A comprehensive review on ethnomedicinal, phytochemical and pharmacological properties of genus Bistorta (L.) scop.

The genus Bistorta comprises about 43 accepted species that are widely used by local people and medicinal practitioners for the treatment of rheumatism, tuberculosis, inflammation, respiratory infection, and other diseases. The objective of this review is to present up-to-date information from the scientific literature about the phytochemistry, pharmacology, and toxicology of Bistorta. At present, there is a lack of a comprehensive review that consolidates the various scientific studies conducted on the genus Bistorta. To address this knowledge gap, a global review has been compiled on the genus Bistorta, which emphasizes ethnomedicinal uses, phytochemistry, and pharmacology. To gather information about Bistorta, relevant keywords were used to search internet databases including Google scholar, PubMed, ResearchGate, Web of Science, Europe PMC, CNKI, and Wiley Online Library. Additionally, published books that provided an overview of existing literature studies were consulted for reference purposes. Chemical structures and formulas of compounds were verified using the PubChem database and drawn using Chem Draw Ultra 6.0. The scientific nomenclature utilized in this review follows The World Flora Online and The Plant of the World Online (PoWo). A comprehensive evaluation of literature sources revealed that the genus Bistorta has been recognized for its ethnomedical properties and has been used in traditional healthcare for several millennia. Chemical analysis has identified various compounds such as phenolics, flavonoids saponins, terpenes, sterols, and coumarins which have been shown to have significant pharmacological effects such as anti-tumor, anti-inflammatory, anti-oxidant anti-rheumatic and anti-microbial properties. The pharmacological research has only partially validated the traditional and local uses of Bistorta species. Further research is required to investigate the mechanisms of the plant's active compounds, as well as its potential therapeutic applications in treating conditions like diabetes and neurodegenerative diseases. Additionally, there is no clinical evidence to provide the health benefits of these plants. To confirm the pharmacological activities, clinical efficacy, and non-toxicity of Bistorta species, more comprehensive and systematic preclinical studies, and clinical trials are needed.

6-Aryl-4-cycloamino-1,3,5-triazine-2-amines: synthesis, antileukemic activity, and 3D-QSAR modelling.

Despite significant progress in immunotherapy and chimeric antigen receptor T cell therapy of leukemia, chemotherapy is the major treatment option for the disease. Therefore, the development of potent and safe drugs for standard and targeted chemotherapy of leukemia remains an important task for medicinal chemists. A library of 94 diverse 6-aryl-4-cycloamino-1,3,5-triazine-2-amines was prepared using a one-pot microwave-assisted protocol, which involves a three-component reaction of cyanoguanidine, aromatic aldehydes and cyclic amines, and subsequent dehydrogenative aromatization of the dihydrotriazine intermediates in the presence of alkali. The cytotoxic properties of prepared compounds were evaluated against the leukemic Jurkat T cell line and the selectivity of the 24 most active compounds was also assessed using a normal fibroblast MRC-5 cell line, indicating selective antiproliferative activity against leukemic cells. The structure-activity relationship was analysed, and the prepared 3D-QSAR model was found to predict the antileukemic activity of the compounds with reasonable accuracy. In the cell morphology study, both apoptosis and necrosis features were observed in Jurkat T cells after treatment with the most active compound.

Advanced detection of coronary artery disease via deep learning analysis of plasma cytokine data.

