Diuretic and antilithiasic activities of ethanolic extract from Piper amalago (Piperaceae)

ObjectivePiper amalago is used in Brazilian folk medicine as diuretic and for the treatment of urinary calculus disease, although no scientific data have been described to support these effects. Thus, this study aims to evaluate the diuretic effects and antilithiatic activity of the ethanolic extract of P. amalago (EEPam).Materials and methodsEthanolic extracts of P. amalago (125, 250 and 500 mg/kg) were orally administered in male Wistar rats (n = 5) and urinary excretion was measured at intervals of up to 24 h after administration. The antilithiasic effect of EEPam on calcium oxalate urolithiasis crystallization was examined in a turbidimetric model.ResultsThe oral administration of all doses of EEPam significantly increased urine output after 24 h when compared to control group. Moreover, the application of EEPam, induced an inhibitory effect on calcium oxalate crystallization.ConclusionsAccording to results, P. amalago extracts showed diuretic and natriuretic activity and antilithiasic effects.     

Urine nitrification with a synthetic microbial community

During long-term extra-terrestrial missions, food is limited and waste is generated. By recycling valuable nutrients from this waste via regenerative life support systems, food can be produced in space. Astronauts’ urine can, for instance, be nitrified by micro-organisms into a liquid nitrate fertilizer for plant growth in space. Due to stringent conditions in space, microbial communities need to be be defined (gnotobiotic); therefore, synthetic rather than mixed microbial communities are preferred. For urine nitrification, synthetic communities face challenges, such as from salinity, ureolysis, and organics.In this study, a synthetic microbial community containing an AOB (Nitrosomonas europaea), NOB (Nitrobacter winogradskyi), and three ureolytic heterotrophs (Pseudomonas fluorescens, Acidovorax delafieldii, and Delftia acidovorans) was compiled and evaluated for these challenges. In reactor 1, salt adaptation of the ammonium-fed AOB and NOB co-culture was possible up to 45 mS cm⁻¹, which resembled undiluted nitrified urine, while maintaining a 44 ± 10 mg NH₄⁺–N L⁻¹ d⁻¹ removal rate. In reactor 2, the nitrifiers and ureolytic heterotrophs were fed with urine and achieved a 15 ± 6 mg NO₃⁻–N L⁻¹ d⁻¹ production rate for 1% and 10% synthetic and fresh real urine, respectively. Batch activity tests with this community using fresh real urine even reached 29 ± 3 mg N L⁻¹ d⁻¹. Organics removal in the reactor (69 ± 15%) should be optimized to generate a nitrate fertilizer for future space applications.     

Analysis of cyclosporine A and its metabolites in rat urine and feces by liquid chromatography–tandem mass spectrometry

A sensitive and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for the quantification of cyclosporine A (CyA) and the identification of its metabolites in rat urine and feces. The analytes were extracted from waste samples via liquid–liquid extraction. A Turboionspray source was used as a detector. It was operated in a positive ion mode with transitions of m/z 1225 → m/z 1112 for CyA and in a selected multiple reactions monitoring (MRM) mode with transitions of m/z 1239 → m/z 1099 for the internal standard (cyclosporine D, CyD). Linear calibration curves were obtained for CyA concentration ranges of 12.5–250 ng mL^?1 in urine and 2.5–375 ng mg^?1 in feces. The intra- and inter-day precision values (relative standard deviation) obtained were less than 8%, and the accuracy was within ±15% for each of the analytes. Extraction recoveries of CyA and CyD were both over 80%. The identification of the metabolites and elucidation of their structure were performed on the basis of their retention times and mass spectrometry fragmentation behaviors. A total of seven metabolites in rat feces were identified as dimethyl CyA, hydroxy CyA, and dihydroxy CyA after the oral administration of cyclosporine A-Eudragit^® S100 nanoparticles (CyA-NP). Six of these metabolites were also detected in rat urine. A possible metabolic pathway was also proposed. The newly developed method was proven to be sensitive, simple, reproducible, and suitable for the rapid determination of CyA. It was successfully employed to study the excretion of CyA in rats and could be used to better understand the in vivo metabolism of CyA-NP, a potentially effective nanoparticle system.     

