Synthesis, Structural Characterization, and in vitro Biological Assessment of trans- Platinum (II) Thionate Complexes as Potent Anticancer Agents

Author

Mia AlshamiFollow

Date of Graduation

5-2022

Document Type

Thesis

Degree Name

Bachelor of Science

Degree Level

Undergraduate

Department

Chemistry & Biochemistry

Advisor/Mentor

McIntosh, Matt

Committee Member/Reader

Allison, Neil

Committee Member/Second Reader

Alrubaye, Adnan Ali Khalaf

Committee Member/Third Reader

Sakon, Joshua

Abstract

The content of this thesis has been originally reported in our published paper, “trans-Platinum (II) Thionate Complexes: Synthesis, Structural Characterization, and in vitro Biological Assessment as Potent Anticancer Agents” ChemPlusChem 2019 84, 1525-1535, DOI: 10.1002/cplu.201900394, in which I served as coauthor. Cancer caused 9.6 million deaths in 2018 worldwide, with 18.1 million new diagnoses during that same year.The most widely used metal in anticancer drugs is platinum (Pt), and these drugs are used to treat almost 50% of cancer patients. To optimize drug effectiveness, trans-configured Pt(II) complexes have been introduced as a strategy to potentially overcome the drawbacks that cis-configured Pt(II) have. Also, trans-configured Pt(II) complexes may diminish severe side effects, drug resistance, poor selectivity, and serious toxicity of cisplatin. A series of Pt(II) complexes trans-[Pt(PPh₂allyl)₂(k¹-S-SR)₂], 1, PPh₂allyl = allyldiphenylphosphine, SR = pyridine-2-thiol (Spy, 1a), 5-(trifluoromethyl)-pyridine-2-thiol (SpyCF₃-5, 1b), pyrimidine-2-thiol (SpyN, 1c), benzothiazole-2-thiol (Sbt, 1d), benzimidazole-2-thiol (Sbi, 1e), were synthesized. They were characterized by NMR, HR ESI-MS and X-ray crystallography. These complexes were treated by human cancer cell lines (A549, SKOV3, MCF-7) and shown the promising antitumor effects in comparison with cisplatin. These compounds were showed suitable selectivity between tumorigenic and non-tumorigenic (MCF-10A) cell lines. Analyses of cell cycle progression and apoptosis were conducted for 1a, the best cytotoxic compound, to screen dose/time response and to study the effects of the antiproliferative mechanism. The electrophoresis mobility shift assay was performed to assess the direct interaction of 1a with DNA and the strong genotoxic ability was indicated through comet assay method.

Keywords

antitumor agents, cytotoxicity, metallodrugs, thionates, platinum

Citation

Alshami, M. (2022). Synthesis, Structural Characterization, and in vitro Biological Assessment of trans- Platinum (II) Thionate Complexes as Potent Anticancer Agents. Chemistry & Biochemistry Undergraduate Honors Theses Retrieved from https://scholarworks.uark.edu/chbcuht/29