BPR1K653, a Novel Aurora Kinase Inhibitor, Exhibits Potent Anti-Proliferative Activity in MDR1 (P-gp170)-Mediated Multidrug-Resistant Cancer Cells

Over-expression of Aurora kinases promotes the tumorigenesis of cells. The aim of this study was to determine the preclinical profile of a novel pan-Aurora kinase inhibitor, BPR1K653, as a candidate for anti-cancer therapy. Since expression of the drug efflux pump, MDR1, reduces the effectiveness of various chemotherapeutic compounds in human cancers, this study also aimed to determine whether the potency of BPR1K653 could be affected by the expression of MDR1 in cancer cells.BPR1K653 specifically inhibited the activity of Aurora-A and Aurora-B kinase at low nano-molar concentrations in vitro. Anti-proliferative activity of BPR1K653 was evaluated in various human cancer cell lines. Results of the clonogenic assay showed that BPR1K653 was potent in targeting a variety of cancer cell lines regardless of the tissue origin, p53 status, or expression of MDR1. At the cellular level, BPR1K653 induced endo-replication and subsequent apoptosis in both MDR1-negative and MDR1-positive cancer cells. Importantly, it showed potent activity against the growth of xenograft tumors of the human cervical carcinoma KB and KB-derived MDR1-positive KB-VIN10 cells in nude mice. Finally, BPR1K653 also exhibited favorable pharmacokinetic properties in rats.BPR1K653 is a novel potent anti-cancer compound, and its potency is not affected by the expression of the multiple drug resistant protein, MDR1, in cancer cells. Therefore, BPR1K653 is a promising anti-cancer compound that has potential for the management of various malignancies, particularly for patients with MDR1-related drug resistance after prolonged chemotherapeutic treatments

Relationship between dichromate oxidizable and total soil organic carbon and distribution of different pools of organic carbon in Vertisols of Central India

Geo-referenced soil samples (0-15 cm) were collected from the farmers fields of Sehore (n = 120) and Vidisha (n = 156) district representing AESR 10.1 to establish the relationship between oxidizable SOC and total SOC in Vertisols of Central India and also to study the distribution of different pools of SOC as well as their relationship with crop yield. Total SOC was apportioned into different pools by using 5, 10 and 20 ml of concentrated H2SO4 that resulted in 3 acid-aqueous solution ratio of 0.5:1, 1:1 and 2:1. Also crop yields during the following winter season and rainy season from the geo-reference fields were recorded and were transformed to % relative yield. Oxidizable SOC (y) was related to total SOC (x) in the form of y = 0.825x – 0.086 (R2 = 0.958, n = 276), indicating that oxidizable SOC comprised 82.5% of the total SOC. Therefore it was recommended that a correction factor of 1.21 should be used to convert oxidizable SOC values to get the estimate of total SOC. The mean crop productivity was better related to oxidizable SOC (r = 0.5275) as compared to total SOC(r = 0.4886). The threshold and optimum values of oxidizable SOC were 3.2 and 11.2 g C/kg, respectively, whereas the threshold and optimum values for total SOC were 3.87 and 14.1 g C/kg, respectively. Among the different pools, less labile C was highly correlated (r = 0.5871) with the crop productivity, the computed threshold and optimum value for less labile C were 1.53 and 5.2 g C/kg, respectively

