Synthesis, in silico and in vitro studies of piperazinyl thiourea derivatives as apoptosis inducer for the treatment of colorectal carcinoma

A series of piperazine bearing thiourea compounds with different substitutions (L1-L13) was synthesized for the treatment of colorectal carcinoma. The spectroscopic characterizations like UV-Vis, FT-IR, and H-1/C-13/DEPT 135 NMR were employed for the compound confirmation. Crystallographic study of L1, L2, and L5 revealed that the compounds crystallized in a triclinic fashion. Calf thymus (CT) DNA absorption study, ethidium bromide (EB) displacement study, and viscosity study revealed that all compounds bound to DNA via intercalation displaying a good binding (K-b) constant. Further, in vitro cytotoxicity results showed that 4-methyl-N-((4-(4-phenylpiperazin-1-yl)phenyl)carbamothioyl)benzamide (L2) exhibited the best cytotoxicity on the cisplatin-resistant HCT116+ch3 cells, but was less effective in HCT116 and SW620 cells. Moreover, L2 also exhibited high cell selectivity towards cancer cells over normal human FHC cells, indicating the potential of L2 in cancer-therapy. Furthermore, L2 induced apoptosis in HCT116+ch3 cells via involving the cleavage of caspase-8 and PARP. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

A series of piperazine bearing thiourea compounds were synthesized for the treatment of colorectal carcinoma. Compound L2 exhibited good cytotoxicity, especially against cisplatin-resistant cells, showing potential for cancer therapy.