Anticancer activities and mechanism of action of 2 novel metal complexes, C16H34N8O5Ag2Cd and C11H16N7O2Ag3Ni

Abstract

IntroductionCancer is considered the second most common disease causing death (Tuncer, 2008). It is estimated that 19.3 million new cancer cases will be detected per year by 2025. The incidence, morbidity, and mortality of cancer are expected to be much higher in developing countries such as Turkey. Efforts to cure cancer or reduce its occurrence will be significantly important (Tuncer, 2008).Although many anticancer drugs have been used to treat cancer, they have some limitations, such as side effects, tumor specificity, and tumor cell resistance (Roche, 2002). Therefore, new anticancer drug candidates with few or no side effects need to be developed as alternatives to current chemotherapeutic drugs. Metals and metal compounds have been used in medicine as antiprotozoal, antiulcer, antiarthritic, antimalarial, antimicrobial, and anticancer drugs (Avendańo, 2008). Nowadays, the application of metal complexes in medicine is being investigated very extensively. Thati et al. (2007) reported that silver complexes of coumarin derivatives possess anticancer activity against certain types of cancer. Zhu et al. (2003) reported that silver carboxylate dimers exert anticancer activity against human carcinoma cells. The phosphine Abstract: The discovery of anticancer activity in cisplatin triggered the development of novel drugs containing metals such as platinum or ruthenium. Extremely diverse structural chemistry and the interaction of metal complexes with biomolecules resulted in the exploration of novel metal complexes with drug potential. In the present study, the anticancer and cytotoxic activities and the mechanisms of action were investigated for C 16 H 34 N 8 O 5 Ag 2 Cd (AN1) and C 11 H 16 N 7 O 2 Ag 3 Ni (AN7), 2 newly synthesized dicyanidoargentate(I) complexes. The anticancer and cytotoxic activities of AN1 and AN7 on several cancer cell lines were tested by cell proliferation and cytotoxic activity assays, respectively. The apoptotic and replication inhibitory potentials of the compounds were investigated using terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL) and DNA topoisomerase inhibition assays. AN1 and AN7 showed significant (P < 0.05) anticancer activity and lower cytotoxicity against all cell lines tested. The TUNEL assay results indicated that AN1 and AN7 may inhibit cell proliferation by inducing apoptosis. The compounds showed very significant DNA topoisomerase I inhibitory activity. Based on the results, it is suggested that compounds AN1 and AN7 are potential anticancer drug candidates.

Synthesis and Biological Evaluation of Novel 1‐(4‐(Hydroxy(1‐oxo‐1,3‐dihydro‐2H‐inden‐2‐ylidene)methyl)phenyl)‐3‐phenylurea Derivatives

“…In order to examine the cell proliferation in the study, the BrdU Cell proliferation ELISA kit was used . The method is based on the measurement of BrdU (5‐Bromo‐2′‐deoxy‐uridine) bound to cellular DNA during DNA synthesis using anti‐BrdU antibody.…”

“…In order to examine the cell proliferation in the study, the BrdU Cell proliferation ELISA kit was used. [56] The method is based on the measurement of BrdU (5-Bromo-2 0 -deoxy-uridine) bound to cellular DNA during DNA synthesis using anti-BrdU antibody. Plates of 96 were seeded as 3 9 10 3 cells and incubated on 24 h. The BrdU labeling reagent prepared by adding BrdU: DMEM (1: 100) was pipetted in 20 ll wells and incubated for 4 h. Solution was discharged and FixDenate solution was added to make 100 ll/well and incubated at r.t. for 45 min.…”

Cellular toxicity and biological activities of honey bee (Apis mellifera L.) venom

“…The final volume of the wells was adjusted to 200 µL by supplemented DMEM and cells were incubated at 37 °C with 5% CO 2 for overnight. The rest of the proliferation assay was performed as described as in Aydin, et al (17).…”

“…A DNA fragmentation activity of the BV was measured by using DNA laddering assay according to the method of Gong et al (18) with some modifications as described in Aydin, et al (17).…”

Six coordination compounds: mode of cytotoxic action and biological evaluation

“…Research efforts on the development of novel anticancer agents play an important role in the current treatment process for cancer. These investigations are focused on the goal to find effective drugs without side effects or drug resistance [2][3][4][5][6][7]. It is known that the metal complexes including copper, gold, germanium, iron, that has a vital role in the normal functioning of the nervous system.…”