Radiolabeling and preclinical animal model evaluation of DTPA coupled 99mTc-labelled flutamide complex ([99mTc]DTPA-FLUT) as a potential radiotracer for cancer imaging.

BACKGROUND: Advances in molecular imaging strategies have had an effect on precise diagnosis and treatment. Research has been intensified to develop more effective and versatile radiopharmaceuticals to uplift diagnostic efficiency and, consequently, the treatment. PURPOSE: To label the flutamide (FLUT) coupled with diethylenetriamine pentaacetate (DTPA) with technetium-99 m (99mTc) and to evaluate its binding efficiency with rhabdomyosarcoma (RMS) cancer cells. MATERIAL AND METHODS: Radiolabeling of FLUT with 185 MBq freshly eluted 99mTcO4-1 was carried out via DTPA bifunctional chelating agent using stannous chloride reducing agent at pH 5. The labeled compound was assessed for its purity using chromatography analysis, stability in saline and blood serum, AND charge using paper electrophoresis. Normal biodistribution was studied using a mouse model, while binding affinity with RMS cancer cells was studied using an internalization assay. The in vivo accumulation of RMS cancer cells in a rabbit model was monitored using a SPECT gamma camera. RESULTS: Radiolabeling reaction displayed a pharmaceutical yield of 97% and a stability assay showed >95% intact radiopharmaceutical up to 6 h in saline and blood serum. In vitro internalization studies showed the potential of [99mTc]DTPA-FLUT to enter into cancer cells. This biodistribution study showed rapid blood clearance and minimum uptake by body organs, and scintigraphy displayed the [99mTc]DTPA-FLUT uptake by lesion, induced by RMS cancer cell lines in rabbit. CONCLUSION: Stable, newly developed [99mTc]DTPA-FLUT seeks its way to internalize into RMS cancer cells, indicating it could be a potential candidate for the diagnosis of RMS cancer.

Phytochemicals, Health-Promoting Effects, and Enzyme Inhibition Traits of Phlomis stewartii Extracts.

Phlomis stewartii is a wild, perennial woody plant used for diverse therapeutic targets. The present work evaluated the influence of independent variables such as extraction time, solvent concentration, and speed in the range of (100 mL, 150 mL, and 200 mL), (2 h, 5 h, and 8 h), and (100 rpm, 150 rpm, and 200 rpm), respectively, on extraction yields, phytochemical components, total phenolic contents (TPC), and total flavonoid contents (TFC) of P. stewartii extract. In the present work, response surface methodology (RSM) was applied to optimize the extraction yield. High-performance liquid chromatography (HPLC) was performed to detect the bioactive constituents of the extracts. The potent extracts were analyzed to study α-amylase and α-glucosidase inhibitory activities. Under the optimized conditions of solvent concentration (200 mL), extraction time (8 h), and speed (150 rpm), the whole plant methanol extract (WPME) showed a maximum extraction yield of 13.5%, while the leaves methanol extract (LME) showed a maximum TPC of 19.5 ± 44 mg of gallic acid equivalent (GAE) per gram of extract and a maximum TFC of 4.78 ± 0.34 mg of quercetin equivalent (QE) per gram of extract. HPLC analysis showed the presence of p-coumaric, gallic acid, quercetin, salicylic acid, sinapic acid, and vanillic acid. LME showed the highest α-amylase inhibitory activity (IC50 = 46.86 ± 0.21 µg/mL) and α-glucosidase inhibitory activity (IC50 value of 45.81 ± 0.17 µg/mL). Therefore, in conclusion, LME could be considered to fix the α-amylase and α-glucosidase-mediated disorders in the human body to develop herbal phytomedicine.

Enhancement of photocatalytic activity of Ba-doped CoO for degradation of Emamectin benzoate in aqueous solution.

