Cytotoxicity

ABSTRACTProstate cancer is an androgen-dependent disease that responds to established therapies that reduce circulating testosterone levels or inhibit androgen binding to the androgen receptor. This has resulted in the development of a variety of new drugs that target this hormone-regulated transcription factor. Oral enzalutamide drug is a potent androgen receptor antagonist inhibitor for the treatment of castration-resistant prostate cancer, but enzalutamide is classified as BCS class II substances with low aqueous solubility. In recent decades, dendrimers have proven to be effective as solubilizers. Due to their special qualities, dendritic macromolecule is an effective drug solubilizing agent. Therefor the current work is to improve the solubility of enzalutamide by using hydroxy-terminated dendritic macromolecules. The potential of nanoscale hydroxy-terminated dendritic macromolecules TG1.0, TG2.0 and TG3.0 as enzalutamide solubility enhancers was investigated. The effect of concentration and generation of synthesized dendritic macromolecules on enzalutamide solubility was investigated. The FT-IR spectra were used to characterize the formation of complexes between drug molecules and dendritic macromolecules. The experimental results revealed that enzalutamide solubility increased with dendrimer concentration and generation. The cytotoxicity and hemolytic potential of synthesized hydroxy-terminated dendritic macromolecules excelled over commercially available polyamidoamine dendrimers (PAMAM) in a cytotoxicity assay using A-549 lung cancer cell lines. Keywords: Enzalutamide, Cytotoxicity, Dendrimer, Hemolysis, Solubility

ABSTRACTDomperidone (DOM), an antidopaminergic medication, is primarily used as an antiemetic to treat nausea and vomiting caused by a variety of etiologies. It is very insoluble in water and has a poor oral bioavailability of 13-17%. The objective of the current work is to increase domperidone aqueous solubility using nano-structured hydroxy-terminated dendrimers. Dendrimers are distinctive carriers for drug solubilization because of their many special characteristics in terms of size, shape, branching length, and surface functioning. Dendrimers have unique properties that make them potential carriers for many active medicinal compounds due to their structural adaptability. The potential of hydroxy-terminated dendrimers UG1.0, UG2.0, and UG3.0 as solubility enhancers for domperidone was investigated. The effect of concentration and generation of synthesized nano-structured dendritic macromolecules on the solubility of domperidone was studied. The formation of the complexes between domperidone drug molecules and dendrimers was characterized by the FT-IR spectra. The experimental results showed that the solubility of the domperidone was approximately proportional to dendrimer concentration and generation. The water solubility of domperidone has been increased as generation of the hydroxy-terminated dendrimer. Cytotoxicity assay using A-549 lung cancer cell lines and hemolysis results revealed that synthesized dendritic macromolecules are more biocompatible than commercially available polyamidoamine dendrimers (PAMAM). Keywords: Antiemetic, Cytotoxicity, Dendrimer, Domperidone, Hemolysis, Phase solubility.

ABSTRACTHerein we report an exploratory study based on the cytotoxicity and antiproliferative activity of four previously synthesized coumarins derivatives (compounds 1a-d). The cytotoxic effect of the compounds was assessed on mononuclear cells, which were obtained from blood samples of healthy donors and measured by XTT method. The antiproliferative activity experiments were developed using HeLa, CaSKi and SiHa cervical cancer cell lines, and was evaluated by the MTT assay. In every single experiment, Cisplatin as internal control was employed. The cytotoxic assessment revealed that the four compounds did not significantly affect the viability on normal cells, whereas the antiproliferative activity on cancer cells was variable, according to the substituent located at position 3 of the coumarin core. It is worth mentioning that compound 1c, compared with the other products, presented a remarkable effect against CaSKi cell line, likewise 1d but in HeLa cells. These findings suggest that there is a relationship between biological activity and the alkoxycarbonyl chain since this is the only structural difference among the four tested compounds. The results lead to conclude that butyl group which is the substituent in compound 1d, was the key element in the antiproliferative effect presented by the molecule against SiHa, CaSKi and HeLa cell lines. Keywords: Coumarins, Tumor cells, Mononuclear cells, Cis-Platin, Cytotoxicity, MTT.

ABSTRACTBauhinia variegata (Family: Fabaceae) is well-known medicinal plant used from the ancient era to till date for their medicinal values. The powerful biological activities as exhibited by plant flavonoids posed the need of determining their contents in B. variegata stem bark. In view of its wide use and its chemical compositions, this study was aimed at examining and comparative analysis of the antioxidant and anticancer activities of the different extracts of stem bark. Antioxidant activity of extracts was expressed as percentage of DPPH, super oxide and nitric oxide free radicals inhibition and expressed asIC50 values (?g/mL). Methanolic extracts of B. variegata showed the highest amount of and ?avonoid contents and reducing capacity whereas, chloroform and dichloromethane extracts of B. variegata showed pronounced cytotoxic effect against HCT-116, A549 and ethyl acetate extracts showed pronounced cytotoxic effect against Ovcer-5 human cancer cell lines. The order of antioxidant activity in B. variegata extracts displayed from higher to lower level as methanol, hydro-alcoholic, ethyl acetate, chloroform, dichloromethane and n-hexane extracts of stem bark of B. variegata. Commercial standards were taken as control showed highest antioxidant power in the present study. Chemical components of B. variegata have good antioxidant capacities and this species could be used as a potential source of new natural antioxidants. Keywords: Antioxidant; Bauhinia variegata; Cytotoxicity; Stem bark extract; Total flavonoids.

The objective of this research work was comparative evaluation of in vitro cytotoxicity of troglitazone, rosiglitazone and pioglitazone in HepG2 cells. Briefly, the HepG2 cells were exposed to multiple concentrations (3.125–100 µM) of three drugs (troglitazone, rosiglitazone and pioglitazone) for 12 h, 24 h and 48 h. At the end of each treatment period, cytotoxicity was determined using multiple end points such as 3-[4,5-imethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, neutral red assay and lactate dehydrogenase leakage assay. Troglitazone showed time and concentration dependent cytotoxicity in all three end points with evident cytotoxic effects being observed at 50 and 100 µM concentrations. MTT assay showed higher cytotoxicity and early onset compared to neutral red and lactate dehydrogenase leakage assay at all time points. There was no cytotoxicity observed for rosiglitazone at all tested concentrations up to 100 µM. Similarly, pioglitazone also did not affect the viability of HepG2 cells up to the concentration of 50 µM however some cytotoxicity was noted at 100 µM concentration which could be partly attributed to the precipitation of test compound noted at 100 µM concentration after addition to the culture medium. The results from this research work indicated that among the three drugs tested in this study, only troglitazone induced time and concentration dependent toxicity in the HepG2 cells in all three end points with MTT assay being the most sensitive assay.