The 2017 World Health Organization Fact Sheet highlights that coronary artery disease is the leading cause of death globally, responsible for approximately 30% of all deaths. In this context, machine learning (ML) technology is crucial in identifying coronary artery disease, thereby saving lives. ML algorithms can potentially analyze complex patterns and correlations within medical data, enabling early detection and accurate diagnosis of CAD. By leveraging ML technology, healthcare professionals can make informed decisions and implement timely interventions, ultimately leading to improved outcomes and potentially reducing the mortality rate associated with coronary artery disease. Machine learning algorithms create non-invasive, quick, accurate, and economical diagnoses. As a result, machine learning algorithms can be employed to supplement existing approaches or as a forerunner to them. This study shows how to use the CNN classifier and RNN based on the LSTM classifier in deep learning to attain targeted "risk" CAD categorization utilizing an evolving set of 450 cytokine biomarkers that could be used as suggestive solid predictive variables for treatment. The two used classifiers are based on these "45" different cytokine prediction characteristics. The best Area Under the Receiver Operating Characteristic curve (AUROC) score achieved is (0.98) for a confidence interval (CI) of 95; the classifier RNN-LSTM used "450" cytokine biomarkers had a great (AUROC) score of 0.99 with a confidence interval of 0.95 the percentage 95, the CNN model containing cytokines received the second best AUROC score (0.92). The RNN-LSTM classifier considerably beats the CNN classifier regarding AUROC scores, as evidenced by a p-value smaller than 7.48 obtained via an independent t-test. As large-scale initiatives to achieve early, rapid, reliable, inexpensive, and accessible individual identification of CAD risk gain traction, robust machine learning algorithms can now augment older methods such as angiography. Incorporating 65 new sensitive cytokine biomarkers can increase early detection even more. Investigating the novel involvement of cytokines in CAD could lead to better risk detection, disease mechanism discovery, and new therapy options.

Exploring morphological variability, in vitro antioxidant potential, and HR-LCMS phytochemical profiling of Phlomis cashmeriana Royle ex Benth. across different habitats of Kashmir Himalaya.

Phytochemicals are broadly acknowledged for their health-promoting effects owing to the fact of their capacity to counteract free radicals (e.g., superoxide anion radical, hydroxyl radical, hydroperoxyl radical, singlet oxygen, hypochlorite, and nitric oxide) and shield against oxidative stress induced by environmental factors. This study aimed to investigate the relationship between altitude, morphology, soil parameters, in vitro antioxidant potential and phytochemical composition of Phlomis cashmeriana collected from four different locations of Kashmir Himalaya characterized by diverse habitats and elevations. Various factors, such as extraction method, solvent polarity, and habitat conditions, can impact the quantity and efficacy of phytochemicals in plants. The aim of current study was to analyze phytochemical composition and antioxidant activity of P. cashmeriana, an important medicinal plant found in the Kashmir Himalaya region. The antioxidant activity was accessed using several assays and the plant populations were selected based on their diverse habitat features and altitudes. HR-LCMS was conducted for both below-ground and above-ground parts. Some important compounds such as, catechin, vinainsenoside, acutilobin, and kaempferol were reported for the first time from P. cashmeriana. Results showed that methanol was the most efficient solvent for extracting phytochemicals. During the current study, it was also found that the below-ground parts exhibited superior antioxidant activity compared to the above-ground parts. Notably, Site IV demonstrated the highest antioxidant potential; a positive correlation between altitude and antioxidant activity was also found. In conclusion, present research identified specific elite populations having highest antioxidant potential and are well-suited for large-scale cultivation of P. cashmeriana.

Incidence of formation of anti-D between patients with and without a history of solid organ transplant.

BACKGROUND AND OBJECTIVES: Solid organ transplant surgeries including liver transplants constitute a substantial risk of bleeding complications and given frequent national blood shortages, supporting D-negative transplant recipients with D-negative red blood cell products perioperatively can be difficult for the transfusion services. This study was designed to compare the incidence of alloimmunization after D-mismatched red cell transfusions between patients with and without a history of solid organ transplant at a single tertiary care hospital. The patients undergoing solid organ transplants are on strong immunosuppressive regimens perioperatively to help reduce the risk of rejection. We hypothesized that the use of these immunosuppressive agents makes these patients very less likely to mount an immune response and form anti-D antibodies when exposed to the D-positive red blood cell products perioperatively. STUDY DESIGN AND METHODS: At our center, D-negative patients who received ≥1 unit of D-positive red blood cell products were identified using historical transfusion records. Antibody testing results were examined to determine the incidence of the formation of anti-D and any other red cell alloantibodies after transfusion and these results were compared between patients with and without a history of solid organ transplant. RESULTS: We were able to identify a total of 22 patients over 10 years with D-negative phenotype who had undergone a solid organ transplant and had received D-positive red blood cell products during the transplant surgeries. We also identified a second group of 54 patients with D-negative phenotype who had received D-positive red blood cell products for other indications including medical and surgical. A comparison of the data showed no new anti-D formation among patients with a history of D mismatched transfusion during solid organ transplant surgeries. CONCLUSION: Among our limited study population, we observed a very low likelihood of D alloimmunization among solid organ transplant recipients. A larger, prospective study could help further evaluate the need for prophylactic D matching for red cell transfusions during solid organ transplant surgeries.

