3D-QSAR-based design, synthesis and biological evaluation of 2,4-disubstituted quinoline derivatives as antimalarial agents.

2,4-Disubstituted quinoline derivatives were designed based on a 3D-QSAR study, synthesized and evaluated for antimalarial activity. A large dataset of 178 quinoline derivatives was used to perform a 3D-QSAR study using CoMFA and CoMSIA models. PLS analysis provided statistically validated results for CoMFA (r2ncv = 0.969, q2 = 0.677, r2cv = 0.682) and CoMSIA (r2ncv = 0.962, q2 = 0.741, r2cv = 0.683) models. Two series of a total of 40 2,4-disubstituted quinoline derivatives were designed with amide (quinoline-4-carboxamide) and secondary amine (4-aminoquinoline) linkers at the -C4 position of the quinoline ring. For the purpose of selecting better compounds for synthesis with good pEC50 values, activity prediction was carried out using CoMFA and CoMSIA models. Finally, a total of 10 2,4-disubstituted quinoline derivatives were synthesized, and screened for their antimalarial activity based on the reduction of parasitaemia. Compound #5 with amide linker and compound #19 with secondary amine linkers at the -C4 position of the quinoline ring showed maximum reductions of 64% and 57%, respectively, in the level of parasitaemia. In vivo screening assay confirmed and validated the findings of the 3D-QSAR study for the design of quinoline derivatives.

Estimation of critical conditions of polymers based on monitoring the polymer recovery.

Liquid chromatography at critical conditions (LCCC) is a very attractive chromatographic technique on the border between the size exclusion and liquid adsorption mode of the liquid chromatography. The strong interest in LCCC arises from the fact that it is well suited to analyze the block lengths in segmented copolymers or the heterogeneities with regard to end groups present, for example, in functionalized polymers e.g., telechelics. In this paper a new method for identification of the critical conditions of synthetic polymers is proposed, which requires only one polymer sample with higher molar mass. The method is based on monitoring the recovery of the polymer sample from a column. The composition of the mobile phase is modified until the polymer sample is fully recovered from the column. The corresponding composition of the mobile phase is composition corresponding to LCCC. This new method was applied for the determination of critical conditions for polyethylene, syndiotactic polypropylene and isotactic polypropylene. The results of the new method will be compared to those of classical approaches and advantages will be pointed out.

Monte Carlo calculations for efficiency calibration of a whole-body monitor using BOMAB phantoms of different sizes.

Internal contamination due to high-energy photon (HEP) emitters is assessed using a scanning bed whole-body monitor housed in a steel room at the Bhabha Atomic Research Centre (BARC). The monitor consists of a (203 mm diameter × 102 mm thickness) NaI(Tl) detector and is calibrated using a Reference BOMAB phantom representative of an average Indian radiation worker. However, a series of different size physical phantoms are required to account for size variability in workers, which is both expensive and time consuming. Therefore, a theoretical approach based on Monte Carlo techniques has been employed to calibrate the system in scanning geometry with BOMAB phantoms of different sizes characterised by their weight (W) and height (H) for several radionuclides of interest ((131)I, (137)Cs, (60)Co and (40)K). A computer program developed for this purpose generates the detector response and the detection efficiencies (DEs) for the BARC Reference phantom (63 kg/168 cm), ICRP Reference male phantom (70 kg/170 cm) and several of its scaled versions. The results obtained for different size phantoms indicated a decreasing trend of DEs with the increase in W/H values of the phantoms. The computed DEs for uniform distribution of (137)Cs in BOMAB phantom varied from 3.52 × 10(-3) to 2.88 × 10(-3) counts per photon as the W/H values increased from 0.26 to 0.50. The theoretical results obtained for the BARC Reference phantom have been verified with experimental measurements. The Monte Carlo results from this study will be useful for in vivo assessment of HEP emitters in radiation workers of different physiques.

Selected organ dose conversion coefficients for external photons calculated using ICRP adult voxel phantoms and Monte Carlo code FLUKA.

The adult reference male and female computational voxel phantoms recommended by ICRP are adapted into the Monte Carlo transport code FLUKA. The FLUKA code is then utilised for computation of dose conversion coefficients (DCCs) expressed in absorbed dose per air kerma free-in-air for colon, lungs, stomach wall, breast, gonads, urinary bladder, oesophagus, liver and thyroid due to a broad parallel beam of mono-energetic photons impinging in anterior-posterior and posterior-anterior directions in the energy range of 15 keV-10 MeV. The computed DCCs of colon, lungs, stomach wall and breast are found to be in good agreement with the results published in ICRP publication 110. The present work thus validates the use of FLUKA code in computation of organ DCCs for photons using ICRP adult voxel phantoms. Further, the DCCs for gonads, urinary bladder, oesophagus, liver and thyroid are evaluated and compared with results published in ICRP 74 in the above-mentioned energy range and geometries. Significant differences in DCCs are observed for breast, testis and thyroid above 1 MeV, and for most of the organs at energies below 60 keV in comparison with the results published in ICRP 74. The DCCs of female voxel phantom were found to be higher in comparison with male phantom for almost all organs in both the geometries.

Monte-Carlo simulation of uncertainty in the estimation of 125I in the thyroid.

