Naseem Ahmed

Assessment of Human Biodistribution and Dosimetry of 4-Fluoro-11β-Methoxy-16α-18F-Fluoroestradiol Using Serial Whole-Body PET/CT

4-Fluoro-11β-methoxy-16α-18F-fluoroestradiol (4FMFES) is a newly developed radiolabeled estradiol analog for PET imaging of estrogen receptors (ERs) that shows improved target-to-background ratios, compared with 16α-18F-fluoroestradiol (FES), in small-animal models. The aim of this study was to assess the biodistribution, dosimetry, and safety of 4FMFES in healthy women. Methods: Ten healthy subjects (6 pre- and 4 postmenopausal women) who had fasted were injected with 66–201 MBq of 4FMFES at a high effective specific activity (median, 251 GBq/μmol). During a 2-h period, each subject underwent 4 serial rapid PET acquisitions and 2 low-dose CT acquisitions on a PET/CT camera. Volumes of interest were drawn over source organs for each PET acquisition, allowing the calculation of time–activity curves, residence times, and radiation dosimetry estimates. Serial blood samples were obtained to measure blood and plasma activity clearance. 4FMFES safety was assessed by blood and urine analyses and vital-sign monitoring. Results: A 4FMFES injection was well tolerated in all subjects. The liver showed high uptake, and the hepatobiliary excretion was massive. Little urinary excretion occurred. Uterus uptake was visualized in all subjects and remained relatively constant over time (maximum and mean standardized uptake values at 60 min were 5.34 ± 3.32 and 2.68 ± 1.89, respectively). Background activity was low and decreased over time, resulting in an increasing uterus-to-background ratio (12.1 ± 2.2 at 60 min). The critical organ was the gallbladder (0.80 ± 0.51 mGy/MBq), followed by the upper large intestine (0.13 ± 0.04 mGy/MBq), small intestine (0.12 ± 0.04 mGy/MBq), and liver (0095 ± 0.019 mGy/MBq). For a typical 4FMFES dose of 185 MBq, the effective dose was calculated at 4.82 ± 0.70 mSv. Conclusion: 4FMFES is considered safe for use in humans, and its effective dose remains well within acceptable limits. The absorbed dose to the gallbladder was relatively high and could potentially be reduced by injecting 4FMFES in patients who had not fasted. 4FMFES showed a significant, potentially estrogen receptor–mediated uterus uptake in both pre- and postmenopausal subjects.

Study on effects of temperature, moisture and pH in degradation and degradation kinetics of aldrin, endosulfan, lindane pesticides during full-scale continuous rotary drum composting

Study focused on effects of temperature, moisture and pH on degradation and degradation kinetics of aldrin, endosulfan (α), endosulfan (β) and lindane during vegetable waste composting using full-scale continuous rotary drum composter (FSCRDC). Extraction, concentration and quantification of pesticides were made from waste material at different stages by ultra-sonification, silica gel column and GC-MS analysis. Removal efficiency of aldrin, endosulfan α, endosulfan β and lindane was found 85.67%, 84.95%, 83.20% and 81.36% respectively due to optimum temperature, moisture, pH and enhanced microbial activity. Maximum temperature in inlet zone was found 60-65°C which is most suitable for complex microbial population. After feeding and turning in inlet zone, temperature reduced to 38°C from 60 to 65°C and regained it within 7-8h, and pH reduced to 5.3±0.2 from 7.5±0.3 in 4h and regained it in 10h. Heterotrophic bacteria Bacillus sp., Pseudomonas sp. and Lactobacillus sp. also decreased from 4.4×10(3) to 7.80×10(2)CFU g(-1) in 2 h due to gradual variation in temperature and pH. No significant temperature change was found in middle and outlet zones during feeding and turning. Degradation of pesticides was observed as first order kinetics and half-life of aldrin, endosulfan α, endosulfan β and lindane was reduced to 25.54, 18.43, 18.43 and 27.43 d from 1095, 60, 270 and 160 d respectively. Thus, the observations in contrast of removal and degradation kinetics of organochlorine pesticides residues in vegetable waste though full-scale rotary drum composting proved it the best suited technique.

Microbial diversity during Rotary Drum and Windrow Pile composting.