Successful Use of Bortezomib in an Adolescent with Refractory TTP.

With increasing early and upfront use of rituximab and caplacizumab in the modern management of immune-mediated thrombotic thrombocytopenic purpura (iTTP), the risk of refractory disease is expected to decline. However, despite the use of adequate initial therapy, a small subset of patients develop a refractory disease which is difficult to manage. Bortezomib has come to be known as a safe and effective treatment option for refractory iTTP, but its use in children is limited. Here, we describe the case of an adolescent patient with refractory iTTP who had a satisfactory and sustained response to the use of bortezomib.

Exploring variations in gait patterns and joint motion characteristics in school-aged children across different walking speeds: a comprehensive motion analysis study.

This study aimed to investigate differences in gait patterns among individuals with different walking speeds and identify the range of motion (ROM) and angular velocity for various joints during gait. Forty-five schoolchildren were randomly selected for this study. To capture their walking patterns, two FDR-AX700 4K HDR camcorders were positioned to observe the predetermined walkway. Each participant completed a 5-meter walk at various speeds, including slow, normal, and fast, while maintaining a straight stride. There were significantly higher ROM and angular velocity (p<0.05) at the hip, knee, and ankle joints across most stages of walking at a faster speed compared to slow and normal speeds. At the same time, the angular velocity was significantly higher at the hip joint during hip extension terminal stance at normal speed compared to slow and fast speeds (p<0.05, ƞ2 =0.74). Similarly, the ROM of knee flexion swing, ankle plantar flexion loading response, and ankle dorsiflexion midswing angular velocity were significantly higher during normal walking speed (p<0.05). Conversely, slow-speed walking showed significantly higher ROM at knee extension terminal swing (ƞ2=0.52) and ankle dorsiflexion terminal stance (ƞ2=0.78) (p<0.05). The results indicate that individuals with different walking speeds exhibit significant differences in gait patterns. Slower walking speeds resulted in lower gait velocity and different joint motions compared to faster walking speeds.

Effects of an aerobic training program on liver functions in male athletes: a randomized controlled trial.

The optimal functioning of the liver is essential for athletic performance. It is necessary to maintain the liver's enzymes at an optimal level so that liver cells can be protected from inflammation or damage. This study investigated the effects of a 12-week aerobic exercise program on the liver function of adult athletes. A pretest-posttest experimental design was used. A total of thirty healthy male athletes (football players) aged 21 to 24 years were recruited for this study and randomly and equally divided into the experimental group (EG) and control group (CG). The CG did not participate in any special activities. The EG performed an aerobic training program consisting of several exercises for 12 weeks. Evaluation of all participants in both groups was carried out before and after the intervention by measuring the blood levels of Alkaline phosphate, AST/SGOT, ALT/SGPT, Bilirubin Total/indirect/direct, Albumin, Globulin, and Total protein using the standard methods by collecting blood samples. There was a significant decrease (p < 0.05) in Bilirubin and globulin levels in the EG after 12 weeks of aerobic training sessions. However, there was no significant difference in alkaline phosphate, AST/SGOT, ALT/SGPT Total protein, and Albumin (p > 0.05) between both groups post-treatment. The 12 weeks of aerobic training used in the study can potentially improve the liver function of adult athletes.

Recent developments in space food for exploration missions: A review.