Quantitative determination of helicid in rat biosamples by liquid chromatography electrospray ionization mass spectrometry

A simple liquid chromatography electrospray ionization mass spectrometry (LC–ESI–MS) method with highly improved sensitivities for the determination of helicid in rat bile, urine, feces and most tissues was developed. The tissues and feces were firstly homogenized mechanically using deionized water as the media. Bile, urine, tissues and feces homogenates were extracted by liquid–liquid extraction with n-butyl alcohol for sample preparation. The subsequent analysis procedures were performed on a Shimadzu LCMS2010A system (electrospray ionization single quadrupole mass analyzer). A Luna C₁₈ column (150 mm × 2.00 mm, 5 μm) was used as the analytical column, while a mixture of acetonitrile and ammonium chloride water solution was used as the mobile phase. The proportions of mobile phase were changed timely according to gradient programs. Chlorinated adducts of molecular ions [M+Cl]^? at m/z 319.00 and 363.05 were used to quantify helicid and bergeninum (internal standard), respectively. The method was validated to be accurate, precise and rugged with good linearity. The proposed method was successfully applied to the preclinical tissue distribution and excretion studies of helicid in rats.     

Effects of Canarium odontophyllum leaves on plasma glucose and T lymphocyte population in streptozotocin-induced diabetic rats

Type 1 diabetes mellitus is a chronic disease characterized by lack of insulin production. Immune mechanisms are implicated in the pathogenesis of Type 1 diabetes. Canarium odontophyllum (CO) fruits and leaves have been shown to possess high antioxidant activity. This study was conducted to evaluate the effects of CO leaves aqueous extract on the blood glucose and T lymphocyte population in the spleen of streptozotocin (STZ)-induced diabetic rats. Nineteen male Sprague–Dawley rats were randomly divided into three groups: normal, diabetic control and CO treated diabetic groups. Diabetes was induced by a single intraperitoneal injection of 65 mg STZ/kg body weight. The extract of CO leaves was administered orally by force feeding daily at the dose of 300 mg/kg for 28 days. The rats were sacrificed at the end of the study and the spleen was harvested for flow cytometry analysis. The results showed a significant decrease in body weight of diabetic and CO treated diabetic groups compared with the normal group (p < 0.05). The fasting blood glucose level of CO treated diabetic group was significantly lower than the diabetic group (p < 0.05). Diabetic and CO treated diabetic groups showed a significant increase in the percentage of spleen CD3⁺ CD4⁺ T lymphocytes (p < 0.05) when compared with the normal group. However, there was no significant difference in the percentage of spleen CD3⁺ CD8⁺ T lymphocytes among all experimental groups. The finding suggested that an aqueous extract of CO leaves has the ability to reduce blood glucose levels in diabetic rats.     

Identification and simultaneous determination of p-FHA and p-FBA,two metabolites of anti-tumor agent—Fluorapacin in rat urine

Fluorapacin, bis(4-fluorobenzyl)trisulfide, a small molecule natural product derivative of trisulfide, has revealed a broad spectrum of anti-proliferative activity and in vivo anti-tumor efficacy in human xenograft mice models with excellent safety profile. In the present study, two new metabolites, para-fluorohippuric acid (p-FHA) and para-fluorobenzoic acid (p-FBA), were identified by GC–MS and HPLC as the main metabolites in urine of rats after intravenous administration of fluorapacin. A simple HPLC-UV method for simultaneous determination of these two metabolites in urine has been developed and validated. The newly developed method demonstrated excellent specificity, accuracy, precision, and stability. This method was successfully employed to study the urinary excretion of fluorapacin in rats. The results indicated that p-FHA was the major metabolite in urine, and the total excretion recovery of p-FHA and p-FBA was 67.6 ± 4.9% (mean ± SE, n = 6) of dosage after 48 h of administration.     

