Current Pharmaceutical Research on the Significant Pharmacophore Mannich bases in Drug Design.

A multitude of distinct Mannich bases have been synthesized and evaluated as potential therapeutics for a wide variety of diseases and medical conditions, either in the form of prodrugs or as molecules that trigger a biological response from specific targets. The Mannich reaction has been utilized to enhance the biological activity of numerous compounds, resulting in notable progress in various areas such as anticonvulsant, antimalarial, anticancer, anti-inflammatory, antiproliferative, antibacterial, antimicrobial, antitubercular, antiprotozoal, topoisomerases I and II inhibition, α-glucosidase inhibition, carbonic anhydrase inhibition, as well as research related to anti-Alzheimer's disease and anti-Parkinson's disease. Bioactive semisynthetic Mannich bases derived from natural compounds such as chalcone, curcumin, and thymol have also been identified. Pharmaceutical compounds characterized by low solubility may encounter challenges related to their oral bioavailability, half-life, distribution within tissues, rapid metabolism, toxicity, and various other relevant variables. Mannich bases have the ability to undergo protonation under physiological circumstances, facilitating interactions between ligands and receptors, and enhancing their solubility in water. The experimental findings indicate that the solubility of Mannich base prodrugs is higher compared to that of the parent compound. The use of the multicomponent Mannich reaction has been established as a valuable synthetic methodology for the construction of multifunctional compounds through the application of diverse synthetic strategies under varying reaction conditions. The continuous investigation of synthetic techniques for Mannich reactions involves several approaches, such as employing protocols in aquatic environments, utilizing catalysts that are both biodegradable and reusable, exploring the use of ionic liquids, investigating solvent-free and/or catalyst-free media, and exploring reaction conditions involving microwave and ultrasound irradiation. Consequently, the Mannich reaction has emerged as a powerful technique in the field of medicinal chemistry. It is utilized for the creation of new chemical compounds that possess diverse and attractive biologic features. Additionally, this reaction is employed to alter the physicochemical properties of a potential drug candidate, thereby influencing its bioavailability, efficacy, and pharmacological activity. Due to their favorable bioactivities and synthesis techniques, Mannich bases remain a subject of ongoing attention in the field of medicinal/pharmaceutical chemistry.

Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuries.

According to population-based studies, lung cancer is the prominent reason for cancer-related mortality worldwide in males and is also rising in females at an alarming rate. Sorafenib (SOR), which is approved for the treatment of hepatocellular carcinoma and renal cell carcinoma, is a multitargeted protein kinase inhibitor. Additionally, SOR is the subject of interest for preclinical and clinical trials in lung cancer. This study was designed to assess in vivo the possible effects of sorafenib (SOR) in diethylnitrosamine (DEN)-induced lung carcinogenesis and examine its probable mechanisms of action. A total of 30 adult male rats were divided into three groups (1) control, (2) DEN, and (3) DEN + SOR. The chemical induction of lung carcinogenesis was performed by injection of DEN intraperitoneally at 150 mg/kg once a week for two weeks. The DEN-administered rats were co-treated with SOR of 10 mg/kg by oral gavage for 42 alternate days. Serum and lung tissue samples were analyzed to determine SRY-box transcription factor 2 (SOX-2) levels. The tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß) levels were measured in lung tissue supernatants. Lung sections were analyzed for cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) histopathologically. In addition, cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) were analyzed by immunohistochemistry and immunofluorescence methods, respectively. SOR reduced the level of SOX-2 that maintenance of cancer stemness and tumorigenicity, and TNF-α and IL-1ß levels. Histopathological analysis demonstrated widespread inflammatory cell infiltration, disorganized alveolar structure, hyperemia in the vessels, and thickened alveolar walls in DEN-induced rats. The damage was markedly reduced upon SOR treatment. Further, immunohistochemical and immunofluorescence analysis also revealed increased expression of COX-2 and JNK expression in DEN-intoxicated rats. However, SOR treatment alleviated the expression of these inflammatory markers in DEN-induced lung carcinogenesis. These findings suggested that SOR inhibits DEN-induced lung precancerous lesions through decreased inflammation with concomitant in reduced SOX-2 levels, which enables the maintenance of cancer stem cell properties.