Food and nutrition have greatly influenced the effectiveness of space exploration missions. With the development of technology, attention is now being paid more and more to preparing food for the microgravity environment, taking into account factors like nutrient density, shelf life, optimized packaging, preservations, innovations, challenges, and applications. The spectrum of food products is designed to meet the balanced nutritional requirements, reduce hazards encountered by astronauts, and utilize space in explorers during space missions. For the long duration of space missions and, consequently, for human permanence in space, it is crucial to provide humans with an adequate supply of fresh food to meet their nutritional needs. By doing this, astronauts could reduce the health risks associated with psychological stress, microgravity, and radiation exposure from space. Maintaining astronauts' health, happiness, and vitality during long-duration human-crewed missions has recently emerged as an essential and critical research area. The food they eat appears to be an important factor. For short-term space missions, astronauts' food could be brought from earth. Still, for long-term space missions to the Moon, Mars, and other distant missions, which are the current research destinations, they must find a way to eat, such as by cultivating plants or finding other means of survival. Scientists and researchers are attempting to develop novel food production technologies or systems that require minimal inputs while maximizing safe, nutritionally balanced, and delicious food outputs for long-duration space missions that could benefit people on earth. This review summarizes various aspects of space food, including evolution, innovations, technological advancements to prolong shelf life, and astronauts' problems. It also involves current research, including space foods like 3D printing and space farming for a long-term space mission.

Habitat suitability, range dynamics, and threat assessment of Swertia petiolata D. Don: a Himalayan endemic medicinally important plant under climate change.

In the current era of the anthropocene, climate change is one of the main determinants of species redistribution and biodiversity loss. Worryingly, the situation is alarming for endemic and medicinally important plant species with a narrow distributional range. Therefore, it is pivotal to inspect the influence of accelerated climate change on medicinally important threatened and endemic plant species. Using an ensemble approach, the current study aims at modelling the present distribution and predicting the future potential distribution coupled with the threat assessment of Swertia petiolata-a medicinally important endemic plant species in the Himalayan biodiversity hotspot. Our study revealed that under current climatic scenarios, the suitable habitats for the species occur across the western Himalayan region which includes the north-western Indian states (Jammu and Kashmir, Himachal Pradesh, and southern Uttarakhand), northern Pakistan, and north-western Nepal. Also, temperature seasonality (BIO4) and precipitation seasonality (BIO15) are the most significant bioclimatic variables determining the distribution of S. petiolata. Furthermore, the study projected a reduction in the suitable habitats for the species under future changing climatic scenarios with a reduction ranging from - 40.298% under RCP4.5 2050 to - 83.421% under RCP8.5 2070. Most of the habitat reduction will occur in the western Himalayan region. In contrast, some of the currently unsuitable Himalayan regions like northern Uttarakhand will show increasing suitability under climate change scenarios. The current study also revealed that S. petiolata is classified as Near Threatened (NT) following the IUCN criterion B. Hopefully, the present study will provide a robust tool for predicting the cultivation hotspots and devising scientifically effective conservation strategies for this medicinally important plant species in the Himalaya and similar environments elsewhere in the world.

Synthesis and Characterization of the Nanogold-Bound Ternary Copper(II) Complex of Phenanthroline and Cysteine as Potential Anticancer Agents.

The aim of this study was to synthesize and characterize a nanogold-{[(Cu)(phen)(cys)(H2O)]NO3}n conjugate and to evaluate its antiproliferative property against the breast cancer cell line (MCF7) and normal cell line (MCF10A). Nanogold solution was prepared using the Turkevich method. In one approach, a ternary copper(II) complex of 1,10-phenanthroline with l-cysteine, [(Cu)(phen)(cys)(H2O)]NO3, was first prepared and then tethered with the gold nanoparticles. In another approach, gold nanoparticles were reacted with l-cysteine, copper(II) nitrate, and 1,10-phenanthroline subsequently. The synthesized [(Cu)(phen)(cys)(H2O)]NO3 complex was characterized by Fourier transform infrared (FTIR) and electrospray ionization mass spectrometry techniques, which showed that l-cysteine was bound to the copper through carboxylic and amino groups, with the thiol moiety remaining free. The free thiol group was bound to the nanogold surface to form the nanogold-{[(Cu)(phen)(cys)(H2O)]NO3}n conjugate, as evidenced by the increase in the surface plasmon absorption band in ultraviolet-visible and the absence of a thiol peak in FTIR of the nanogold-copper complex conjugate. The anticancer activity of the nanogold-copper complex conjugate and the free copper complex against a breast cancer cell line (MCF7) and their toxicity on a normal cell line (MCF10A) were examined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Results suggested that the nanogold-{[(Cu)(phen)(cys)(H2O)]NO3}n conjugate demonstrates a selective antiproliferative and proapoptotic effect on the breast cancer cells, confirming the potential of the nanogold-copper complex conjugate as an anticancer agent.