The present study was focused on the preparation of cobalt oxide (CoO) and barium-doped cobalt oxide (Ba-doped CoO) by following the co-precipitation method for the degradation of Emamectin benzoate pesticide in the aqueous medium. The prepared catalysts were characterized using SEM, EDX, and XRD to confirm the formation of catalysts and to observe the variation in the composition of catalysts during the degradation study. It can be suggested from the results of SEM, EDX, XRD, and FTIR analyses that Ba atom has successfully incorporated in the crystalline structure of CoO. The degradation of Emamectin benzoate pesticide was studied under the influence of different factors like solution pH, the dose of catalyst, contact time, temperature, and initial concentration of pesticide. It was observed that solution pH affects the degradation of the pesticide, and maximum degradation (23% and 54%) was found at pH 5.0 and 6.0 using CoO and Ba-doped CoO, respectively. The degradation of pesticides was found to be increased continuously (27-35% in case of CoO while 47-58% in case Ba-doped CoO) with the time of contact. However, the degradation was found to be decreased (23-3% in case of CoO while 47-44% in case Ba-doped CoO) with an increase in temperature. Likewise, in the beginning, degradation was observed to be increased up to some extent with the dose of catalyst and initial concentration of pesticide but started to decrease with further augmentation in the dose of catalyst and initial concentration of pesticide. It may be concluded from this study that doping of Ba considerably enhanced the photocatalytic ability of CoO for Emamectin benzoate pesticide.

Isolation and characterization of novel antihypertensive bioactive peptides from brassica napus and angiotensin-converting enzyme (ace) inhibition potential.

Present study aimed to explore the antihypertensive potential of bioactive peptides isolated from Brassica napus protein as inhibitor of angiotensin converting enzyme. Protein was extracted and assessed for antihypertensive potential. The extracted protein showed 72% antihypertensive activity/potential with IC50 value of 24±5.60µg/mL. Thirty-one fractions of peptides were isolated by hydrolyzing protein at different time intervals, pH, temperature and enzyme/substrate ratio. The antihypertensive potential of all isolated fractions was measured. It was found that only one peptide fraction exhibited significantly high (75%) antihypertensive potential. This hydrolyzed fraction was characterized through Liquid-Chromatography-Electrospray-Ionization-Mass-Spectrometry (LC-ESI-MS/MS). Eleven bioactive peptides were identified in hydrolyzate of Brassica napus which include Serine-Threonine, Methionine-Valine, Methionine-Leucine, Glutamine-Phenylalanine, Alanine-Threonine-Phenylalanine, Alanine-Leucine-Proline-Glycine, Valine-Alanine-Phenylalanine-Glycine, Aspartic acid-Proline-Methionine-Glutamine, Valine-Glutamine-Cysteine-Tyrosine, Methionine-Cysteine-Tyrosine-Tyrosine-Phenylalanine and Alanine-Leucine-Leucine-Alanine-Cysteine-Proline-Alanine. The current study showed that Brassica napus is an important food, having high amount of bioactive peptides with high antihypertensive potential, can control blood pressure very efficiently.

Synthesis, spectral analysis and biological evaluation of 2-{[(morpholin-4-yl)ethyl]thio}-5-phenyl/aryl-1,3,4-oxadiazole derivatives.

A series of new derivatives of 4-(2-chloroethyl)morpholine hydrochloride (5) were efficiently synthesized. Briefly, different aromatic organic acids (1a-f) were refluxed to acquire respective esters (2a-f) using conc. H2SO4 as catalyst. The esters were subjected to nucleophillic substitution by monohydrated hydrazine to acquire hydrazides (3a-f). The hydrazides were cyclized with CS2 in the presence of KOH to yield corresponding oxadiazoles (4a-f). Finally, the derivatives, 6a-f, were prepared by reacting oxadiazoles (4a-f) with 5 using NaH as activator. Structures of all the derivatives were elucidated through 1D-NMR EI-MS and IR spectral data. All these molecules were subjected to antibacterial and hemolytic activities and showed good antibacterial and hemolytic potential relative to the reference standards.

Potential protective role of curcumin powder to regulate arsenic-induced hepatorenal toxicity and hyperlipidemic metabolic dysfunction in rat model.