At the Bhabha Atomic Research Centre, a thin (76 mm diameter x 2 mm thickness) NaI (Tl) detector is used for the assessment of (125)I in the thyroid of the radiation workers engaged in the preparation of radio-immunoassay kits. The detector was calibrated using a REMCAL (radiation equivalent manikin calibration) phantom with a known amount of the (125)I activity filled in its thyroidal cavity. Since (125)I emits low-energy photons ranging from 27 to 35.4 keV, its detection efficiency depends on several parameters such as neck-to-detector distance, detector size, unknown tissue thickness overlying (OTT) the thyroid and the shape and size of the thyroid. To account for uncertainties introduced by these factors in the estimation of (125)I, a computer program based on the Monte Carlo photon transport techniques was developed. The program simulates the detector response and the corresponding detection efficiencies using two thyroid models: (1) revised MIRD head phantom and (2) Ulanvosky model. The program has been validated with experimental measurements carried out using a REMCAL phantom. The computed values of uncertainties due to placement errors (+/-0.5 cm) for different detector sizes, differences in the OTT of the thyroid (0.6-2.0 cm) and different thyroid shapes are presented in this paper. The computed values of the calibration factors, determined for the revised MIRD phantom, varied from 5.23 to 1.06 x 10(-2) counts per photon for detector distance of 3-12 cm and from 7.53 to 3.66 x 10(-2) counts per photon for OTT varying from 0.6 to 2.0 cm keeping the detector at a distance of 3 cm. This study shows that the variations in OTT constitute a major source of uncertainty. The computed uncertainties due to various parameters should be taken into account while estimating the thyroidal burden of (125)I in the radiation workers. The feasibility of using coincidence method for absolute determination of the (125)I activity in the thyroid is also discussed in this paper.

Comparison of observed body retention of uranium in natural condition in an average Indian adult with the values predicted by the ICRP biokinetic model.

The daily intake of natural uranium and its contents in the lungs, skeleton, liver and kidney of an Indian adult population group was estimated using radiochemical neutron activation analysis (RNAA). These data on daily intake (through inhalation and ingestion) were used to compute the uranium contents in the lungs and other systemic organs such as the skeleton, liver and kidney, using the new human respiratory tract model (HRTM) and the new biokinetic model of uranium. The theoretically computed uranium contents in the lungs, skeleton, liver and kidney of an average Indian adult are 1.16, 1.96, 0.07 and 0.04 microg, respectively, and the corresponding experimentally measured values are 1.23 (1.76), 2.92 (2.5), 0.07 (1.76) and 0.19 (1.47) microg in an urban population group living in Mumbai. The values given in parentheses are geometric standard deviation (GSD). It is seen that the measured uranium contents in the lungs, skeleton and liver agree very well with the corresponding computed values, but the measured value for the kidney is observed to be on the higher side of the computed value. However, in view of many uncertainties, the overall agreement between the measured and the computed values can be considered to be good. Therefore, the result from this study can be taken as a validation of the new biokinetic model of uranium in Indian conditions.

Assessing skull burdens of actinides using a mathematical phantom: a Monte Carlo approach.

In vivo monitoring techniques are needed to estimate the amount of an actinide in the skeleton in addition to that in the lungs and liver. Skull counting with external detectors has been a standard procedure for this purpose. Realistic skull phantoms are normally used to calibrate the counting systems. However, the fabrication of realistic phantoms is extremely difficult and expensive. Therefore, a theoretical approach based on Monte Carlo methods in conjunction with a Cristy mathematical phantom has been examined for assessing skull burdens of actinides. A computer program that generates surface sources of actinides on the skull and simulates low-energy photon transport in the heterogeneous media of the head region of the Cristy phantom was developed for this purpose. The program determines the observable pulse height spectrum of the detector and the corresponding calibration factors for different counting geometries. The computer program was used to generate the pulse height spectra and the corresponding calibration factors of 20 cm and 15 cm diameter phoswich detectors, each positioned on the left and right sides and on the top of the head region of the Cristy phantom, whose skull surfaces were assumed to have a uniform distribution of 241Am. The computed calibration factor for a counting geometry consisting of three phoswich detectors (15 cm diameter each) surrounding the phantom's skull was found to be in excellent agreement with the experimental results obtained for the same geometry using a realistic physical skull phantom. This provided a validation of the realistic design of the skull in the Cristy phantom, implying that the results reported in this paper could be used for in vivo measurements of skull burdens of 241Am for the stated counting geometry.

A Monte Carlo approach to assessing 147Pm in the liver of the adult phantom.

A low-background phoswich detector is used to detect small amounts of 147Pm--a pure beta-emitting nuclide--present in the liver of an occupational worker. The assessment was based on the measurement of bremsstrahlung radiation produced by the beta particles in the tissue. Computer programs based on Monte Carlo techniques for photon transport have been developed to calculate the response of an external phoswich detector to 1) a 147Pm point source embedded in tissue-equivalent slabs of various thicknesses; and 2) various source distributions of 147Pm in the liver of an adult phantom. The goal is to theoretically calibrate the phoswich detector for each source distribution and to study the variation of maxima of the spectra with the depth of the source in the adult phantom liver and tissue-equivalent slabs. The initial bremsstrahlung photon distribution of 147Pm in water has been computed using Wyard's and Pratt's methods. These calculations have been compared with experimental measurements using Perspex acrylic sheet slabs. Good agreements have been noted when the initial bremsstrahlung spectrum is obtained by using Wyard's method. These results find applications in monitoring the liver burdens in occupational workers handling 147Pm-based radioluminous paints.