• 1 Department of Chemistry, Shahjalal University of Science and Technology, Sylhet, Bangladesh
  • 2 EMAN Research and Testing Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia
  • 3 The School of Chemical Sciences, Universiti Sains Malaysia (USM), Penang, Malaysia
  • 4 Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
  • 5 EMAN Biodiscoveries Sdn. Bhd., EUREKA Complex, Universiti Sains Malaysia (USM), Penang, Malaysia
Drug Dev Res, 2019 09;80(6):778-790.
PMID: 31215682 DOI: 10.1002/ddr.21559


The bidentate N-cyclohexyl-2-(3-hydroxy-4-methoxybenzylidene)hydrazine-1-carbothioamide Schiff base ligand (HL) was coordinated to divalent nickel, palladium and platinum ions to form square planar complexes. The nickel and palladium complexes, [NiL2 ], [PdL2 ] form square planar complexes with 2:1 ligand to metal ratio. The platinum complex, [PtL(dmso)Cl] formed a square planar complex with 1:1 ligand to metal ratio. Platinum undergoes in situ reaction with DMSO before complexing with the ligand in solution. The cytotoxicity of HL, [NiL2 ], [PdL2 ], and [PtL(dmso)Cl] were evaluated against human colon cancer cell line (HCT-116), human cervical cancer (Hela) cell line, melanoma (B16F10) cells, and human normal endothelial cell lines (Eahy926) by MTT assay. The [NiL2 ] complex displayed selective cytotoxic effect against the HCT 116 cancer cell line with IC50 of 7.9 ± 0.2 μM. However, HL, [PdL2 ], and [PtL(dmso)Cl] only exhibited moderate cytotoxic activity with IC50 = 75.9 ± 2.4, 100.0 ± 1.8, and 101.0 ± 3.6 μM, respectively. The potent cytotoxicity of [NiL2 ] was characterized using Hoechst and Rhodamine assays. The nickel complex, [NiL2 ], caused remarkable nuclear condensation and reduction in mitochondrial membrane potential. In addition, molecular docking studies confirms that [NiL2 ] possesses significant binding efficiency with Tyrosine kinase. Altogether, the results revealed that [NiL2 ] exhibits cytotoxicity against the cancer cells via Tyrosine kinase-induced proapoptosis pathway. This study demonstrates that the [NiL2 ] complex could be a promising therapeutic agent against colorectal carcinoma.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.