Antioxidant, Cytotoxic Activity and Pharmacokinetic Studies by Swiss Adme, Molinspiration, Osiris and DFT of PhTAD-substituted Dihydropyrrole Derivatives.

BACKGROUND: Pyrrole compounds having a heterocyclic structure are the most researched and biological activities such as antioxidant and anticancer activities. OBJECTIVE: Herein is a first effort to study the significance of heterocyclic compounds to include pyrrole and triazolidine-3,5-dion moiety, on the pharmacokinetic, antioxidant activity and cytotoxic activity on MCF-7 and MCF-12A cell lines. METHOD: The molecular structures of compounds I-XIV were simulated by the theoretical B3- LYP/DFT method. Pharmacokinetic studies of PhTAD-substituted heterocyclic compounds (IXIV) were analyzed to show Lipinski's rules via in-silico methods of Swiss-ADME. The drug likeness calculations were carried out in Molinspiration analyses. Some toxicity risk parameter can be quantified using Osiris. Antioxidant activities determined by DPPH, Fe+2 ions chelating and reducing. Cytotoxic activity measured by MTT and RTCA Results: Compared with the DPPH activity, the metal chelating activity exhibited serious similar antioxidant effects by PhTAD substituted pyrrole compounds. The same compounds showed the highest activity among the two antioxidant activities. The IC50 values of the compounds are in the range of 12 and 290 µM in the MCF-7 cell line. In the MTT and RTCA assays, All compounds showed cytotoxic activity, but about half of the fourteen compounds showed high cytotoxicity. IC50 values of the compounds are in the range of 5 and 54 µM for MTT and range of 1.5 and 44 µM for RTCA. CONCLUSION: Data of the antioxidant and cytotoxic activity of PhTAD-substituted dihydropyrrole- derived compounds in MCF-7 and MCF-12A cell lines confirmed that the compounds are biologically active compound and are notable for anti-cancer researches.

Evaluation of maternal and embryotoxic effects following the treatment of chloral hydrate in Drosophila melanogaster.

Chloral hydrate (CH) is commonly used as a sedative and a hypnotic in pediatric medicine. In this study, the effects of CH on various developmental stages of Drosophila melanogaster were investigated. Different concentrations of CH (0.1; 0.3; 0.5 and 1 mg/mL) were used during development of the flies. Maternal toxicity due to increasing the concentration of CH was observed as a large number of adult flies died. When the F1 progeny of the control and application groups were compared, CH was found to extend the process of metamorphosis and to decrease the total number of offspring. The embryotoxic effects on the offspring and an increase in the number of malformed offspring was identified as depending on feeding. It was found that the difference between the groups was significantly important (p < 0.05).

The use of endemic Iranian plant, Echium amoenum, against the ethyl methanesulfonate and the recovery of mutagenic effects.

In this study, potential genotoxic effects of ethyl methanesulfonate (EMS) that caused mutagenicity in a variety of organisms were tried to resolve by the methanol and chloroform extract of Echium amoenum (EAmet and EAchl) Fisch. & C.A. Mey. from the family of Boraginaceae, which is an endemic plant, and is used as an alternative treatment among public in Iran. Somatic mutation and recombination test with Drosophila wing was used to determine the genotoxic and antigenotoxic effects in our investigations. For this purpose, 3-day-old transheterozygous larvae of mwh/flr(3) genotype of Drosophila melanogaster were used in all our experiments. The larvae were fed chronically on the Drosophila instant medium (DIM) including 1 ppm EMS. However, in another application group, different concentrations (1, 2 and 4 ppm) of EAmet and EAchl were added to DIM including 1 ppm EMS (EMS + EAmet and EMS + EAchl). Then, for the matured individuals, wing preparates were prepared within the mediums that include control group that has only DIM, negative control group that contains dimethyl sulfoxide and application groups in different concentrations that contain EMS, EMS + EAmet and EMS + EAchl. Clone induction frequency for the normal wing phenotype of EMS application group was observed to be 2.00. In the EMS + EAmet application group, the value of 1 ppm EAmet is 1.49, value of 2 ppm EAmet is 1.08 and value of 4 ppm EAmet is 0.72; in the EMS + EAchl application group, the value of 1 ppm is EAchl 1.33, value of 2 ppm EAchl is 0.67 and value of 4 ppm EAchl is 0.56 were determined. This decrease observed between EMS and all application groups in terms of total induction frequency is statistically significant (p < 0.05). These results concluded that chloroform extracts were more effective than the methanol extracts of E. amoenum.