Study of synergistic effects of Ficus Carica leaves extract mediated chemo-photodynamic therapy on rhabdomyosarcoma cells.

BACKGROUND: Chemotherapy for rhabdomyosarcoma (RD) is effective, but it has critical side effects and unavoidable challenges. Photodynamic therapy (PDT) is an approach to treating cancer with relatively moderate side effects. Plant products are a rich source of polyphenols, which have potent antioxidant and anticancer activities. Therefore, their research has become an emerging field in recent decades. PURPOSE: This work aimed to evaluate the potential of hydrophobic extract of Ficus Carica (FC) to determine whether FC in the presence of low dose chemo and Aluminium Phthalocyanine (Photosense®) mediated photodynamic therapy synergistically enhances the treatment efficacy of RD cells. METHOD: FC with and without combination with individual therapeutic modalities like photosense mediated photodynamic therapy, chemotherapy, and their combinations were studied for cell viability and morphological changes in invitro RD cells. A semiconductor diode laser (630 nm) was used as a light source in PDT. The cytotoxic effect of FC on cell viability and cellular morphological changes were investigated by MTT reagent and a camera attached to an inverted visible light microscope. The effect of FC, followed by di-combination with low dose chemo (doxorubicin-HCl, and dacarbazine), Photosense® mediated PDT and chemo-Photosense® mediated PDT (tri-combination) at 630 nm diode laser and 10 J/cm2 fluency were also investigated by MTT reagent. The combination index method is used to identify the synergistic effect of combination therapy by using CompuSyn software based on the Chou-Talalay method. RESULTS: The dose-dependent effect of FC on cell viability and cellular morphological changes were observed in the RD cell line. It was found that the pre incubation of FC potentiated the anticancer effect as a neoadjuvant agent for doxorubicin-HCl and decarbazine based chemotherapy, Photosense® mediated PDT and chemo-PDT (tri-combination) with synergistic effect (CI<1). CONCLUSION: These results suggest a possible thread that the low dose combination of the aforementioned therapeutic modalities in the presence of FC remarkably enhances the treatment efficacy of RD in comparison with a single-agent treatment modality. The proposed sequence of FC with chemo and PDT might present better therapeutic outcomes in RD therapies and may provide result for RD metastasis. FC may also be used in the application of phyto-PDT to cancer in the future.

Seroprevalence and Risk Factors of SARS CoV-2 in Health Care Workers of Tertiary-Care Hospitals in the Province of Khyber Pakhtunkhwa, Pakistan

BackgroundHigh number of SARS-CoV-2 infected patients has overburdened healthcare delivery system, particularly in low-income countries. In the recent past many studies from the developed countries have been published on the prevalence of SARS CoV-2 antibodies and the risk factors of COVID-19 in healthcare-workers but little is known from developing countries. MethodsThis cross-sectional study was conducted on prevalence of SARS-CoV-2 antibody and risk factors for seropositivity in HCWs in tertiary-care hospitals of Peshawar city, Khyber Pakhtunkhwa province Pakistan. ResultsThe overall seroprevalence of SARS CoV-2 antibodies was 30{middle dot}7% (CI, 27{middle dot}8-33{middle dot}6) in 1011 HCWs. Laboratory technicians had the highest seropositivity (50{middle dot}0%, CI, 31{middle dot}8-68{middle dot}1). Risk analysis revealed that wearing face-mask and observing social-distancing within a family could reduce the risk (OR:0{middle dot}67. p<0{middle dot}05) and (OR:0{middle dot}73. p<0{middle dot}05) while the odds of seropositivity were higher among those attending funeral and visiting local-markets (OR:1{middle dot}83. p<0{middle dot}05) and (OR:1{middle dot}66. p<0{middle dot}01). In Univariable analysis, being a nursing staff and a paramedical staff led to higher risk of seropositivity (OR:1.58. p< 0{middle dot}05), (OR:1{middle dot}79. p< 0{middle dot}05). Fever (OR:2{middle dot}36, CI, 1{middle dot}52- 3{middle dot}68) and loss of smell (OR:2{middle dot}95, CI: 1{middle dot}46-5{middle dot}98) were significantly associated with increased risk of seropositivity (p<0.01). Among the seropositive HCWs, 165 (53{middle dot}2%) had no symptoms at all while 145 (46{middle dot}8%) had one or more symptoms. ConclusionThe high prevalence of SARS-CoV-2 antibodies in HCWs warrants for better training and use of protective measure to reduce their risk. Early detection of asymptomatic HCWs may be of special importance because they are likely to be potential threat to others during the active phase of viremia.

