An Efficient Synthesis and Antiviral Activity Evaluation of 1-[4-(5-Phenyl- 4, 5 dihydro-1H-pyrazole [& (4, 5 dihydroisoxazole)]-3-yl)-phenyl]-pyrrole- 2, 5-dione Derivates

Preparation of new series of 1-[4-(5-Phenyl-4,5 dihydro-1H-pyrazole-3-yl)-phenyl]-pyrrole-2,5-dione and 1-[4- (5-Phenyl-4,5 dihydroisooxazole-3-yl)-phenyl]-pyrrole-2,5-dione derivatives, derived from α,β-unsaturated ketones with objective of obtaining lead compounds for future development as antiviral agents. The inhibition of virus-induced cytopathicity or plaque formation in HEL [herpes simplex virus type 1 (HSV-1) (KOS), HSV-2 (G), vaccinia virus, vesicular stomatitis virus, cytomegalovirus (HCMV), and varicella-zoster virus (VZV)], Vero (parainfluenza-3, reovirus-1, Sindbis virus and Coxsackie B4), HeLa (vesicular stomatitis virus, Coxsackie virus B4, and respiratory syncytial virus) or MDCK [influenza A (H1N1; H3N2) and influenza B] cell cultures by synthesized derivatives. All the compounds were characterized by physical, spectroscopic and elemental analysis. Among the fourteen synthesized targets only compounds 3g and 4e showed activity against RSV (EC50 = 37 µ M and 46 µ M with affecting cell morphology at concentrations of, respectively, 254 µ M and 286 µ M) Compound 3g also showed weak activity against feline corona virus (EC50 value of 29 µM and a MCC of 107 µ M) for CRFK cells. Feline corona virus was also weakly inhibited by compound 3f (EC50=39 µM) that altered cell morphology at a concentration of 231 µ M. Except for feline corona virus, none of the other viruses was inhibited by compound 3f. Low selectivity indices (SIs), defined as ratio MCC/EC50, were observed SI=4 and SI=6 for compounds 3g and 3f against feline corona virus respectively, while SI=6 for compound 4e against RSV, and SI=7 for compound 3g against RSV. Biological evaluation was performed using acyclovir, brivudin, gancilcovir, cidofovir against herpes and poxviruses while ribavirin against RNA viruses, reference standard drugs.