Extraction of trace amounts of pioglitazone as an anti-diabetic drug with hollow fiber liquid phase microextraction and determination by high-performance liquid chromatography-ultraviolet detection in biological fluids

The applicability of hollow fiber liquid phase microextraction (HF-LPME) for extraction and preconcentration of trace amounts of pioglitazone (PGL) as an anti-diabetic drug in biological fluids, prior to determination by high-performance liquid chromatography (HPLC), was evaluated. In this technique, the target drug was extracted into di-n-hexyl ether immobilized in the wall pores of a porous hollow fiber from 10 mL of the aqueous sample (source phase, SP) with pH 8.0, and then back extracted into the receiving phase (RP) with pH 2.2 located in the lumen of the hollow fiber. The extraction occurred due to a pH gradient between the two sides of the hollow fiber. After extracting for a prescribed time, 24 μL of the RP solution was taken back into the syringe and injected directly into a HPLC instrument for quantification. The Taguchi orthogonal array (OAD) experimental design with an OA₁₆ (4⁵) matrix was employed to optimize the HF-LPME conditions. Different factors affecting the HF-LPME efficiency such as the nature of organic solvent used to impregnate the membrane, pH of the SP and RP, stirring speed, extraction time and ionic strength were studied and optimized. Under the optimum conditions (di-n-hexyl ether as membrane impregnation solvent, pHs of the SP and RP equal to 8.0 and 2.2, respectively, extraction time of 30 min, stirring speed of 500 rpm and 10% (w/v) NaCl for adjusting the ionic strength), preconcentration factor of 180, linear dynamic range (LDR) of 2.5–250 μg L^?1 with good correlation of determination (r² > 0.998) and limit of detection (LOD) of 1.0 μg L^?1 were obtained for the target drug. The percent relative intra-day and inter-day standard deviations (RSDs%) based on five replicate determinations were 4.7 and 15%, respectively. Once LPME was optimized, the performance of the proposed technique was evaluated for the determination of PGL in different types of biological fluids such as plasma and urine samples. The results showed that the proposed HF-LPME method could be successfully applied to determine trace amounts of PGL in biological samples.     

Effects of praeruptorin C on blood pressure and expression of phospholamban in spontaneously hypertensive rats

BackgroundThe traditional Chinese medicine Praeruptorin c (Pra-c) has many physiological and pharmacological effects, including antagonistic effects on blood pressure and calcium levels, maintenance of cellular calcium homeostasis, and improved cardiac systolic and diastolic function. It is potentially a novel and versatile drug for the treatment and prevention of cardiovascular diseases.ObjectiveTo explore the possible impact of Pra-c on blood pressure in SHR and its mechanism of action.Materials and methodsTwenty SHR were randomly divided into a Pra-c group [Pra-c was administered intragastrically, 20 mg kg⁻¹ d⁻¹, n = 10] or an untreated control group (n = 10), containing 10 age-matched SD rats. Each group of rats was followed for 8 weeks. Before and during the treatment, tail artery systolic blood pressure was measured using a tail-cuff every 2 weeks. After 8 weeks, the rats were sacrificed and RNA was extracted from homogenates of cardiac tissue. Tissue from the left ventricle was fixed, sectioned and H&E stained to assess possible changes in myocardial cell structure and morphology. Semi-quantitative RT-PCR was used to assess changes in phospholamban gene expression in treated and untreated rats.ResultsSHR treated with Pra-c for 8 weeks had a lower systolic pressure than untreated SHR (p < 0.05), two measures of cardiac damage, the heart mass index and left ventricle mass index (HMI and LVMI, respectively) were improved, and the level of PLB mRNA expression was lower in the untreated SHR group (p < 0.05).Discussion and conclusionWith continuous hypertension, SHR gradually formed or developed cardiac hypertrophy and fibrosis. Pra-c had a clear effect on blood pressure in SHR, and reversed SHR ventricular remodeling by upregulating the gene expression of sarcoplasmic reticulum PLB.     

