Study on Quinazolinone and Thiazolidinone
General Papers
ARKIVOC 2006 (i) 109-118
Synthesis and primary antiviral activity evaluation of 3-hydrazono-5-nitro-2-indolinone derivatives
Nalan Terzioğlu *a, Nilgün Karalı a, Aysel Gürsoy a, Christophe Pannecouque b, Pieter Leysen b, Jan Paeshuyse b, Johan Neyts b, and Erik De Clercq b a Istanbul University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 34116, Istanbul, Turkey b Rega Institue of Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium E-mail: nalant@yahoo.com
Abstract A series of 5-nitro-3-[(5-nonsubstituted/methyl-4-thiazolidinone-2-ylidene)hydrazono]-1H-2indolinones (3a-j and 4a-h) was synthesized by cyclization of 5-nitro-1H-indole-2,3-dione-3thiosemicarbazones (1a-k) with ethyl bromoacetate or ethyl 2-bromopropionate. The primary antiviral activities of the new hydrazonoindolinone derivatives, the previously reported 5-nitro1H-indole-2,3-dione-3-thiosemicarbazones (1a-k) and 1-morpholino/piperidinomethyl-5-nitroindole-2,3-dione-3-thiosemicarbazones (2a-l) were evaluated against some pathogenic viruses in the Rega Institue for Medical Research, Belgium. Among the tested compounds, 1c, 2b and 3b afforded some weak activity against the yellow fever virus (YFV) in vero cells, whereas compounds 2b, 3a, 3f, 4e and 4f inhibited the growth of bovine viral diarrhea virus (BVDV) in MDBK CODA cells. Keywords: 1H-2-Indolinones, 4-thiazolidinones, antiviral activity
Introduction
Isatin (1H-indole-2,3-dione) is a versatile lead molecule for designing potential antiviral agents. Several authors found that isatin-β-thiosemicarbazone (1H-indole-2,3-dione-3thiosemicarbazone) and its N-Mannich bases were active against various viruses1. The first clinically approved antiviral agent, N-methylisatin-β-thiosemicarbazone (methisazone, I), and isatin-β-thiosemicarbazone (II) are active against poxviruses2. Antiviral properties of certain thiourea and semicarbazone derivatives have been reported in which the antiviral
ARKIVOC 2006 (i) 109-118
Synthesis and primary antiviral activity evaluation of 3-hydrazono-5-nitro-2-indolinone derivatives
Nalan Terzioğlu *a, Nilgün Karalı a, Aysel Gürsoy a, Christophe Pannecouque b, Pieter Leysen b, Jan Paeshuyse b, Johan Neyts b, and Erik De Clercq b a Istanbul University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 34116, Istanbul, Turkey b Rega Institue of Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium E-mail: nalant@yahoo.com
Abstract A series of 5-nitro-3-[(5-nonsubstituted/methyl-4-thiazolidinone-2-ylidene)hydrazono]-1H-2indolinones (3a-j and 4a-h) was synthesized by cyclization of 5-nitro-1H-indole-2,3-dione-3thiosemicarbazones (1a-k) with ethyl bromoacetate or ethyl 2-bromopropionate. The primary antiviral activities of the new hydrazonoindolinone derivatives, the previously reported 5-nitro1H-indole-2,3-dione-3-thiosemicarbazones (1a-k) and 1-morpholino/piperidinomethyl-5-nitroindole-2,3-dione-3-thiosemicarbazones (2a-l) were evaluated against some pathogenic viruses in the Rega Institue for Medical Research, Belgium. Among the tested compounds, 1c, 2b and 3b afforded some weak activity against the yellow fever virus (YFV) in vero cells, whereas compounds 2b, 3a, 3f, 4e and 4f inhibited the growth of bovine viral diarrhea virus (BVDV) in MDBK CODA cells. Keywords: 1H-2-Indolinones, 4-thiazolidinones, antiviral activity
Introduction
Isatin (1H-indole-2,3-dione) is a versatile lead molecule for designing potential antiviral agents. Several authors found that isatin-β-thiosemicarbazone (1H-indole-2,3-dione-3thiosemicarbazone) and its N-Mannich bases were active against various viruses1. The first clinically approved antiviral agent, N-methylisatin-β-thiosemicarbazone (methisazone, I), and isatin-β-thiosemicarbazone (II) are active against poxviruses2. Antiviral properties of certain thiourea and semicarbazone derivatives have been reported in which the antiviral
References: 464. (c) Balzarini, J.; Naesens, L.; Slachmuylders, J.; Niphuis, H.; Rosenberg, I.; Holy, A.; Schellekens, H.; De Clercq, E. AIDS 1991, 5, 21. (d) Neyts, J.; Meerbach, A.; McKenna, P.; De Clercq, E. Antiviral Res. 1996, 30, 125.