Abstract 2000 Anti-Cancer Activity of Novel Cobalt, Copper, Manganese, Iron, and Silver Benzothiazole and Benzoimmidazole Complexes

In the United States, pancreatic carcinoma stands as the fourth leading cause of cancer-related deaths for both genders. It is responsible for a little over 7% of all cancer-related fatalities and approximately 3% of all cancer cases. Despite the advancements in medical therapies and surgical techniques, the 5-year survival rate for this disease remains below 2%, and the median survival time after diagnosis is less than six months. Regrettably, several chemotherapeutics exhibit adverse side effects and fail to treat the patient long-term, thereby necessitating the pursuit of novel, effective, and non-toxic therapies. The present research aims to examine the anti-cancer effectiveness of nine synthetic compounds 2- (2-benzothiazolyl) -5-methoxyphenol (2HA), Tri (2- (2-benzothiazolyl) -5-methoxyphenol) cobalt (III) (2HA-Co), Di (2- (2-benzothiazolyl) -5-methoxyphenol) copper (II) (2HA-Cu), (2- (2-benzothiazolyl) -5-methoxyphenol) silver (I) (2HA-Ag), 1, 3-Dihydro-5- (E) -[ (2-hydroxyphenyl) methyleneamino]-2H-benzimidazole-2-thione (J1), Di (1, 3-Dihydro-5- (E) -[ (2-hydroxyphenyl) methyleneamino]-2H-benzimidazole-2-thione) manganese (III) (MnJ1), Di (1, 3-Dihydro-5- (E) -[ (2-hydroxyphenyl) methyleneamino]-2H-benzimidazole-2-thione) iron (III) (FeJ1), Di (1, 3-Dihydro-5- (E) -[ (2-hydroxyphenyl) methyleneamino]-2H-benzimidazole-2-thione) cobalt (III) (CoJ1), Di (1, 3-Dihydro-5- (E) -[ (2-hydroxyphenyl) methyleneamino]-2H-benzimidazole-2-thione) nickel (III) (NiJ1) on the Mia-Paca-2 cell line derived from human pancreatic ductal adenocarcinoma. Dimethyl sulfoxide (DMSO) was utilized as a solvent to prepare the nine synthetic compounds 2- (2-benzothiazolyl) -5-methoxyphenol (2HA), Tri (2- (2-benzothiazolyl) -5-methoxyphenol) cobalt (III) (2HA-Co), Di (2- (2-benzothiazolyl) -5-methoxyphenol) copper (II) (2HA-Cu), (2- (2-benzothiazolyl) -5-methoxyphenol) silver (I) (2HA-Ag), 1, 3-Dihydro-5- (E) -[ (2-hydroxyphenyl) methyleneamino]-2H-benzimidazole-2-thione (J1), Di (1, 3-Dihydro-5- (E) -[ (2-hydroxyphenyl) methyleneamino]-2H-benzimidazole-2-thione) manganese (III) (MnJ1), Di (1, 3-Dihydro-5- (E) -[ (2-hydroxyphenyl) methyleneamino]-2H-benzimidazole-2-thione) iron (III) (FeJ1), Di (1, 3-Dihydro-5- (E) -[ (2-hydroxyphenyl) methyleneamino]-2H-benzimidazole-2-thione) cobalt (III) (CoJ1), Di (1, 3-Dihydro-5- (E) -[ (2-hydroxyphenyl) methyleneamino]-2H-benzimidazole-2-thione) nickel (III) (NiJ1). Mia-Paca-2 cells were cultured overnight and then treated for 48h with 1 μM and 10 μM of each compound using 100 μM paclitaxel and DMSO as controls. The anti-cancer activity was examined by measuring the cell using MTT (3-4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide). The result for each treatment was compared to the DMSO control using one-way ANOVA statistical analysis with a Dunnett post-analysis for multiple comparisons. Di (2- (2-benzothiazolyl) -5-methoxyphenol) copper (II) (2HA-Cu) showed a reduction in cell viability at 1 μM, while 2HA, 2HA-Cu, 2HA-Ag, FeJI, CoJI, and NiJI exhibited a decrease in cell viability at 10 μM (p-value<0. 05). These findings show that these six novel synthetic compounds (2HA, 2HA-Cu, 2HA-Ag, FeJI, CoJI, and NiJI) reduce the cell viability of pancreatic cancer Mia-Paca-2 cells, indicating that these compounds may be used as potential treatments of the disease. Of particular interest is Di (2- (2-benzothiazolyl) -5-methoxyphenol) copper (II) (2HA-Cu) that exhibits the most potent anti-cancer effect. Importantly, these compounds need to be studied further to determine the half-maximal inhibitory concentrations (IC50) and the mechanism of action. I acknowledge the School of Graduate Studies and Chemistry Department at Western Illinois University for the Graduate Student Research and Professional Development Fund.