Identification of Potent EGFR Inhibitors from TCM Database@Taiwan

Overexpression of epidermal growth factor receptor (EGFR) has been associated with cancer. Targeted inhibition of the EGFR pathway has been shown to limit proliferation of cancerous cells. Hence, we employed Traditional Chinese Medicine Database (TCM Database@Taiwan) (http://tcm.cmu.edu.tw) to identify potential EGFR inhibitor. Multiple Linear Regression (MLR), Support Vector Machine (SVM), Comparative Molecular Field Analysis (CoMFA), and Comparative Molecular Similarities Indices Analysis (CoMSIA) models were generated using a training set of EGFR ligands of known inhibitory activities. The top four TCM candidates based on DockScore were 2-O-caffeoyl tartaric acid, Emitine, Rosmaricine, and 2-O-feruloyl tartaric acid, and all had higher binding affinities than the control Iressa®. The TCM candidates had interactions with Asp855, Lys716, and Lys728, all which are residues of the protein kinase binding site. Validated MLR (r² = 0.7858) and SVM (r² = 0.8754) models predicted good bioactivity for the TCM candidates. In addition, the TCM candidates contoured well to the 3D-Quantitative Structure-Activity Relationship (3D-QSAR) map derived from the CoMFA (q² = 0.721, r² = 0.986) and CoMSIA (q² = 0.662, r² = 0.988) models. The steric field, hydrophobic field, and H-bond of the 3D-QSAR map were well matched by each TCM candidate. Molecular docking indicated that all TCM candidates formed H-bonds within the EGFR protein kinase domain. Based on the different structures, H-bonds were formed at either Asp855 or Lys716/Lys728. The compounds remained stable throughout molecular dynamics (MD) simulation. Based on the results of this study, 2-O-caffeoyl tartaric acid, Emitine, Rosmaricine, and 2-O-feruloyl tartaric acid are suggested to be potential EGFR inhibitors.National Science Council of Taiwan (NSC 99-2221-E-039-013-)Committee on Chinese Medicine and Pharmacy (CCMP100-RD-030)China Medical University (CMU98-TCM)China Medical University (CMU99-TCM)China Medical University (CMU99-S-02)China Medical University (CMU99-ASIA-25)China Medical University (CMU99-ASIA-26)China Medical University (CMU99-ASIA-27)China Medical University (CMU99-ASIA-28)Asia UniversityTaiwan Department of Health. Clinical Trial and Research Center of Excellence (DOH100-TD-B-111-004)Taiwan Department of Health. Cancer Research Center of Excellence (DOH100-TD-C-111-005

Not Available

Not AvailableThe present study compares the distribution and nature of heavy metals in composts from 12 cities of India, prepared from different types of processed urban solid wastes, namely mixed wastes (MWC), partially segregated wastes (PSWC), and segregated bio-wastes (BWC). Compost samples were physically fractionated by wet sieving, followed by extraction of heavy metals by dilute HCl and NaOH. Bigger particles (>0.5 mm) constituted the major fraction in all three types of composts and had a relatively lower concentration of organic matter and heavy metals, the effect being more pronounced in MWC and PSWC in which a significant portion of the heavy metals was distributed in finer size fractions. Cd, Ni, Pb, and Zn were extracted to a greater extent by acid than by alkali, the difference being greater in MWC, which contained a higher amount of mineral matter. In contrast, Cu and Cr were extracted to a greater extent by dilute alkali, particularly from BWC containing a higher amount of organic matter. Water-soluble heavy metals were generally related to the water-soluble C or total C content as well as to pH, rather than to their total contents. This study concludes that wet sieving with dilute acid can effectively reduce heavy metal load in MWC and PSWC.Not Availabl

Not Available

Not AvailableRavine formed from intricate network of gullies because of localized physical degradation due to surface runoff affecting the friable unconsolidated material in the formation of perceptible channels resulting in undulating terrain with fragile ecosystem. Over-exploitation of this vast tract of existing ravine lands coupled with improper management practices has led to deterioration of soil health and poses threat to adjoining productive agricultural lands. Under ravine landscapes, soil undergoes various changes due to accelerated erosional processes. With rapidly shrinking per capita availability of land, there is a growing need for restoration of these areas for productive land uses. Maintenance of soil organic carbon is one of the most important factors for aggregate stability, soil structural durability and nutrient availability in ravine areas. Deficiency of nutrients and poor water retention are two major causative factors of stagnation in crop productivity in ravine lands. In this chapter, an attempt has been made to consolidate various best nutrient management practices for soils under ravine region for increasing crop productivity and improving soil health. Also, there is a need to harness and manage the indigenous technical knowledge and fine-tune them to suit the modern needs. Overall, the twin aspect of devising strategies for leveraging resources to tackle the challenge of enhancing soil health and carbon sequestration will help in combating climate change without compromising economic development in ravine areas. The future R&D strategies for maintaining soil health, crop productivity and environmental sustainability in degraded ravine land have also been includedNot Availabl

