TY - JOUR
T1 - Synthesis and anticancer activity of novel nonfused bicyclic thiazolidinone derivatives
AU - Havrylyuk, Dmytro
AU - Zimenkovsky, Borys
AU - Lesyk, Roman
PY - 2009/3
Y1 - 2009/3
N2 - A series of new 2-{4-oxo-2-[(4-oxothiazolidin-2-ylidene)-hydrazono]- thiazolidin-5-yl}-N-arylacetamides (4a-e), 5-(2-oxo-2-aryl-ethyl)-2-[(4- oxothiazolidin-2-ylidene)-hydrazono]-thiazolidine-4-ones (5a-d), 2-(4-oxo-2-[(2-oxothiazolidin-4-ylidene)-hydrazono]-thiazolidin-5-yl) -N-arylacetamides (7a-e), and 5-(2-oxo-2-aryl-ethyl)-2-[(2-oxothiazolidin-4- ylidene)-hydrazono]-thiazolidine-4-ones (8a-d) have been synthesized starting from 2-thioxothiazolidin-4-one and 4-thioxothiazolidin-2-one through a multistep reaction sequence. 2-Thioxothiazolidin-4-one was alkylated via the intermediate formation of the triethylammonium salt 1 by ethyl chloroacetate. Compound 2 and 4-thioxothiazolidin-2-one reacted with thiosemicarbazides to give the 1-(4-thiazolidinone-2-ylidene)-4-R-thiosemicarbazones (3a,b) and 1-(2-thiazolidinone-4-ylidene)thiosemicarbazones (6a,b), respectively. Following [2+3]-cyclization of thiazolidinone-substituted thiosemicarbazones (3a,b and 6a,b) with N-arylmaleimides and aroylacrylic acids as equivalents of dielectrophilic synthon [C2]2 +, novel non-fused bicyclic thiazolidinones (4a-e, 5a-d, 7a-e, 8a-d) were synthesized. The structures of the new compounds (4a-e, 5a-d, 7a-e, 8a-d) were established on the basis of their elemental analysis and 1H NMR and mass spectral data. Eight of the synthesized compounds were tested, and three of them displayed different levels of antitumor activity. The most efficient antitumor agent2-{4-oxo-3-furylmethyl-2-[(4-oxothiazolidin-2-ylidene)- hydrazono]-thiazolidin-5-yl}-N-4-chlorophenylacetamide (4d) was found to be active against leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancer cell lines with mean lgGI50 and lgTGI values of -5.35 and -4.78, respectively.
AB - A series of new 2-{4-oxo-2-[(4-oxothiazolidin-2-ylidene)-hydrazono]- thiazolidin-5-yl}-N-arylacetamides (4a-e), 5-(2-oxo-2-aryl-ethyl)-2-[(4- oxothiazolidin-2-ylidene)-hydrazono]-thiazolidine-4-ones (5a-d), 2-(4-oxo-2-[(2-oxothiazolidin-4-ylidene)-hydrazono]-thiazolidin-5-yl) -N-arylacetamides (7a-e), and 5-(2-oxo-2-aryl-ethyl)-2-[(2-oxothiazolidin-4- ylidene)-hydrazono]-thiazolidine-4-ones (8a-d) have been synthesized starting from 2-thioxothiazolidin-4-one and 4-thioxothiazolidin-2-one through a multistep reaction sequence. 2-Thioxothiazolidin-4-one was alkylated via the intermediate formation of the triethylammonium salt 1 by ethyl chloroacetate. Compound 2 and 4-thioxothiazolidin-2-one reacted with thiosemicarbazides to give the 1-(4-thiazolidinone-2-ylidene)-4-R-thiosemicarbazones (3a,b) and 1-(2-thiazolidinone-4-ylidene)thiosemicarbazones (6a,b), respectively. Following [2+3]-cyclization of thiazolidinone-substituted thiosemicarbazones (3a,b and 6a,b) with N-arylmaleimides and aroylacrylic acids as equivalents of dielectrophilic synthon [C2]2 +, novel non-fused bicyclic thiazolidinones (4a-e, 5a-d, 7a-e, 8a-d) were synthesized. The structures of the new compounds (4a-e, 5a-d, 7a-e, 8a-d) were established on the basis of their elemental analysis and 1H NMR and mass spectral data. Eight of the synthesized compounds were tested, and three of them displayed different levels of antitumor activity. The most efficient antitumor agent2-{4-oxo-3-furylmethyl-2-[(4-oxothiazolidin-2-ylidene)- hydrazono]-thiazolidin-5-yl}-N-4-chlorophenylacetamide (4d) was found to be active against leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancer cell lines with mean lgGI50 and lgTGI values of -5.35 and -4.78, respectively.
KW - Anticancer activity
KW - Thiazolidinones
KW - [2+3]-cyclization
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U2 - 10.1080/10426500802247563
DO - 10.1080/10426500802247563
M3 - Article
AN - SCOPUS:61449246586
SN - 1042-6507
VL - 184
SP - 638
EP - 650
JO - Phosphorus, Sulfur and Silicon and the Related Elements
JF - Phosphorus, Sulfur and Silicon and the Related Elements
IS - 3
ER -