New aryl-/heteroarylpiperazine derivatives of 1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.0 < sup > 2,6 < /sup > ]dec-8-ene-3,5,10-trione: Synthesis and preliminary studies of biological activities

Bioorg Med Chem. 2023 Nov 7;96:117518. doi: 10.1016/j.bmc.2023.117518. Online ahead of print.ABSTRACTCompounds containing dicarboximide skeleton such as succinimides, maleimides, glutarimides, and phthalimides possess broad biological properties including anti-fungal, antibacterial, antidepressant, or analgesic activities. The piperazine ring is found in a wide range of molecules that have demonstrated a variety of biological functions such as anticancer action and 5-HT receptors agonist/antagonist activity. In the present study, we combined both structures to develop new antitumor agents, a series of piperazine derivatives of 1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5,10-trione and evaluated their biological activity. The structures of all tested compounds were confirmed by 1H and 13C NMR and by ESI MS spectral analysis. Their cytotoxicity was assessed in vitro against eight human cancer cell lines, namely prostate (PC3), colon (HCT116, SW480, SW620), leukemia (K562), liver (HepG2), lung (A549) and breast (MDA-Mb-231) in contrast to normal HMEC-1 cell line, by using MTT and Trypan blue method. The tested compounds showed significant activity toward cancer cells. The most pronounced cytotoxic effect was observed in K562 and HCT116 with IC50 values below 10 μM for all studied compounds. Importantly, the most promising derivatives for each cancer cell line (IC50 < 10 μM) exerted a weaker cytotoxic effect toward normal HMEC-1 cells than cancer cells. T...
Source: Bioorganic and Medicinal Chemistry - Category: Chemistry Authors: Source Type: research