This study investigates the prevailing microbial communities during the composting of vegetable waste, cattle manure and saw dust, in a household (250 l) batch scale Rotary Drum composter and Windrow Pile. Physico‐chemical parameters were analyzed to study the organic matter transformations. Total organic matter reduced from 63.8% to 36.2% in rotary drum and 39.6% in windrow pile composting. The C/N ratio decreased from 26.52 to 8.89 and 14.33 in rotary drum and windrow pile composting. The indigenous population of total heterotrophic bacteria decreased in rotary drum and windrow pile composting after 20 days. However, total fungal load initially increased within initial 4 days, then subsequently reduced in final composts. The average number of fecal coliforms and fecal Streptococci showed decrement with time, in both composting systems. Escherichia coli and Salmonella species number deduced during the study. Composting cycle started with Gram positive rods but ended up with the dominance of Gram negative bacilli shaped bacteria. Transformation of organic compounds during the biodegradation of organic waste, difference in the utilization of nutrients (organic matter) by the different group of microbes and high temperature could be cited as a possible reason of the above changes. Scanning electron microscopy has been used to obtain the surface structures of the cultured mycoflora. Results of the study revealed that higher diversity of microbes prevailed in rotary drum as compared to windrow pile, yielding more stable and pathogenic free compost in lesser period of composting. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

Design, synthesis and antiproliferative activity of functionalized flavone-triazole-tetrahydropyran conjugates against human cancer cell lines.

Under optimized reaction conditions, an efficient synthetic method has been developed to afford the functionalized flavone-triazole-tetrahydropyran conjugates via click reactions. The Cu-catalyzed 1,3-dipolar cycloaddition reaction gave the pure products, 5-iodo- and 5-H-1-(tetrahydropyran)-1,2,3-triazol-4-(3-methoxylflavone) derivatives in excellent yield (90-98%) within 1-3 h. Further, Pd-catalyzed Suzuki coupling of 5-iodo-1,2,3-triazoles with phenylboronic acids afforded 5-phenyl-1-(tetrahydropyran)-1,2,3-triazol-4-(3-methoxylflavone) derivatives in excellent yield (93-95%) in 4-5 h. Products (3a-l, 4a-j) were screened in vitro for their anti-proliferative activity against three human cancer cell lines (MDA-MB 231, KCL22 and Hela). Compounds 3c, 3g, 3i, 3j, 4c and 4h have shown better cytotoxicity (IC50 0.61-1.68 μM) than the reference drugs. Compounds 4e (IC50 0.70 μM), 3j (IC50 0.61 μM) and 4d (IC50 0.65 μM) exhibited anti-proliferative activity better than the reference drugs against the MDA-MB 231 cells, KCL22 cells and HeLa cells respectively.

Efficient Route to Highly Functionalized Chalcone-Based Pyranocoumarins via Iodine-Promoted Michael Addition Followed by Cyclization of 4-Hydroxycoumarins

Abstract Molecular iodine is used as an efficient promoter in the regioselective synthesis of highly functionalized chalcone-based pyranocoumarin derivatives using 4-hydroxycoumarin in acetic acid solvent at 100 °C. Under optimized reaction conditions, our protocol (Michael addition followed by intermolecular cyclization) has tolerance for many functional groups and gave products in good to excellent yields (75–98%) within 1–2 h. [Supplementary materials are available for this article. Go to the publishers online edition of Synthetic Communications® for the following free supplemental resource: Full experimental and spectral details.] GRAPHICAL ABSTRACT

A facile approach for the synthesis of novel 1-oxa- and 1-aza-flavonyl-4-methyl-1H-benzo[d][1,3]oxazin-2(4H)-ones by microwave enhanced Suzuki–Miyaura coupling using bidentate chromen-4-one-based Pd(II)–diimine complex as catalyst

A facile access to diversely substituted 1-oxa- and 1-aza-flavonyl-4-methyl-1H-benzo[d][1,3]oxazin-2(4H)-ones using the microwave assisted phosphine-free Suzuki coupling of bromo flavones with boronic acids using a chromen-4-one-containing Pd(II)–diimine complex (C) as catalyst under aerobic conditions is reported. A small amount of the catalyst (0.3 mol%) was found to be highly effective for coupling to form the products in very high yields in 18–20 min under mild reaction conditions. This catalytic system is compatible with a broad spectrum of olefinic or aryl bromide and aryl- or heteroaryl-boronic acids. After screening various catalytic conditions, it was found that a Pd complex of the bidentate Schiff base ligand was able to efficiently catalyze these reactions with yields up to 95%. The effect of solvent, base and catalyst loading on the coupling reaction is also described.