The hazardous effects of three natural food dyes on developmental stages and longevity of Drosophila melanogaster.

Nowadays, food dyes obtained from herbal, animal, microbial and mineral sources are widely used as food additives. In this study, the toxic effects of three different natural food dyes (carmine, turmeric and annatto) on 72 ± 4 h larvae of Oregon-R wild type of Drosophila melanogaster were investigated. For this purpose, four different application doses (50, 75, 100, 125 mg mL(-1)) were chosen by means of preliminary studies. It was determined that larval mortality increased with increasing concentration in the application groups and the toxicity order was carmine > turmeric > annatto. It was observed that the survival rate was highest in the control with 98% and lowest in 125 mg mL(-1) carmine with 16%. In addition, the average lifespan of the adult individuals obtained from third instar larvae was also studied. While the average lifespan was 40.88 ± 1.44 days in the control group, these values were 10.81 ± 0.55-23.90 ± 1.27 days in the carmine group, 15.00 ± 0.80-22.42 ± 1.43 days in the turmeric group and 10.33 ± 1.03-35.68 ± 1.54 days in the annatto group, respectively. According to the obtained results, when both the developmental period from larvae into adults and the lifespan of the developing adults were compared with the control group, the food dyes were found to be toxic and the toxicity order of carmine > turmeric > annatto was identified.

Determination of the effects of genistein on the longevity of Drosophila melanogaster meigen (Diptera; Drosophilidae).

In this study, the effects of genistein on the longevity of Drosophila melanogaster were investigated. The effects of different concentrations of genistein (1, 3, 5 and 10 µM/100 mL medium) were separately administered one by one to female and male populations of D. melanogaster for application groups. In the control group, the maximum life span was determined to be 57 days for ♀♀, 46 for ♂♂. The maximum life span for the lowest (1.0 µL) and highest (10.0 µL) application groups among the adult populations of D. melanogaster subjected to genistein were observed to be 54, 50, 40 and 36 days for ♀♀ and 51, 48, 40 and 33 days for ♂♂. These values indicate a negative correlation (R = 0.513 for ♂♂ and R = 0.509 for ♀♀) between the maximum life span of the application groups and changing genistein concentrations.

Extended longevity of Drosophila melanogaster by water and ethanol extracts of Stachys lavandulifolia.

CONTEXT: Stachyss species have been used as a medicine for centuries throughout the world. Stachys lavandulifolia Vahl. var. lavandulifolia (Lamiaceae) is of interest to researchers because the constituents such as betulinic acid, oleanolic acid, rosmarinic acid, and ursolic acid are similar to other Stachys species commonly used as an alterative in medicinal preparations. OBJECTIVE: The present study investigated the effects of water extract (SLE(w)) and ethanol extract (SLE(e)) obtained from S. lavandulifolia (SLE) on the longevity of Drosophila melanogaster Meigen. MATERIALS AND METHODS: The effects of different concentrations of SLE (Control+DMSO; 4.0; 12.0 and 20.0 µL/100 mL medium) were administered separately to female and male populations of D. melanogaster for control and SLE groups. RESULTS: In all application groups, each population's longevity increased, depending on the concentration of SLE. The mean life-span of the extract groups which are applied with SLE((w)) was determined to be shorter than the extract groups which are applied with SLE((e)). For example, the maximum mean life-span applied with SLE((w)) increased from 31.86 ± 0.92 days to 43.21 ± 1.33 days and the maximum mean life-span applied with SLE((e)) increased from 31.86 ± 0.92 days to 49.62 ± 1.62 days in females. CONCLUSION: These findings demonstrate that the constituents of S. lavandulifolia have great potential as a source for natural health products for D. melanogaster management.