The present work was conceptualized to determine the potential protective effects of curcumin on arsenic-induced kidney damage in male albino rat model. Thirty six male albino rats were selected, weighed about 175±10g and classified into four groups (9 rats in each group) such as C group (control with basal diet), Cur group (curcumin 200mg/kg body weight), AI group (arsenic-induced 5mg/kg body weight) and AI + Cur group (arsenic 5mg/kg+curcumin 200mg/kg body weight), respectively. Arsenic and curcumin were offered through the gavage method once daily with basal diet. The different analyzed parameters showed that arsenic-induced elevation of aspartate amino transferase, alkaline phosphatase, bilirubin urea, alanine aminotransferase and creatinine significantly decreased with curcumin application in AI + Cur group. Similarly, the statistically significant decline of low-density lipoprotein (LDL), cholesterol, triglyceride and increased in high-density lipoprotein (HDL) was observed in rats of AI + Cur group with curcumin treatment as compared to the rats of AI group. The level of different enzymes of the liver as well as kidney was noted depleted on arsenic exposure whereas increased in level was observed with curcumin application in AI + Cur group. Moreover, pathological histology changes were also recorded. The outcomes suggest that curcumin has a potential effect against arsenic-induced toxicity in biological model.

Synthesis, evaluation of thymidine phosphorylase and angiogenic inhibitory potential of ciprofloxacin analogues: Repositioning of ciprofloxacin from antibiotic to future anticancer drugs.

Over expression of thymidine phosphorylase (TP) in various human tumors compared to normal healthy tissue is associated with progression of cancer and proliferation. The 2-deoxy-d-ribose is the final product of thymidine phosphorylase (TP) catalyzed reaction. Both TP and 2-deoxy-d-ribose are known to promote unwanted angiogenesis in cancerous cells. Discovery of potent inhibitors of thymidine phosphorylase (TP) can offer appropriate approach in cancer treatment. A series of ciprofloxacin 2, 3a-3c, 4a-4d, 5a-5b, 6 and 7 has been synthesized and characterized using spectroscopic techniques. Afterwards, inhibitory potential of synthesized ciprofloxacin 2, 3a-3c, 4a-4d, 5a-5b, 6 and 7 against thymidine phosphorylase enzyme was assessed. Out of these twelve analogs of ciprofloxacin nine analogues 3a-3c, 4a-4c, 5a-5b and 6 showed good inhibitory activity against thymidine phosphorylase. Inhibitory activity as presented by their IC50 values was found in the range of 39.71 ± 1.13 to 161.89 ± 0.95 µM. The 7-deazaxanthine was used as a standard inhibitor with IC50 = 37.82 ± 0.93 µM. Furthermore, the chick chorionic allantoic membrane (CAM) assay was used to investigate anti-angiogenic activity of the most active ciprofloxacin-based inhibitor 3b. To enlighten the important binding interactions of ciprofloxacin derivatives with target enzyme, the structure activity relationship and molecular docking studies of chosen ciprofloxacin analogues was discussed. Docking studies revealed key π-π stacking, π-cation and hydrogen bonding interactions of ciprofloxacin analogues with active site residues of thymidine phosphorylase enzyme.

5-Endo-dig cyclizations in organic syntheses.

The favorability of ring closure reactions as per Baldwin rules has gained immense importance recently. This is evident from the current literature such as research articles, reviews, and books that have been published in this area. This review covers the recent applications of 5-endo-dig cyclization in organic synthesis focusing in the last two decades. A variety of 5-membered heterocycles as well as carbocycles could be synthesized via 5-endo-dig cyclization reactions. The important applications of 5-endo-dig cyclization in organic synthesis covering different aspects have been summarized in this review.

Calotropis procera (root) escalates functions rehabilitation and attenuates oxidative stress in a mouse model of peripheral nerve injury.

Peripheral nerve injuries result in sensorimotor functional loss, leading to permanent disability and physical dependency with immense cost and reduced quality of life. These injuries are among those complicated medical situations which still are waiting for their first-line treatment. This study was designed to investigate the role of Calotropis procera (crude roots) in accelerating functional retrieval following mechanically induced sciatic nerve injury in healthy albino male mice. Following acclimatization, mice were grouped equally as "Control" fed on normal chow and "Root" fed on C. procera root (100mg/kg/day) mixed chow. A mechanical crush was induced in right sciatic nerve of animals. Behavioral analyses (grip strength, SFI, pinprick and hot plate tests) were conducted for assessing sensorimotor function reclamation and blood was collected for oxidative stress assessment. Significantly earlier retrieval of sensorimotor activities (p<0.05), reduced total oxidant status, increased total antioxidant capacity with prominently enhanced arylesterase and paraoxonase activities (p<0.001) in treatment group suggested positive impact of C. procera roots on quickening functional recovery and combating oxidative stress following nerve injury. Thus C. procera root can be considered as potential candidate drug for further investigation to seek bioactive compound/s that may actually responsible for ameliorative functional recovery following nerve injury.