3′,4′-Bis-difluoromethoxycinnamoylanthranilate (FT061): An orally-active antifibrotic agent that reduces albuminuria in a rat model of progressive diabetic nephropathy

Cinnamoylanthranilates including tranilast have been identified as promising antifibrotics that can reduce fibrosis occurring in the kidney during diabetes, thereby delaying and/or preventing kidney dysfunction. Structure–activity relationships aimed at improving potency and metabolic stability have led to the discovery of FT061. This compound, which bears a bis-difluoromethoxy catechol, attenuates TGF-β-stimulated production of collagen in cultured renal mesangial cells (approx 50% at 3 μM). When dosed orally at 20 mg/kg to male Sprague Dawley rats, FT061 exhibited a high bioavailability (73%), C_max of 200 μM and T_max of 150 min, and a half-life of 5.4 h. FT061 reduced albuminuria when orally dosed in rats at 200 mg kg/day in a late intervention study of a rat model of progressive diabetic nephropathy.     

Urine as a material for evaluation of exposure to manganese in methcathinone users

Chronic exposure even to low doses of manganese may lead to development of neurological syndrome similar to parkinsonism. The aim of this research is to assess the possibility of manganese poisoning based on the level of metal in the urine of long-term methcathinone users from Poland. Graphite furnace atomic absorption spectroscopy (GFAAS) was used to determine manganese in urine, while the detection of the psychoactive drugs was performed by high-performance liquid chromatography (HPLC). Results of survey on longitudinal patterns of drug use showed that users of traditional illicit drugs now turn to cheaper alternatives, such as methcathinone. Parkinsonian features were observed in almost half of methcathinone users. The subjects had a higher mean level of Mn in their urine (8.68 ± 9.27 μg L⁻¹) than the controls (4.27 ± 1.91 μg L⁻¹). The presence of numerous psychoactive substances (in unchanged forms and their metabolites) was confirmed in all of the samples, with only one exception. The elevated level of manganese in urine (in 29.2% of patients) can be used as a primary marker of recent methcathinone administration, especially in the case of long time intravenous drug users where blood sampling is complicated.     

Determination of phenothiazine derivatives in human urine by using ionic liquid-based dynamic liquid-phase microextraction coupled with liquid chromatography

A simple and rapid method for the determination of seven phenothiazines derivatives (chlorpromazine, promethazine, levomepromazine, prochlorperazine, trifluoperazine, fluphenazine and thioridazine) in human urine samples is presented. The analytes are extracted from the sample in 50 μL of the ionic liquid 1-butyl-3-methyl-imidazolium hexafluorophosphate working in an automatic flow system under dynamic conditions. The chemical affinity between the extractant and the analytes allows a good isolation of the drugs from the sample matrix achieving at the same time their preconcentration. The separation and detection of the extracted compounds is accomplished by liquid chromatography and UV detection. The proposed method is a valuable alternative for the analysis of these drugs in urine within the concentration range 0.07–10 μg mL^?1. Limits of detection were in the range from 21 ng mL^?1 (thioridazine) to 60 ng mL^?1 (levomepromazine). The repeatability of the proposed method expressed as RSD (n = 5) varied between 2.2% (levomepromazine) and 3.9% (chlorpromazine).     

Capillaria plica (syn. Pearsonema plica) infection in a dog with chronic pollakiuria: Challenges in the diagnosis and treatment