Short-term tourism alters abundance, size, and composition of microplastics on sandy beaches.

Microplastics have become a global threat to sandy beach ecosystems. To efficiently manage this threat, potential sources of microplastics should be deeply understood, which requires direct evidence as this is always a challenging task. Previous studies have reported various sources; however, the topic still needs attention to identify other potential sources of microplastics on sandy shores. Therefore, the abundance, size, color, shape, and polymer type of microplastics on nine sandy shores of the Turkish Coast of the Black Sea were examined before and after the regular tourism season to understand whether short-term tourism might be an important source. A total of 3402 microplastic items from 270 sand samples were obtained and examined. Both the abundance and the average size of the microplastics increased after the tourism season associated with the potential number of visitors and beach cleaning efforts. Further, the color, shape, and polymer type of microplastics varied between sampling times. Beach cleaning seemed to be an efficient way to minimize the adverse effect of short-term tourism influence. This study clearly identifies short-term tourism as an important source of microplastics on sandy shores and beach cleaning as an important tool to minimize microplastic abundance. The results of this study are important insights into current literature by identifying another source of microplastics on sandy shores, which should be useful for the potential management actions to reduce the harm of these global pollutants.

Use of measured accelerations from a passenger rail car to evaluate ride quality and track roughness - A case study.

Increasing traffic and speeds on passenger rail lines, and a short season for maintenance work, have motivated the industry to find new methods to assess the condition of existing infrastructure and determine where upgrades are required. In this study, acceleration data from the car body and axle boxes of a revenue car over 92 km of a Canadian passenger rail route in Ontario were collected for two purposes: first, to apply weighted filtering method according to ISO 2631-1997 standard as a technique to determine the locations which highly impact the ride quality and to investigate the effect of type of track features and speed on the ride quality; second, a new analytical method called the envelope of acceleration was applied to use the recorded accelerations to evaluate the alignment and surface roughness along the track. Since the alignment and surface roughness values are always positive and are calculated over a specified length (e.g. 9.5 m, 18.9 m, 38 m) an envelope technique was employed which uses spline interpolations over local maxima of the absolute magnitude of accelerations at every separated n samples corresponding to best fit with track roughness. The regression analysis between the envelope of accelerations and alignment and surface roughness presented a meaningful correlation and showed the applied method is a promising analytical technique to indicate rough sections of the track. The limitations to the application of envelope of acceleration are also discussed.

Diffusion-Weighted Imaging of Brain Metastasis: Correlation of MRI Parameters with Histologic Type.

AIM: To compare the diffusion properties of brain metastases as imaging biomarkers in various types of tumours, to determine their histology and origin. MATERIAL AND METHODS: Magnetic Resonance Imaging (MRI) and diffusion-weighted imaging (DWI) were used to retrospectively study the data of 143 patients suffering from brain metastases. Four categories of primary tumours with metastases to the brain were included: lung carcinoma (n=102, 71.3%); breast carcinoma (n=27, 18.8%); colon carcinoma (n=8, 5.6%); and others (n=6, 4.2%). The Apparent Diffusion Coefficient (ADCmin ) values, as well as the normalised ADC ratio (nADC), were determined. The lesions on the DWI were categorised as follows: type 1, with negative findings on DWI; type 2, which were isointense with the normal cortical grey matter; type 3, which were hyperintense compared to the normal cortical grey matter. RESULTS: The diffusion type, mean ADCmin, and mean nADC showed statistically significant differences in different types of metastases. In the subgroup analysis, it was found that type 3 was the diffusion type found most extensively in the brain metastases of small cell carcinoma (SCLC) (n=52, 65.8%, p < 0.000). Furthermore, the mean ADCmin and nADC values were the least for the brain metastases of the SCLC (552.0 ± 134.2 and nADC = 0.8 ± 0.1, p < 0.000, respectively). The value of the mean ADCmin was low in the human epidermal growth factor receptor 2 (HER-2) negative groups than in the HER-2 positive groups at 786.8 ± 299.1 vs 844.8 ± 141.3 (p < 0.006). CONCLUSION: Our findings indicated that there is a correlation between diffusion parameters as imaging biomarkers of the solid component of brain metastases of primary tumours and the tumour histology.