Not Available

Not AvailableAn incubation study was conducted to characterize soil quality as affected by organic amendments (FYM, biochar and, poultry manure @ 25 t ha-1) along with or without fly ash (@ 22.4 t ha-1) in Vertisol. Physical and chemical parameters of soil quality like pH, EC, bulk density, porosity, moisture content, organic carbon and available N, P, K measured at the end of incubation period i.e. 10th week showed that combined application of soil amendments (FYM + fly ash, biochar + fly ash, poultry manure + fly ash) had significantly better results than individual application of the respective soil amendments. Soil microbial biomass carbon (SMBC) and dehydrogenase enzyme activity (DHA) increased steadily up to 6th weeks of incubation with a marginal decrease during last phase. At the end of incubation period (10th week), SMBC and DHA was highest in the soil amended with FYM + fly ash; T5 (476.6 mg/kg of soil and 10.28 µg TPF g-1 soil h-1). The soils treated with organic amendments particularly FYM and poultry manure along with fly ash showed best performance in terms of soil quality improvement in Vertisol.Not Availabl

Synthesis of 4-(benzamide)- and 4-(phthalimide)-substituted phenoxypropanolamines and their beta1, beta2-adrenergic receptors binding studies

N-[4-(2-Hydroxy-3-isopropylaminopropoxy)phenyl-l-oxo-isoindoline 3 possess a cardioselective beta-adrenergic receptor binding affinity. Herein we attempted to synthesize the unreduced compound N-[4-(2-hydroxy-3-isopropylaminopropoxy)phenyl]phthalimide 4. But, reaction of N-[4-(2,3-epoxypropoxy)phenyl]plithalimide 10 with isopropylamine opened the phthalimide ring to give N-[4-(2-hydroxy-3-isopropylaminopeopoxy)phenyll-2-isopropylcarbamoylbenzainide 12 instead of 4 as expected. While treatment of 10 with tert-buitylamine gives N-[4-(3-tert-butylamino-2-hydroxypropoxy)phenyllphthalimide 15. Further, reaction of 15 with isopropylamine opened the phtlialimide ring to yield N-[4-(3-tertbutylamino-2-hydroxypropoxy)phenyl]-2-isopropylearbainoylbenzamide 16. Also, reaction of N-[4-(2,3-epoxypropoxy)phenyl]-5,6-dimethoxyphthalimide 11 with isopropylamine affords the phthalimide ring opened analogue N-[4-(2-hydroxy3-isopropylaminopropoxy)phenyl]-2-isopropylcarbamoyl-5,6-dimethoxybeiizamide 13. Compounds 12, 13, 15 and 16 have been tested for their in vitro beta(1)- and beta(2)-adrenergic receptor binding affinity using turkey erythrocyte-membrane (01) and lung homogenate of rats (beta(2)). The percentage inhibition of [H-3]DHA binding to both beta(1)-and beta(2)-adrenergic receptors are compared with that of the standard non-selective beta-adrenergic blocking agent propranolol 1 and selective agent atenolol. All the tested compounds exhibit binding affinity to PI-adrenergic receptors at the tested concentration [10(-5) M] and most of them (12, 15, 16) exhibit cardioselectivity (selectivity ratio > 1). The dimethoxy analogue 13 shows selectivity towards beta(2)-adrenergic receptor (selectivity ratio < 1)

Not Available

Not AvailableToday India is not only self-sufficient in respect of demand for food but also a net exporter of agri-products occupying 7th position globally. It is one of the top producers of cereals (wheat and rice), pulses, fruits, vegetables, milk, meat and marine fish. India now ranks 2nd world wide in farm output and is the world’s largest producer of fresh fruits and vegetables, milk, major spices, various crops such as jute, staples such as millets and castor oil seed. It is also the second largest producer of wheat and rice (Dhawan 2017). Agriculture and allied sectors like forestry and fisheries accounted 13.7% of the GDP (Gross Domestic Production) in 2013 but employed 50% of the workforce. The Green Revolution during the sixties not only led to food self-sufficiency for the country but also helped to reduce the poverty and hunger. Despite five-fold increase in food grains production, as against a four-fold increase in population, India still have around 250 million people who live in poverty and about 45 million children below five years of age who are malnourished. Moreover, after 50 years of Green Revolution, the country is also facing the second-generation challenges like decline in the factor productivity, poor soil health, loss of soil organic carbon (SOC), ground and surface water pollution, water related stress, increased incidence of pests and diseases, increased cost of inputs, decline in farm profits and the adverse impact of climate change (Paroda 2018). In many parts of the country, decline in soil fertility/health is due to removal or burning of crop residues, reduced manuring, intensive cropping, imbalanced and excessive applications of fertilizers and …Not Availabl