Technetium-99m labeled Ibuprofen: Development and biological evaluation using sterile inflammation induced animal models.

In this study we are presenting the development of technetium-99m (99mTc) labeled ibuprofen for the imaging of aseptic inflammation. 99mTc-Ibuprofen complex was developed by optimizing the radiolabeling conditions such as reaction time, ligand and reducing agent concentration, pH, reaction time and temperature. Following the addition of 600 µg of ibuprofen, 4 µg of stannous chloride as reducing agent and 300 MBq 99mTc radioactivity; the pH of reaction mixture was adjusted to 11 and allowed to react for 15 min at room temperature. Chromatography analysis revealed > 94% 99mTc-ibuprofen complex formation with promising stability in saline and blood serum up to 6 h. Biodistribution study using normal and sterile inflammation induced mice indicated low accumulation of labeled compound in key body organs; however, kidneys (14.76 ± 0.87% ID/g organ) and bladder (31.6 ± 3.0% ID/g organ) showed comparatively higher radioactivity due to main excretory path. Inflamed to normal tissues ratio (T/NT), at 1 h post-injection, showed promising value (4.57 ± 0.56). The SPECT imaging of artificially inflammation induced rabbit model also verified the biodistribution results. In conclusion, radiochemical purity and biological evaluation of 99mTc-ibuprofen complex indicates the agent can be utilized for imaging of deep seated aseptic inflammation.

Identification of 1,2,4-triazoles as new thymidine phosphorylase inhibitors: Future anti-tumor drugs.

Thymidine phosphorylase (TP) is over expressed in several solid tumors and its inhibition can offer unique target suitable for drug discovery in cancer. A series of 1,2,4-triazoles 3a-3l has been synthesized in good yields and subsequently inhibitory potential of synthesized triazoles 3a-3l against thymidine phosphorylase enzyme was evaluated. Out of these twelve analogs five analogues 3b, 3c, 3f, 3l and 3l exhibited a good inhibitory potential against thymidine phosphorylase. Inhibitory potential in term of IC50 values were found in the range of 61.98 ±â€¯0.43 to 273.43 ±â€¯0.96 µM and 7-Deazaxanthine was taken as a standard inhibitor with IC50 = 38.68 ±â€¯4.42 µM. Encouraged by these results, more analogues 1,2,4-triazole-3-mercaptocarboxylic acids 4a-4g were synthesized and their inhibitory potential against thymidine phosphorylase was evaluated. In this series, six analogues 4b-4g exhibited a good inhibitory potential in the range of 43.86 ±â€¯1.11-163.43 ±â€¯2.03 µM. Angiogenic response of 1,2,4-triazole acid 4d was estimated using the chick chorionic allantoic membrane (CAM) assay. In the light of these findings, structure activity relationship and molecular docking studies of selected triazoles to determine the key binding interactions was discussed. Docking studies demonstrate that synthesized analogues interacted with active site residues of thymidine phosphorylase enzyme through π-π stacking, thiolate and hydrogen bonding interactions.

Synthetic applications and methodology development of Chan-Lam coupling: a review.

Chan-Lam coupling is one of the most popular and easy methods to perform arylation of amines (N-arylations). This cross-coupling is generally performed by reacting aryl boronate derivatives with a variety of substrates involving nitrogen containing functional groups such as amines, amides, ureas, hydrazine, carbamates. This article summarizes the synthetic applications of this reaction and the efforts of scientists to develop novel and efficient methodologies for this reaction.

Purification and modification of Cordia myxa gum to enhance its nutraceutical attribute as binding agent.