Synthesis of flavonoids based novel tetrahydropyran conjugates (Prins products) and their antiproliferative activity against human cancer cell lines

Following our previously reported Prins cyclization strategy, a series of novel and highly functionalized flavonoid based THPs (Prins products) were designed, synthesized and evaluated for their antiproliferative activity. Novel products were afforded in excellent yields (72-96%) within 20-90 min at 62 °C using flavonoid aldehydes, homoallylic alcohols, p-TSA·H2O (catalyst and reagent) and MS 4 Å in CHCl3. Deprotection of tosyl group was achieved with TFA (catalyst and solvent) at 140 °C to obtain 4-hydroxytetrahydropyrans and further reaction of 4-hydroxytetrahydropyrans with cinnamoyl chloride afforded 4-cinnamate tetrahydropyrans under neat condition. Synthesized compounds evaluated against human cancer cell lines (Hep3β, MCF-7 and Hela), have shown moderate to good antiproliferative activity in vivo. Compounds 3q and 3zb exhibited similar cytotoxicity (IC50 6.6 ± 1.4, 6.9 ± 1.0 μM, respectively) to the reference drug doxorubicin (IC50 7.6 ± 0.9 μM) against the MCF-7 cancer cell line. Compound 3zb was found equally active as the standard drug (IC50 4.48 ± 2.1 μM) against the Hep3β cell line and compounds 3c and 3q showed moderate cytotoxicity (IC50 10.40 ± 1.1, 12.9 ± 1.7 μM, respectively) against the HeLa cell line.

Characterization of high rate composting of vegetable market waste using Fourier transform-infrared (FT-IR) and thermal studies in three different seasons

Fourier transform-infrared (FT-IR), Thermogravimetry (TG), Differential thermal analyses (DTA) and Differential Thermogravimetric (DTG) studies of a mixture of vegetable waste, saw dust, tree leaves and cow dung for microbial activity (feedstock) and their compost were reported in three different seasons i.e. winter, spring and summer. The correlation between spectral studies and compost composition provide information regarding their stability and maturity during composting. FT-IR spectra were conferred the functional groups and their intensity and TG, DTG and DTA for wt. loss, rate of wt. loss and enthalpy change in compost. Weight loss in feedstock and compost at two different temperatures 250–350 and 350–500°C was found 38.06, 28.15% for inlet and 14.08, 25.67% for outlet zones in summer and 50.59, 29.76% for inlet and 18.08, 25.67% in outlet zones in spring season, higher (5–10%) than winter. The corresponding temperatures in DTA in the samples from inlet to outlet zone were; endotherm (100–200°C), due to dehydration, exotherm (300–320°C), due to peptidic structure loss and exotherm (449–474°C) due to the loss of polynuclear aromatic structures, which were higher by 4°C and 10–20°C and rate of wt. loss was higher by 5–10% in spring and summer season, respectively than winter season composting, reported regardless of the maturation age of the compost. Relative intensity of exotherms (300–320/449–474°C) gave the thermally more stable fractions of organic compound. Our results indicated that the rotary drum composting of organic matters in spring and summer season gave higher molecular complexity and stability than the winter season.

β-Cyclodextrin/IBX in water: highly facile biomimetic one pot deprotection of THP/MOM/Ac/Ts ethers and concomitant oxidative cleavage of chalcone epoxides and oxidative dehydrogenation of alcohols

A mild and efficient one-pot deprotection of THP/MOM/Ac/Ts ethers, and concomitant oxidative cleavage of epoxides and oxidative dehydrogenation of alcohols to form β-hydroxy 1,2-diketones, 1,2,3-triketones and conjugated aromatic carbonyl systems (chalcones) using β-cyclodextrin/IBX in water has been developed. o-Iodoxybenzoic acid, a readily available hypervalent iodine(V) reagent, was found to be highly effective with β-cyclodextrin in carrying out the deprotection and subsequent transformations under an eco-friendly environment. The reaction gave moderate to excellent yields ranging from 50–99% at 60 °C in 40 min to 6 h.

β-Cyclodextrin in water: highly facile biomimetic one pot deprotection of phenolic THP/MOM/Ac/Ts ethers and concomitant regioselective cyclization of chalcone epoxides and 2′-aminochalcones

A mild and efficient one-pot deprotection of THP/MOM/Ac/Ts ethers and the concomitant cyclization of chalcone epoxides to 2-hydroxyindanones or 2′-aminochalcones to aza-flavanones using β-cyclodextrin in water has been developed. β-CD was found to be highly effective at carrying out the deprotection and sequential transformations in an eco-friendly environment affording moderate to excellent yields (59–99%) at 60 °C in 8–22 min. Water, an eco-friendly reaction medium, has been utilized for the first time in this reaction. The merits of the presented protocol include the high yields and catalyst reusability and the protocol precludes the use of metals and organic solvents. The present method is much milder but more advanced than those reported earlier.