Capillaria plica (syn. Pearsonema plica) is a nematode parasite of the urinary tract of canids, felids and mustelids, which can cause cystitis, pollakiuria, dysuria and hematuria. An eight-month-old female crossbred dog from Switzerland presented a six-month history of frequent urination. During the first clinical examination, C. plica eggs were detected in the urine sediment. Three series of treatments with fenbendazole (50 mg/kg body weight [BW]/day, orally) for 10 days each, three single day treatments with moxidectin–imidacloprid (spot-on) and one single administration of ivermectin (0.2 mg/kg BW subcutaneously) were performed within an eight-month period. None of those treatments succeeded in eliminating the C. plica infection or in resolving the clinical signs. An endoscopic examination of the urine bladder still revealed numerous adult viable C. plica worms attached to the bladder mucosa. A two-day treatment with levamisole (7.5 mg/kg BW/day intramuscularly) was subsequently performed. An endoscopic control of the urine bladder two days after this treatment and a urine analysis after two weeks confirmed the elimination of the parasites. The clinical signs disappeared within one month. Levamisole was shown to be effective against C. plica infection in a dog, whereas previous treatments with fenbendazole, moxidectin and ivermectin had failed.     

Exenatide-loaded PLGA microspheres with improved glycemic control: In vitro bioactivity and in vivo pharmacokinetic profiles after subcutaneous administration to SD rats

A subcutaneous exenatide delivery system was developed and characterized in vitro and in vivo. The results clearly showed that the exenatide loaded PLGA microspheres prepared by using a non-aqueous processing medium had low burst release and high drug encapsulation efficiency. Exenatide loaded in the microspheres preserved its bioactivity. The pharmacokinetics parameters were determined after subcutaneous administration of microspheres to SD rats. The plasma concentration of the single dose of the sustained-release microspheres attained C_max of 108.19 ± 14.92 ng/ml at t_max of 1.33 ± 0.58 h and the t_1/2 was 120.65 ± 44.18 h. There was a linear correlation between the in vitro and in vivo release behavior (R² = 0.888). Exenatide loaded microspheres may prove to have great potential for clinical use.     

Syntheses and pharmacological characterization of novel thiazole derivatives as potential mGluR5 PET ligands

Four novel thiazole containing ABP688 derivatives were synthesized and evaluated for their binding affinity towards the metabotropic glutamate receptor subtype 5 (mGluR5). (E)-3-((2-(Fluoromethyl)thiazol-4-yl)ethynyl)cyclohex-2-enone O-methyl oxime (FTECMO), the ligand with the highest binding affinity (K_i = 5.5 ± 1.1 nM), was labeled with fluorine-18. [¹⁸F]-FTECMO displayed optimal lipophilicity (log D_pH7.4 = 1.6 ± 0.2) and high stability in rat and human plasma as well as sufficient stability in rat liver microsomes. In vitro autoradiography with [¹⁸F]-FTECMO revealed a heterogeneous and displaceable binding in mGluR5-rich brain regions. PET imaging with [¹⁸F]-FTECMO in Wistar rats, however, showed low brain uptake. Uptake of radioactivity into the skull was observed suggesting in vivo defluorination. Thus, although [¹⁸F]-FTECMO is an excellent ligand for the detection of mGluR5 in vitro, its in vivo characteristics are not optimal for the imaging of mGluR5 in rats in vivo.     

Plasma levels of intermedin (adrenomedullin-2) in healthy human volunteers and patients with heart failure

