mutation of a glycine to an arginine (G407R) in the CHIKV E2 glycoprotein (Delogu et al, 2011).…”

Combinatorial Chemistry Online Volume 17, Issue 1, January 2015

“…One of these is Arbidol, a molecule that has been licensed for the treatment of influenza A and B virus infections. For structural optimization, a dedicated library of 43 indole-based derivatives was evaluated leading to more potent analogues with anti-CHIKV activities [13].…”