The aim of the present study was to purify, hydrolyze and modify the Cordia myxa gum to document its binder potential in pharmaceutical tablets formulation. The hydrolysis and modification was carried out to remove impurities, roughness, increase thermal stability and to improve the functional properties of biopolymers. Physiochemical properties such as pH, solubility, viscosity, swelling index, bulk and tapped density was performed prior to investigate binder potential. The binder potential of Cordia myxa gum was studied in its different forms such as crude, purified, modified and hydrolyzed in paracetamol tablets and was compared with standard hydroxypropyl methylcellulose (HPMC) being used as synthetic binder. Tablets were prepared by direct compression method and evaluated for weight uniformity, hardness, friability, disintegration time and dissolution analysis. Prepared tablets with selected gums exhibit faster and slower dissolution profile in the same dissolution system. The crude gum has high dissolution rate whereas the hydrolyzed and modified gums showed less dissolution rate. The hydrolyzed and modified gums having faster release rate and it could be helpful in conventional tablet formulations efficiently as compared to synthetic HPMC binder.

Detection of Paracetamol as substrate of the gut microbiome.

Gut microbiome, a new organ; represent targets to alter pharmacokinetics of orally administered drugs. Recently, in vitro trials endorsed the idea that orally administered drugs interact and some of their quantity may be taken up by normal microbiome during transit through gut. Such transport mechanisms in microbiome may compete for drug with the host itself. Currently, no data confirms specific transport system for paracetamol uptake by gut microbiome. In vivo trial was conducted in normal healthy male rats (n=36). Paracetamol was administered orally in a single dose of 75mg/kg to isolate microbial mass after transit of 2, 3, 4, 5 and 6 hours post drug administration. Paracetamol absorbance by microbiome was pursued by injecting extracted microbial lysate in RP-HPLC-UV with C18 column under isocratic conditions at 207nm using acetonitrile and water (25:75 v/v) pH 2.50 as mobile phase. Paracetamol absorbance (14.10±0.75µg/mg of microbial mass) and percent dose recovery (13.16±0.55%) seen at transit of 4 hours was significantly higher (P<0.05) compared to other groups. Study confirms the hypothesis of homology between membrane transporters of the gut microbiome and intestinal epithelium. Orally administered drugs can be absorbed by gut microbes competitively during transit in small intestine and it varies at various transit times.

177Lu-DOTA-coupled minigastrin peptides: promising theranostic agents in neuroendocrine cancers.

Treatment with radionuclide labeled regulatory peptides is a promising tool in the management of patients with inoperable receptor positive neuroendocrine tumors. Peptide receptor lutetium-177 radionuclide therapy currently has gained ample attention due to high specific accumulation of regulatory peptides at tumor cell surface and promising characteristics of ß- and γ-energy photons of lutetium-177 radionuclide. In this study gastrin peptides analogues were labeled with lutetium-177 by subsequent mixing of 177LuCl3 (~ 185 MBq), ammonium acetate buffer of 5 pH, gentistic acid, aqueous solution of gastrin peptide analogues (1 mg/mL) and heating the reaction mixture at 98 °C which resulted in high radiochemical yield (> 96%). Chromatographic analysis was carried out to analyze the radiochemical purity. The shelf life and serum stability results showed the labeled peptides are sufficiently stable up to 4-h. Glomerular filtration rate study results showed moderate filtration through kidneys. The GFR values of 177Lu-MGCL2 and 177Lu-MGCL4 was noted 48 mL/min and 45 mL/min, respectively. Biodistribution and scintigraphy study using rat and rabbit models showed minimal non-target accumulation, moderate uptake by liver and kidneys. The promising radiochemical yield, stability, GFR values and biodistribution results of 177Lu-MGCL2 & 4 indicate, the agents can be tested clinically for PRRT procedures.

Ciprofloxacin: from infection therapy to molecular imaging.

Diagnosis of deep-seated bacterial infection remains a serious medical challenge. The situation is becoming more severe with the increasing prevalence of bacteria that are resistant to multiple antibiotic classes. Early efforts to develop imaging agents for infection, such as technetium-99m (99mTc) labeled leukocytes, were encouraging, but they failed to differentiate between bacterial infection and sterile inflammation. Other diagnostic techniques, such as ultrasonography, magnetic resonance imaging, and computed tomography, also fail to distinguish between bacterial infection and sterile inflammation. In an attempt to bypass these problems, the potent, broad-spectrum antibiotic ciprofloxacin was labeled with 99mTc to image bacterial infection. Initial results were encouraging, but excitement declined when controversial results were reported. Subsequent radiolabeling of ciprofloxacin with 99mTc using tricarbonyl and nitrido core, fluorine and rhenium couldn't produce robust infection imaging agent and remained in discussion. The issue of developing a robust probe can be approached by reviewing the broad-spectrum activity of ciprofloxacin, labeling strategies, potential for imaging infection, and structure-activity (specificity) relationships. In this review we discuss ways to accelerate efforts to improve the specificity of ciprofloxacin-based imaging.