Intermedin/adrenomedullin-2 (IMD) is a member of the adrenomedullin/CGRP peptide family. Less is known about the distribution of IMD than for other family members within the mammalian cardiovascular system, particularly in humans. The aim was to evaluate plasma IMD levels in healthy subjects and patients with chronic heart failure. IMD and its precursor fragments, preproIMD_25–56 and preproIMD_57–92, were measured by radioimmunoassay in 75 healthy subjects and levels of IMD were also compared to those of adrenomedullin (AM) and mid-region proadrenomedullin_45–92 (MRproAM_45–92) in 19 patients with systolic heart failure (LVEF < 45%). In healthy subjects, plasma levels (mean + SE) of IMD (6.3 + 0.6 pg ml⁻¹) were lower than, but correlated with those of AM (25.8 + 1.8 pg ml⁻¹; r = 0.49, p < 0.001). Plasma preproIMD_25–56 (39.6 + 3.1 pg ml⁻¹), preproIMD_57–92 (25.9 + 3.8 pg ml⁻¹) and MRproAM_45–92 (200.2 + 6.7 pg ml⁻¹) were greater than their respective bioactive peptides. IMD levels correlated positively with BMI but not age, and were elevated in heart failure (9.8 + 1.3 pg ml⁻¹, p < 0.05), similarly to MRproAM_45–92 (329.5 + 41.9 pg ml⁻¹, p < 0.001) and AM (56.8 + 10.9 pg ml⁻¹, p < 0.01). IMD levels were greater in heart failure patients with concomitant renal impairment (11.3 + 1.8 pg ml⁻¹) than those without (6.5 + 1.0 pg ml⁻¹; p < 0.05). IMD and AM were greater in patients receiving submaximal compared with maximal heart failure drug therapy and were decreased after 6 months of cardiac resynchronization therapy. In conclusion, IMD is present in the plasma of healthy subjects less abundantly than AM, but is similarly correlated weakly with BMI. IMD levels are elevated in heart failure, especially with concomitant renal impairment, and tend to be reduced by high intensity drug or pacing therapy.     

Comparative studies on dry matter intake,digestibility and nitrogen metabolism between Thai native (TN) and Anglo Nubian × TN bucks

Metabolic experiments were conducted for each Thai native (TN) and Anglo Nubian–TN 50% (AN × TN) bucks, 26.5–38 kg BW and 35–52 months of age, by assigning the following concentrate diets, which had four levels of CP concentrations, T1: 14%, T2: 21%, T3: 28% and T4: 35%, on a DM basis. The animals were fed the concentrates at a rate of 1% of their BW and had ad libitum access to Paspalum plicatulum hay. As the CP level increased, digestibility of CP, N excretion in urine and N retention increased (P < 0.01). No significant differences of DM digestibility among the CP levels of diet and between the breeds of bucks were observed. The AN × TN had higher DM intake than TN (P < 0.05, 40.9 g/(kg BW^0.75 day) versus 36.0 g/(kg BW^0.75 day)), thus N intake of AN × TN was higher than that of TN (P < 0.01, 0.99 g/(kg BW^0.75 day) versus 0.90 g/(kg BW^0.75 day)). Digestibility of CP and blood urea N concentrations of TN were higher than those of AN × TN (P < 0.05, 69.8% versus 64.0% and 32.2 mg/dl versus 26.7 mg/dl, respectively). The AN × TN tended to retain more N than TN in the higher CP feeding condition of T3 (0.19 g/(kg BW^0.75 day) versus 0.11 g/(kg BW^0.75 day)) and T4 (0.25 g/(kg BW^0.75 day) versus 0.17 g/(kg BW^0.75 day)). Digestibility of NDF and ADF, and TDN of TN were higher than those of AN × TN (P < 0.05, 61.1% versus 55.9%, 49.6% versus 43.5% and 65.8% versus 62.4%, respectively). The overall mean DE was 109 kcal/(kg BW^0.75 day), and no significant difference of DE among CP levels nor breeds of bucks was observed. Thai native was superior to AN × TN in digestibility of N and fiber fractions at the maintenance level of DE, which might have overcome inferiority of TN to AN × TN in amount of N and energy intake caused by the lower DMI. It is likely that TN goats are well adapted to fodder shortage condition due to their efficient utilization of nutrients.     

Evaluation of (Z)-2-((1-benzyl-1H-indol-3-yl)methylene)-quinuclidin-3-one analogues as novel,high affinity ligands for CB1 and CB2 cannabinoid receptors

A small library of N-benzyl indolequinuclidinone (IQD) analogs has been identified as a novel class of cannabinoid ligands. The affinity and selectivity of these IQDs for the two established cannabinoid receptor subtypes, CB1 and CB2, was evaluated. Compounds 8 (R = R² = H, R¹ = F) and 13 (R = COOCH₃, R¹ = R² = H) exhibited high affinity for CB2 receptors with K_i values of 1.33 and 2.50 nM, respectively, and had lower affinities for the CB1 receptor (K_i values of 9.23 and 85.7 nM, respectively). Compound 13 had the highest selectivity of all the compounds examined, and represents a potent cannabinoid ligand with 34-times greater selectivity for CB2R over CB1R. These findings are significant for future drug development, given recent reports demonstrating beneficial use of cannabinoid ligands in a wide variety of human disease states including drug abuse, depression, schizophrenia, inflammation, chronic pain, obesity, osteoporosis and cancer.     

