Synthesis and anti-tumor activity of 2-[(5-arylfuran-2-ylmethylene)-hydrazone]-thiazolidine-4-one

Abstract

The thiazolidin-4-ones are an important class of attractive compounds. They exhibit a wide range of pharmacological activity. 4-Thiazolidone motif is considered as privileged scaffolds in medicinal chemistry and are is currently the subject of extensive research. No less interesting is the search for novels biologically activity compounds among the derivatives of furane. It is widely found in diverse pharmacologically active substances and naturally-occurring compounds. Among furane derivatives arylfuranes play also imported role in drug design and discovery. The objective of the present work was to synthesize a series of novel 2-[(5-arylfuran-2-ylmethylene)-hydrazone]-thiazolidine-4-ones. The corresponding thiosemicarbazones were synthesized by the interaction of 5-arylfuran-2-carbaldehydes with thiosemicarbazide. It was shown that they cyclocondensate with chloroacetic acid and ethyl 3-aryl-2-bromopropanate to form 2-[(5-aryl-2-ylmethylene) -hydrazono]-thiazolidin-4-ones. The structures of the obtained compounds were confirmed by 1H spectroscopy and elemental analysis. All these new compounds gave spectroscopic data in accordance with the proposed structures. Synthesized derivatives 6 a-b and 7 a-h were selected by National Cancer Institute (NCI, Bethesda USA) Developmental Therapeutic Program (DTP) and evaluated for anticancer activity at the concentration of 10 -5 M toward a panel of approximately sixty cancer cell lines (http://dtp.nci.nih.gov). The human tumor cell lines were derived from nine different cancer types: leukemia (CCRF-CEM, HL-60(TB), K-562, MOLT-4, RPMI-8226), melanoma (LOXIMVI, MALME-3M, M14, SK-MEL-2, SK-MEL-28, SK-MEL-5, UACC-257, UACC-62), lung (A549/ATCC, EKVX, HOP-62, HOP-92, NCI-H226, NCI-H23, NCI-H322M, NCI-H460, NCIH522), colon (COLO 205, HCT-116, HCT-15, HT29, KM12, SW-620), central nervous system (SF268, SF-295, SF-539, SNB-19, SNB-75, U251), ovarian (IGROV-1, OVCAR-3, OVCAR-4, OVCAR-5, SK-OV-3), renal (786-0, A498, ACHN, CAKI-1, RXF-393, SN12C, TK-10, UO-31), prostate (PC-3, Du-145) and breast cancers (MCF7, NCI/ADR-RES, MDA-MB-231/ATCC, HS 578T, MDA-MB-435, BT-549, T-47D). The results for each tested compound were reported as the growth percentage of the treated cells when compared to that of the untreated control cells. The test compounds show moderate antitumor activity. The UO-31 renal cancer line was sensitive to 2 -{[5- (4-Chlorophenyl) -furan-2-ylmethylene] -hydrazono} -5- (4-methoxybenzyl) -thiazolidin-4-one. Moderate HOP-92 activity in non-small cell lung cancer was also observed for most compounds. Keywords : organic synthesis, cyclocondensation, thiosemicarbazide, thiazolidin-4-one, furan.