Recent trends in ring opening of epoxides with sulfur nucleophiles.

Thiolysis of epoxides offers an efficient and simple synthetic approach to access [Formula: see text]-hydroxy sulfides which are valuable scaffold in the synthesis of various important molecules in medicinal chemistry. This review article presents a recent compilation of the synthetic approaches developed after 2000 for the thiolysis of epoxides.

Nucleophilic ring opening reactions of aziridines.

Aziridine ring opening reactions have gained tremendous importance in the synthesis of nitrogen containing biologically active molecules. During recent years, a great effort has been put forward by scientists toward unique bond construction methodologies via ring opening of aziridines. In this regard, a wide range of chiral metal- and organo-catalyzed desymmetrization reactions of aziridines have been reported with carbon, sulfur, oxygen, nitrogen, halogen, and other nucleophiles. In this review, an outline of methodologies adopted by a number of scientists during 2013-2017 for aziridine ring opening reactions as well as their synthetic applications is described.

Phenolic acid profiling and antiglycation studies of leaf and fruit extracts of tyrosine primed Momordica charantia seeds for possible treatment of diabetes mellitus.

The increasing risk of variety of fatal diseases including diabetes mellitus is imposing serious challenge to chemist, biologists and clinicians. Due to the side effects of the chemotherapy, worldwide it is thinking that phyto-medicine are more effective to cope continuously increasing risk of fatal diseases without any side effect. Seed priming is a strategic pre-sowing semi-bioengineering technique which has ability to improve the growth rate and biologically active compounds in short time. Among seed priming techniques, tyrosine seed priming most frequently used because amino acids provide best growth media for nutritional food crops. Seeds of Momordica charantia were subjected to the pre-sowing tyrosine solution. Different growth parameters including growth emergence rate, seedling vigor, growth and weight of root, shoot and leaf were studied. The results showed positive effect on Momordica charantia seed growth and phenolic acids production i.e. ferulic acid - 43.95 ppm and sinapic acid - 18.39 ppm. The antiglycation assay showed 23.45±1.23% antiglycation activity of primed-seed fruit extract as compare to control seed fruit extract (0.87±0.03%). On the basis of the results, it is concluded that tyrosine primed seed fruit extract could effectively be further tested for pre-clinical and clinical studies to manage diabetes mellitus disease.

Biosurfactants production potential of native strains of Bacillus cereus and their antimicrobial, cytotoxic and antioxidant activities.

Present study was designed to evaluate the biosurfactant production potential by native strains of Bacillus cereus as well as determine their antimicrobial and antioxidant activities. The strains isolated from garden soil were characterized as B. cereus MMIC 1, MMIC 2 and MMIC 3. Biosurfactants were extracted as grey white precipitates. Optimum conditions for biosurfactant production were 37°C, the 7th day of incubation, 0.5% NaCl, pH 7.0. Moreover, corn steep liquor was the best carbon source. Biuret test, Thin Layer Chromatography (TLC), agar double diffusion and Fourier Transform Infrared Spectroscopy (FTIR) characterized the biosurfactants as cationic lipopeptides. Biosurfactants exhibited significant antibacterial and antifungal activity against S. aureus, E. coli, P. aeruginosa, K. pneumoniae, A. niger and C. albicans at 30 mg/ml. Moreover, they also possessed antiviral activity against NDV at 10 mg/ml. Cytotoxicity assay in BHK-21 cell lines revealed 63% cell survival at 10 mg/ml of biosurfactants and thus considered as safe. They also showed very good antioxidant activity by ferric-reducing activity and DPPH scavenging activity at 2 mg/ml. Consequently, the study offers an insight for the exploration of new bioactive molecules from the soil. It was concluded that lipopeptide biosurfactants produced from native strains of B. cereus may be recommended as safe antimicrobial, emulsifier and antioxidant agent.