ESTIMATING COVID-19 INFECTIONS IN HOSPITAL WORKERS IN THE UNITED STATES

ObjectiveWe estimated that how many hospital workers in the United States (US) might get infected or die in the COVID-19 pandemic. We also estimated the impact of personal protective equipment (PPE) and age restrictions on these estimates. MethodsOur secondary analyses estimated hospital worker infections in the US based on health worker infection and death rates per 100 deaths from COVID-19 in Hubei and Italy. We used Monte Carlo simulations to compute point estimates with 95% confidence intervals for hospital worker infections in the US based on the two scenarios. We computed potential decrease in infections if the PPE were available only to those involved in direct care of COVID-19 patients ([~] 30%) and if workers aged [≥] 60 years are restricted from patient care. Estimates were adjusted for hospital workers per bed in the US compared to China and Italy. ResultsThe hospital worker infections per 100 deaths were 108.2 in Hubei and 94.1 in Italy. Based on Hubei scenario, we estimated that about 53,640 US hospital workers (95% CI: 43,160 to 62,251) might get infected from COVID-19. The Italian scenario suggested 53,097 US hospital worker (95% CI: 37,133 to 69,003) might get infected during the pandemic. Availability of PPE to high-risk workers could reduce counts to 28,100 (95% CI: 23,048 to 33,242) considering Hubei and to 28,354 (95% CI: 19,829 to 36,848) considering Italy. Restricting hospital workers aged [≥] 60 years from direct patient care reduced counts to 1,985 (95% CI: 1,627 to 2,347) considering Hubei and to 2,002 (95% CI: 1,400 to 2,602) considering the Italian scenario. ConclusionWe estimated significant burden of illness due to COVID-19 if no strategies are adopted. Making PPE available to all hospital workers and reducing exposure of hospital workers above the age of 60 could have significant reductions in hospital worker infections. VISUAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/20055988v1_fig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@1a107c7org.highwire.dtl.DTLVardef@105ad1dorg.highwire.dtl.DTLVardef@1a883dcorg.highwire.dtl.DTLVardef@69108d_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO Estimated number of COVID-19 related infections among healthcare workers in the United States based on Hubei and Italian scenarios C_FIG

6,N 2-Diaryl-1,3,5-triazine-2,4-diamines: synthesis, antiproliferative activity and 3D-QSAR modeling.

A library of 126 compounds with a 6,N 2-diaryl-1,3,5-triazine-2,4-diamine scaffold was prepared using a one-pot, microwave-assisted method from readily available cyanoguanidine, aromatic aldehydes and arylamines. The three-component condensation of these reagents in the presence of hydrochloric acid was followed by the treatment with a base, which promoted a rearrangement of the dihydrotriazine ring and its dehydrogenative aromatization. The antiproliferative properties of the prepared compounds were evaluated using three breast cancer cell lines. The most promising results were obtained in the growth inhibition of the triple negative MDA-MB231 breast cancer cells. The active compounds were also selective against cancer cells and did not affect growth of the non-cancerous MCF-10A breast cell line. Analyzing the structure-activity relationship within the series, we built a 3D-QSAR model for the further design of more potent anticancer compounds.