Monoamine Oxidase (MAO) as a Potential Target for Anticancer Drug Design and Development.

Monoamine oxidases (MAOs) are oxidative enzymes that catalyze the conversion of biogenic amines into their corresponding aldehydes and ketones through oxidative deamination. Owing to the crucial role of MAOs in maintaining functional levels of neurotransmitters, the implications of its distorted activity have been associated with numerous neurological diseases. Recently, an unanticipated role of MAOs in tumor progression and metastasis has been reported. The chemical inhibition of MAOs might be a valuable therapeutic approach for cancer treatment. In this review, we reported computational approaches exploited in the design and development of selective MAO inhibitors accompanied by their biological activities. Additionally, we generated a pharmacophore model for MAO-A active inhibitors to identify the structural motifs to invoke an activity.

Inverse Filtering for Frequency Identification of Bridges Using Smartphones in Passing Vehicles: Fundamental Developments and Laboratory Verifications.

This paper puts forward a novel methodology of employing inverse filtering technique to extract bridge features from acceleration signals recorded on passing vehicles using smartphones. Since the vibration of a vehicle moving on a bridge will be affected by various features related to the vehicle, such as suspension and speed, this study focuses on filtering out these effects to extract bridge frequencies. Hence, an inverse filter is designed by employing the spectrum of vibration data of the vehicle when moving off the bridge to form a filter that will remove the car-related frequency content. Later, when the same car is moving on the bridge, this filter is applied to the spectrum of recorded data to suppress the car-related frequencies and amplify the bridge-related frequencies. The effectiveness of the proposed methodology is evaluated with experiments using a custom-built robot car as the vehicle moving over a lab-scale simply supported bridge. Nine combinations of speed and suspension stiffness of the car have been considered to investigate the robustness of the proposed methodology against car features. The results demonstrate that the inverse filtering method offers significant promise for identifying the fundamental frequency of the bridge. Since this approach considers each data source separately and designs a unique filter for each data collection device within each car, it is robust against device and car features.

New phenolic Mannich bases with piperazines and their bioactivities.

In this study, new Mannich bases, 2-(4-hydroxy-3-methoxy-5-((substitutedpiperazin-1-yl)methyl)benzylidene)-2,3-dihydro-1H-inden-1-one (1, 2, 4, 5, 8), 2-(3-((substituted)piperazin-1-yl)methyl)-4-hydroxy-5-methoxybenzylidene)-2,3-dihydro-1H-inden-1-one (3, 6, 7) were synthesized with the reaction of vanilin derived chalcone compound (2-(4-hydroxy-3-methoxybenzylidene)indan-1-one), paraformaldehyde and suitable amine in 1:1.2:1 mol ratios. Amine part was changed as N-methylpiperazine (1), N-phenylpiperazine (2), N-benzylpiperazine (3), 1-(2-methoxyphenyl)piperazine (4), 1-(3-methoxyphenyl)piperazine (5), 1-(2-fluorophenyl)piperazine (6), 1-(4-fluorophenyl)piperazine (7), and 1-(3-trifluoromethyl)phenyl piperazine (8). Compounds were evaluated in terms of cytotoxic/anticancer and CA inhibitory effects. According to the results obtained, the compounds 2 and 8 had the highest potency selectivity expression (PSE) values (60.6 and 19.2, respectively). On the other hand, the compounds 3 (Ki = 209.6 ±â€¯70.2 pM) and 5 (Ki = 342.66 ±â€¯63.72 pM) had the lowest Ki values in CA inhibition experiments towards hCA I and hCA II, respectively. In conclusion, the compounds 2 (with cytotoxic/anticancer activity), 3 (with hCA I inhibiting activity) and 5 (with hCA II inhibiting activity) can be leading compounds of the study for further designs and evaluations.