Synthesis and characterization of 123I-CMICE-013: A potential SPECT myocardial perfusion imaging agent

Coronary artery disease (CAD) is a major cause of death in Canada and the United States. Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a useful diagnostic test in the management of patients with CAD. The widely used SPECT MPI agents, ^99mTc sestamibi and ^99mTc tetrofosmin, exhibit less than ideal pharmacokinetic properties with decreasing uptake with higher flows. ¹²³I has a similar energy as ^99mTc, an ideal half life, and is readily available from cyclotrons. The objective of this study was to develop an ¹²³I labeled MPI agent based on rotenone, a mitochondrial complex I inhibitor, as an alternative to currently available SPECT MPI agents. Methods: ¹²³I-CMICE-013 was synthesized by radiolabeling rotenone with ¹²³I in trifluoroacetic acid (TFA) with iodogen as the oxidizing agent at 60 °C for 45 min, followed by RP-HPLC purification. The product was formulated in 5% EtOH in 10 mM NaOAc pH 6.5. The inactive analog ¹²⁷I-CMICE-013 was isolated and characterized by NMR and mass spectrometry, and the structure determined. Micro-SPECT imaging studies were carried out in normal and infarcted rats. Biodistribution studies were performed in normal rats at 2 h (n = 6) and 24 h (n = 8) post injection (p.i.). Results: ¹²³I-CMICE-013 was isolated with >95% radiochemical purity and high specific activity (14.8–111 GBq/μmol; 400–3000 mCi/μmol). Structural analysis showed that rotenone was iodinated at 7′-position, with removal of the 6′,7′-double bond, and addition of a hydroxy group at 6′-position. MicroSPECT images in normal rats demonstrated homogeneous and sustained myocardial uptake with minimal interference from lung and liver. Absent myocardial perfusion was clearly identified in rats with permanent left coronary artery ligation and ischemia-reperfusion injury. In vivo biodistribution studies in normal rats at 2 h p.i. showed significant myocardial uptake (2.01 ± 0.48%ID/g) and high heart to liver (2.98 ± 0.93), heart to lung (4.11 ± 1.04) and heart to blood (8.37 ± 3.97) ratios. At 24 h p.i., the majority of ¹²³I-CMICE-013 was cleared from tissues, and a significant amount of tracer was found in the thyroid, indicating in vivo deiodination of the tracer. Conclusion: ¹²³I-CMICE-013 is a promising new radiotracer for SPECT MPI with high myocardial uptake, very good target to background ratios and favorable biodistribution characteristics.     

Antimycobacterial activity evaluation,time-kill kinetic and 3D-QSAR study of C-(3-aminomethyl-cyclohexyl)-methylamine derivatives

A series of C-(3-aminomethyl-cyclohexyl)-methylamine derivatives were synthesized and evaluated for their antitubercular activity. Some of the compounds exhibited potent activity against Mycobacterium tuberculosis H37Rv. One of the compound having t-butyl at para position of the benzene ring showed excellent activity even better than the standard drug ethambutol with MIC value 1.1 ± 0.2 μM. The time-kill kinetics study of two most active compounds showed rapid killing of the M. tuberculosis within 4 days. Additionally atom-based quantitative structure–activity relationship (QSAR) model was developed that gave a statistically satisfying result (R²) = 0.92, Q² = 0.75, Pearson-R = 0.96 and effectively predicts the anti-tuberculosis activity of training and test set compounds.