Abstract
In a bid to come up with potential anticancer agents, a class of thiosemicarbazone ligands bearing substituted thiophene were synthesized followed by complexation with various Pd(II) and Pt(II) metal precursors. The ligands (E)-1-((thiophen-2-yl)methylene)thiosemicarbazide (L1), (E)-1-((4-bromothiophen-2-yl)methylene)thiosemicarbazide (L2), and (E)-1-((5-bromothiophen-2-yl)methylene)thiosemicarbazide (L3) were synthesized by condensation reactions and obtained in good yields. Complexation of L1 and L2 with Pd(cod)Cl2 gave C1 (C6H7Cl2N3PdS2) and C2 (C6H6BrCl2N3PdS2), respectively. Complexation of L1 with K2PtCl4 gave C3 (C6H7Cl2N3PtS2), while L3 with K2PtCl2[(PPh)3]2 gave C4 (C24H21BrClN3PPtS2). The structures and coordination for all compounds were established by FTIR, 1H-NMR, 13C-NMR, UV-Vis, elemental analysis, and single-crystal X-ray diffraction studies for ligand L1. Tuning of the spectral and anticancer activity of the compounds was investigated by changing the position of the bromide substituent, metal center, and the σ or π-donor/acceptor strength of the groups surrounding the metal center. The compounds had low to moderate anticancer potency with their spectral and structural properties correlating with the corresponding anticancer activity profiles. DNA binding modes were studied by spectroscopy and were comparable to known DNA intercalators. Structure-activity profiles were evident especially between C1 and C2 differing by the presence of a Br in position 5 of thiophene ring, which caused a remarkable increase in IC50 values, from 14.71 ± 0.016 (C1) to 43.08 ± 0.001(C2) in Caco-2 cells, 1.973 ± 0.048 (C1) to 59.56 ± 0.010 (C2) in MCF-7 cells, 16.65 ± 0.051 (C1) to 72.25 ± 0.003 (C2) in HeLa cells, 14.64 ± 0.037 (C1) to 94.34 ± 0.003 (C2) in HepG2, and 14.05 ± 0.042 (C1) to >100(C2) in PC-3 cells.
Highlights
Cancer is the second leading cause of death globally, with an estimated 1 in 6 deaths, and is responsible for an estimated 9.6 million deaths in 2018 [1]
Is work reports the anticancer activity of newly synthesized Pd(II) and Pt(II) complexes bearing thiosemicarbazone ligands. e main objectives were to evaluate the tuning of structure-activity relationships vis-a-vis different σ and/or π-donor/acceptor properties of the groups attached to the metal center, their anticancer activities, and their binding modes to DNA
Bioassays on the anticancer efficacy were performed at the Department of Biotechnology at the University of the Western Cape. e elemental microanalysis was performed on Server 112 series Elemental Analyzer at the University of Stellenbosch. e single crystal X-ray crystallography was performed at Rutgers University, USA, using a Bruker SMART CCD Apex-II area-detector
Summary
Cancer is the second leading cause of death globally, with an estimated 1 in 6 deaths, and is responsible for an estimated 9.6 million deaths in 2018 [1]. New strategies like gene therapy are still being developed where genes from donors are inserted into the DNA of a patient to boost recognition of cancerous cells by the body’s diseases fighting mechanisms. E following decade saw these compounds tested for antiviral properties which were confirmed, leading to intense research which eventually culminated to the commercialization of some thiosemicarbazone products under trade names. ® methisazone and Marboran , in the treatment of smallpox [6] Another major step in utilization of these compounds was the publication of the first antitumor tests [7]. E main objectives were to evaluate the tuning of structure-activity relationships vis-a-vis different σ and/or π-donor/acceptor properties of the groups attached to the metal center, their anticancer activities, and their binding modes to DNA. A crystal structure of one of the ligands, L1, is reported here for the first time according to the CCCD database
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