Oxidative stress before and after surgery in benign prostatic hyperplasia patients.

The aim was to assess oxidative stress in benign prostatic hyperplasia patients and also to evaluate the effect of operation in late (60 days) post-operative period. This study was conducted with 16 patients with benign prostatic hyperplasia and 16 healthy subjects. Serum malondialdehyde, blood 8-hydroxy-2'-deoxyguanosine/deoxyguanosine, erythrocyte superoxide dismutase, serum total coenzyme Q10 and coenzyme Q10 levels were measured. Independent samples t test was used to analyse the differences between control group and patients, while paired t test was used to analyse the differences between pre-operative and post-operative periods. Malondialdehyde and total coenzyme Q10 levels were lower in patients, while 8-hydroxy-2'-deoxyguanosine/deoxyguanosine level was increased. However, superoxide dismutase activity and coenzyme Q10 levels did not differ. After 60 days of operation, 8-hydroxy-2'-deoxyguanosine/deoxyguanosine and superoxide dismutase activity decreased, while total coenzyme Q10 level increased. However, malondialdehyde and coenzyme Q10 levels were not affected. The international prostate symptom scores of the patients were also decreased after the operation. The results suggest that blood 8-hydroxy-2'-deoxyguanosine/deoxyguanosine level may reflect the oxidative stress better than the malondialdehyde level, and surgical operation attenuates the oxidative stress in late post-operative period in benign prostatic hyperplasia patients.

Burrowing behavior and burrowing energetics of a bioindicator under human disturbance.

Bioindicator species are extensively used for rapid assessment of ecological changes. Their use commonly focuses on changes in population abundance and individual sizes in response to environmental change. These numerical and demographic shifts likely have behavioral and physiological mechanistic drivers that, if understood, could provide additional insights into the use of these species as bioindicators of habitat health.The Atlantic ghost crab, Ocypode quadrata, is a global bioindicator species of human disturbance on sandy shores. Individual size and population abundance of O. quadrata decline dramatically at sites with human disturbance, and the causes of this phenomenon remain unclear.Here, we test the hypothesis that individual and population-level changes at disturbed sites reflect changes in burrowing behavior and energetics. Specifically, we examine whether or not the burrowing behavior (e.g., burrow fidelity and longevity) of O. quadrata changes because of human disturbance. We also examine energy required for burrowing by O. quadrata across different levels of human disturbance.We show that O. quadrata have the highest burrow fidelity and longevity at sites with low level of human impact, and weakest burrow fidelity and longevity at pristine sites. O. quadrata reduce the burrowing energy allocation by manipulating the burrow dimension and increasing the burrow longevity even under low levels of human disturbance.Overall, this study shows that human disturbances not only change the behavior of organisms, but also shift energetic balance. Our results support the use of a bioenergetic approach to better understand how human disturbances influence natural populations, and the specific use of this approach with this bioindicator species.

Reactive Oxygen Species: the Dual Role in Physiological and Pathological Conditions of the Human Body.

Reactive oxygen species (ROS) are well-known for playing a dual role as destructive and constructive species. Indeed, ROS are engaged in many redox-governing activities of the cells for the preservation of cellular homeostasis. However, its overproduction has been reported to result in oxidative stress, which is considered as a deleterious process, and is involved in the damage of cell structures that causes various diseased states. This review provides a concise view on some of the current research published in this topic for an improved understanding of the key roles of ROS in diverse conditions of health and disease. Previous research demonstrated that ROS perform as potential signaling molecules to control several normal physiological functions at the cellular level. Additionally, there is a growing body of evidence supporting the role of ROS in various pathological states. The binary nature of ROS with their profitable and injurious characteristics indicates the complexities of their specific roles at a biological compartment and the difficulties in establishing convenient intervention procedures to treat ROS-related diseases.

Ecological and evolutionary implications of allometric growth in stomach size of brachyuran crabs.