Design, synthesis, and biological evaluation of new 6,N 2-diaryl-1,3,5-triazine-2,4-diamines as anticancer agents selectively targeting triple negative breast cancer cells.

New 6,N 2-diaryl-1,3,5-triazine-2,4-diamines were designed using the 3D-QSAR model developed earlier. These compounds were prepared and their antiproliferative activity was evaluated against three breast cancer cell lines (MDA-MB231, SKBR-3 and MCF-7) and non-cancerous MCF-10A epithelial breast cells. The synthesized compounds demonstrated selective antiproliferative activity against triple negative MDA-MB231 breast cancer cells. The most active compound in the series inhibited MDA-MB231 breast cancer cell growth with a GI50 value of 1 nM. None of the tested compounds significantly affected the growth of the normal breast cells. The time-dependent cytotoxic effect, observed when cytotoxicity was assessed at different time intervals after the treatment, and morphological features, observed in the fluorescence microscopy and live cell imaging experiments, suggested apoptosis as the main pathway for the antiproliferative activity of these compounds against MDA-MB231 cells.

Whispering gallery mode lasing in mesomorphic liquid crystal microdroplets.

In recent years, investigation on the non-display applications of liquid crystals has increased considerably. One of the emerging applications is whispering gallery mode (WGM) lasing. Here, we report experimental studies on the morphology and WGM lasing in nematic (N), smectic-A (SmA) and smectic-C (SmC) microdroplets dispersed in a highly transparent and low refractive index perfluopolymer. The mesomorphic microdroplets, obtained by varying the temperature, exhibit radial director configuration. The SmA microdroplets are found to be highly stable and robust against mechanical stress compared to the N and SmC microdroplets. We study lasing properties such as intensity, threshold pump energy and linewidth, and show that overall the SmA microdroplets are superior to the N and SmC microdroplets. The experimental results are discussed based on the orientation of the dye molecules, director fluctuations and tilting at the interface.

New One-Pot Synthesis of 1,3,5-Triazines: Three-Component Condensation, Dimroth Rearrangement, and Dehydrogenative Aromatization.

A new, effective one-pot synthesis of the 6, N2-diaryl-1,3,5-triazine-2,4-diamines under microwave irradiation was developed. The method involved an initial three-component condensation of cyanoguanidine, aromatic aldehydes, and arylamines in the presence of hydrochloric acid. Without isolation, the resulting 1,6-diaryl-1,6-dihydro-1,3,5-triazine-2,4-diamines were treated with a base to initiate Dimroth rearrangement and spontaneous dehydrogenative aromatization, affording the desired compounds. The developed method was found to be sufficiently general in scope, tolerating various aromatic aldehydes and amines; by using their combinations in the first step, a representative library of 110 compounds was successfully prepared and screened for anticancer properties.

Fused Heterocyclic Systems with an s-Triazine Ring. 34. Development of a Practical Approach for the Synthesis of 5-Aza-isoguanines.

Purine isosteres present excellent opportunities in drug design and development. Using isosteres of natural purines as scaffolds for the construction of new therapeutic agents has been a valid strategy of medicinal chemistry. Inspired by the similarity to isoguanine, we attempted to develop a practical method for the preparation of 5-aza-isoguanines. Several synthetic approaches were explored to establish a robust general protocol for the preparation of these compounds. The significant difference in the reactivity of the C-5 and C-7 electrophilic centers of 1,2,4-triazolo[1,5-a][1,3,5]triazines (5-azapurines) towards nucleophiles was demonstrated. The most practical and general method for the preparation of 5-aza-isoguanines involved a regioselective reaction of ethoxycarbonyl isothiocyanate with a 5-aminotriazole. The intramolecular ring closure of the resulted product followed by the S-methylation afforded 7-methylthio-2-phenyl-1,2,4-triazolo[1,5-a][1,3,5]triazin-5-one, which could be effectively aminated with various amines. The resulted 5-aza-isoguanines resemble a known purine nucleoside phosphorylase inhibitor and could be interesting for further investigations as potential anticancer agents.