In vitro study reveals potent inhibition of cytomegalovirus and rhinovirus by novel oxazole derivatives, indicating their potential as targeted antiviral therapeutics.
Key Points
To synthesize a library of functionalized 1,3-oxazole and 1,2,4-oxadiazole derivatives and evaluate their antiviral efficacy and pharmacological properties against multiple virus models.
Synthesized 16 functionalized 2-undecyl- and 1,2,4-oxadiazole-containing 2-aryl-4-cyano-1,3-oxazoles using α-acylamino-β,β-dichloroacrylonitriles as building blocks.
Screened antiviral activity in vitro against human rhinovirus 8 (HRV8), human cytomegalovirus (HCMV), parainfluenza virus type 3 (HPIV-3), and encephalomyocarditis virus (EMCV), followed by ADMET predictions and molecular docking.
Compounds 1, 7, 10, 13, and 14 showed potent anti-HCMV activity with IC50 values from 0.42 to 4.67 µM, with compound 7 demonstrating higher selectivity (SI = 465) than ganciclovir (SI = 326).
Compound 2 proved most effective against HRV8 (IC50 = 1.67 µM, SI = 11), while none of the synthesized compounds exhibited inhibitory activity against HPIV-3 or EMCV.
Molecular docking demonstrated strong binding affinities of derivatives 7, 10, 13, and 14 toward viral DNA polymerase, with binding energies ranging from –8.8 to –9.7 kcal/mol.