Individual characteristics often scale allometrically with organismal body size and the form of this scaling can be influenced by ecological and evolutionary factors. Examining the specific form of this scaling can therefore yield important insights into organismal ecology and evolution and the ability of organisms to respond to future environmental changes. We examine the intraspecific allometric scaling of stomach volume with body mass for 17 species of brachyuran crabs. We also examine how this scaling is influenced by dietary strategy, maximum body size, and activity level, all while controlling for phylogenetic relationships between the species. We show that the slope and intercept of the allometric scaling relationships vary across species and are influenced by all three ecological factors examined here, as well as by evolutionary relationships. These results highlight potential divergent strategies in stomach growth taken by different groups of crabs and highlight potential limitations that may be imposed on the ability of this group of organisms to respond to warming trends expected with climate change.

Synthesis and Cytotoxicities of New Azafluorenones with Apoptotic Mechanism of Action and Cell Cycle Analysis.

BACKGROUND: In this study, new azafluorenones, 4-(4-fluorophenyl)-2-(4-substitutedphenyl)-5Hindeno[ 1,2-b] pyridin-5-one, I1-I8 were synthesized and chemical structures were elucidated by spectral analysis. All compounds were reported for the first time here. METHOD: Compounds were tested in terms of cytotoxicity. They were found as cytotoxins/anticancer compounds. RESULTS: It was found that the lead compounds of the series were I5 and I8 according to SI, TS, PSE calculations. When PSE values were considered, compound I5 having chlorine had the highest PSE value of 126.4. Second highest PSE value of 50.5 belonged to I8, which had thiophene ring in its chemical structure. I8 as a representative compound of the series was forwarded to cell cycle analysis. I8 arrested S phase of the cell cycle and lead to apoptosis by inducing PARP cleavage suggesting that at least one of the mechanisms of cytotoxic action of the series was apoptosis. CONCLUSION: It was clearly demonstrated that compound I8 can induce early apoptosis at a concentration of 5 µM. The compounds I5 and I8 can be considered as lead compounds of the series with the highest SI, TS, PSE values for further studies.

Anticancer effects of new dibenzenesulfonamides by inducing apoptosis and autophagy pathways and their carbonic anhydrase inhibitory effects on hCA I, hCA II, hCA IX, hCA XII isoenzymes.

In this study, new dibenzensulfonamides, 7-9, having the chemical structure 4,4'-(5'-chloro-3'-methyl-5-aryl-3,4-dihydro-1'H,H-[3,4'-bipyrazole]-1',2-diyl)dibenzenesulfonamide were synthesized in five steps to develop new anticancer drug candidates. Their chemical structures were confirmed by 1H NMR, 13C NMR and HRMS spectra. Cytotoxicities of the dibenzensulfonamides were investigated towards HCC1937, MCF7, HeLa, A549 as tumor cell lines and towards MRC5 and Vero as non-tumor cells. Carbonic anhydrase (CAs, EC 4.2.1.1) inhibitory effects of the dibenzensulfonamides 7-9 were also evaluated on the cytosolic human (h) hCA I and II and the tumor-associated hCA IX and XII isoenzymes. Results indicate that both 7 and 8 induced cleavage of poly (ADP ribose) polymerase (PARP), activation of caspases -3, -7 and -9 which are the hallmarks of apoptosis. Meanwhile both compounds induced autophagy in HCC1937 cells which is shown by enhanced expression of LC3 and decreased level of p62 protein. The compounds tested were also effectively inhibited tumor-associated hCA IX and hCA XII isoenzymes in the range of 20.7-28.1 nM and 4.5-9.3 nM, respectively.

Curcumin analogue 1,5-bis(4-hydroxy-3-((4-methylpiperazin-1-yl)methyl)phenyl)penta-1,4-dien-3-one mediates growth arrest and apoptosis by targeting the PI3K/AKT/mTOR and PKC-theta signaling pathways in human breast carcinoma cells.

