Investigation of Reaction Between Arsenoplatins and Hk Inhibitor – A Pathway for Targeted Delivery
Location
Village Square
Department
Chemistry
Abstract
A century ago, Otto Warburg discovered that cancer cells require significantly more glucose than normal cells and most glucose is fermented to lactate in the process known as “aerobic glycolysis” or the Warburg effect. Although the Warburg effect has been known for an extended period of time, scientists recently explored targeting enzymes involved in glycolysis to suppress cancer growth. Arsenoplatins are potent dual harmacophore anticancer agents with broad anticancer activity. To synthesize derivatives of arsenoplatins that will accumulate more in cancer cells than normal cells and simultaneously target enzymes highly expressed in cancer, we have investigated the reaction between arsenoplatins with 5-thioglucose. 5-thioglucose is a potent inhibitor of hexokinase, a rate-limiting enzyme that catalyzes the first step of glucose metabolism. Hexokinase-2 (HK2) is one of five isozymes, and it is highly expressed in cancer cells and only in a limited number of adult tissues. The reaction of sodium 5-thioglucose salt (NaC6H11O5S) (Na-TG) with arsenoplatin-1 [Pt(μ-NHC(CH3)O)2ClAs(OH)2] (AP-1) is performed in a 1:1 ratio in methanol at 50°C for 1.5 hours. Comparing the frequencies of stretching vibrations of C-O bonds in FT-IR spectra of free sodium 5-thioglucose salt and yellow complex obtained indicates that 5-thioglucose is coordinated to metal and/or metalloid ions. The yellow complex will be further characterized using 1D and 2D NMR and ICP-MS. After fully characterizing the yellow complex, it will be tested in vitro against triple-negative breast and cisplatin-resistant ovarian cancer cell lines.
Faculty Sponsor
Denana Miodragovic, Northeastern Illinois University
Investigation of Reaction Between Arsenoplatins and Hk Inhibitor – A Pathway for Targeted Delivery
Village Square
A century ago, Otto Warburg discovered that cancer cells require significantly more glucose than normal cells and most glucose is fermented to lactate in the process known as “aerobic glycolysis” or the Warburg effect. Although the Warburg effect has been known for an extended period of time, scientists recently explored targeting enzymes involved in glycolysis to suppress cancer growth. Arsenoplatins are potent dual harmacophore anticancer agents with broad anticancer activity. To synthesize derivatives of arsenoplatins that will accumulate more in cancer cells than normal cells and simultaneously target enzymes highly expressed in cancer, we have investigated the reaction between arsenoplatins with 5-thioglucose. 5-thioglucose is a potent inhibitor of hexokinase, a rate-limiting enzyme that catalyzes the first step of glucose metabolism. Hexokinase-2 (HK2) is one of five isozymes, and it is highly expressed in cancer cells and only in a limited number of adult tissues. The reaction of sodium 5-thioglucose salt (NaC6H11O5S) (Na-TG) with arsenoplatin-1 [Pt(μ-NHC(CH3)O)2ClAs(OH)2] (AP-1) is performed in a 1:1 ratio in methanol at 50°C for 1.5 hours. Comparing the frequencies of stretching vibrations of C-O bonds in FT-IR spectra of free sodium 5-thioglucose salt and yellow complex obtained indicates that 5-thioglucose is coordinated to metal and/or metalloid ions. The yellow complex will be further characterized using 1D and 2D NMR and ICP-MS. After fully characterizing the yellow complex, it will be tested in vitro against triple-negative breast and cisplatin-resistant ovarian cancer cell lines.