Recent developments in the literature have demonstrated that curcumin exhibit antioxidant properties supporting its anti-inflammatory, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Despite the valuable findings of curcumin against different cancer cells, the clinical use of curcumin in cancer treatment is limited due to its extremely low aqueous solubility and instability, which lead to poor in vivo bioavailability and limited therapeutic effects. We therefore focused in the present study to evaluate the anti-tumor potential of curcumin analogues on the human breast carcinoma cell lines MDA-MB-231 and MCF-7, as well as their effects on non-tumorigenic normal breast epithelial cells (MCF-10). The IC50 values of curcumin analogue J1 in these cancer cell lines were determined to be 5 ng/ml and 10 ng/ml, in MDA-MB-231 and MCF-7 cells respectively. Interestingly, at these concentrations, the J1 did not affect the viability of non-tumorigenic normal breast epithelial cells MCF-10. Furthermore, we found that J1 strongly induced growth arrest of these cancer cells by modulating the mitochondrial membrane potentials without significant effect on normal MCF-10 cells using JC-1 staining and flow cytometry analysis. Using annexin-V/PI double staining assay followed by flow cytometry analysis, we found that J1 robustly enhanced the induction of apoptosis by increasing the activity of caspases in MDA-MB-231 and MCF-7 cancer cells. In addition, treatment of breast cancer cells with J1 revealed that, in contrast to the expression of cyclin B1, this curcumin analogue vigorously decreased the expression of cyclin A, CDK2 and cyclin E and subsequently sensitized tumor cells to cell cycle arrest. Most importantly, the phosphorylation of AKT, mTOR and PKC-theta in J1-treated cancer cells was markedly decreased and hence affecting the survival of these cancer cells. Most interestingly, J1-treated cancer cells exhibited a significant inhibition in the activation of RhoA followed by reduction in actin polymerization and cytoskeletal rearrangement in response to CXCL12. Our data reveal the therapeutic potential of the curcumin analogue J1 and the underlying mechanisms to fight breast cancer cells.

Impacts of human disturbance on ghost crab burrow morphology and distribution on sandy shores.

Ghost crabs have been widely used as a bio-indicator species of human impacts on sandy beaches to obtain reliable biological data for management and conservation purposes. Ghost crab population densities and individual sizes decline dramatically under human pressure. However, distribution within a beach and the factors that determine this distribution of ghost crabs is still an open question. These factors may provide valuable information for understanding human impacts on sandy beaches. Here we examine ghost crab burrows on 20 sandy beaches of South Carolina, USA under various levels of human impacts to understand the response in terms of spatial distribution of this species to human impacts. We also examine the burrow characteristics and environmental properties of the burrows to determine whether these factors alter burrow characteristics. We show that crabs on heavily impacted beaches altered their spatial distribution to mostly occupy the edges of impacted beaches. Further, this change in spatial distribution was influenced by the size distribution of the population on a beach (i.e. larger individuals occupy upper parts on the beaches). We also found that ghost crabs altered the morphology of their burrows on heavily impacted beaches. Ghost crabs create deeper, steeper and smaller burrows under human impacts. These patterns were also influenced by physical characteristics of the beach. Our results suggest that human impacts can directly influence the spatial distribution of ghost crab populations within a beach and therefore sampling at upper parts of the beaches overestimates the population density and individual sizes. Our results support the use of ghost crabs as indicator species in effective beach management, but suggest that assessments would benefit from examining the morphology and distribution of burrows as opposed to simply using burrow counts to assess the health of sandy shores.

Microwave-assisted synthesis and bioevaluation of new sulfonamides.

In this study, 4-[5-(4-hydroxyphenyl)-3-aryl-4,5-dihydro-1H-pyrazol-1-yl]benzenesulfonamide derivatives (8-14) were synthesized for the first time by microwave irradiation and their chemical structures were confirmed by 1H NMR, 13C NMR and HRMS. Cytotoxic activities and inhibitory effects on carbonic anhydrase I and II isoenzymes of the compounds were investigated. The compounds 9 (PSE = 4.2), 12 (PSE = 4.1) and 13 (PSE = 3.9) with the highest potency selectivity expression (PSE) values in cytotoxicity experiments and the compounds 13 (Ki = 3.73 ± 0.91 nM toward hCA I) and 14 (Ki = 3.85 ± 0.57 nM toward hCA II) with the lowest Ki values in CA inhibition studies can be considered as leader compounds for further studies.

Synthesis and Cytotoxic Activities of Difluoro-Dimethoxy Chalcones.

BACKGROUND: Although anticancer chemotherapeutics are available in markets, side effects related to the drugs in clinical use lead to researchers to investigate new drug candidates which are more safe, potent and selective than others. Chalcones are popular with their anticancer activities with the several reported mechanisms including inhibition of angiogenesis, inhibition of tubulin polymerization, and induction of apoptosis etc. OBJECTIVE: This study was focused on to synthesize of 1-(2,4/2,6-difluorophenyl)-3-(2,3/2,4/2,5/3,4- dimethoxyphenyl)-2-propen-1-ones (1-8) and investigate their cytotoxic properties with possible mechanism of action. METHOD: The compounds were synthesized by Claisen-Schmidt condensation. The chemical structures were confirmed by 1H NMR, 13C NMR, DEPT, COSY, HMQC, HMBC, 19F NMR and HRMS. In vitro cytotoxic effects of the compounds against human tumour cell lines [gingival carcinoma (Ca9-22), oral squamous cell carcinoma (HSC-2)] and human normal oral cells [gingival fibroblasts (HGF), periodontal ligament fibroblasts (HPLF)] were evaluated via MTT test. RESULTS: All compounds had higher cytotoxicity than reference compound 5-Fluorouracil (5-FU). The compounds 3-7 had higher potency selectivity expression values (PSE) than 5-FU and PSE values of the compounds were over 100. All chalcone derivatives seem good candidates for further studies according to very remarkable and high PSE values. CONCLUSION: It was clearly demonstrated that compound 7 can induce early apoptosis at a concentration of 10 µM and dose-dependent late apoptosis starting at 10 µM. Compound 7 induced cleavage of the apoptosis marker PARP. The results indicate that new chalcones reported here can promote apoptosis in human tumour cell lines.

Endogenous erythropoietin level and effects of exogenous erythropoietin in a rat model of blunt chest trauma-induced pulmonary contusion.

BACKGROUND: The present objective was to investigate endogen erythropoietin (EPO) level and relationship to oxidative stress within the first 24 hours of blunt chest trauma-induced pulmo-nary contusion (PCn) in a rat model. METHODS: Thirty-five rats were divided into 3 groups. In the baseline control group (BC, n=7), rats were uninjured and untreated. In the positive control group (PC, n=21) rats were injured but untreated. In the EPO-24 group (n=7), rats were injured and a single dose of intra-peritoneal EPO (5000 IU/kg) was administered immediately after lung injury. The PC group was divided into 3 subgroups: PC-6 (n=7), PC-12 (n=7), and PC-24 (n=7). The BC group was subjected to thoracotomy, and the right lung was harvested. The PC subgroups were eu-thanized at 6, 12, and 24 hours after injury, respectively. The EPO-24 group was euthanized at the 24th hour after injury. Lung samples were obtained, levels of malondialdehyde (MDA) and EPO were analyzed, and activities of superoxide dismutase (SOD) and catalase (CAT) were then measured in homogenized lung tissue samples. Histologic damage to lung tissue in the BC group, the EPO-24 group, and PC subgroup euthanized at the 24th hour after injury were scored by a single pathologist blinded to group assignation. RESULTS: Mean MDA levels, as well as SOD and CAT activities, of the BC and EPO-24 groups were significantly lower than those of the PC group (p<0.005). Mean EPO concentra-tion of the PC group was significantly higher than that of the BC group (p<0.005). Lung tis-sue damage scores measured at 24 hours after injury were significantly lower in the EPO-24 group than in the PC group (p<0.005). CONCLUSION: In the present PCn rat model, EPO concentrations, as well as SOD and CAT levels, were high in lung tissue, when measured at 24 hours after PCn. When administered early after chest trauma, EPO significantly attenuated oxidative damage and tissue damage in the early phase, as assessed by biochemical markers and histologic scoring.