Molecular Docking of Nimbolide Extracted from Leaves of Azadirachta indica with Protein Targets to Confirm the Antifungal, Antibacterial and Insecticidal Activity.

Nimbolide, a tetranortriterpenoid (limonoid) compound isolated from the leaves of Azadirachta indica, was screened both in vitro and in silico for its antimicrobial activity against Fusarium oxysporum f. sp. cubense, Macrophomina phaseolina, Pythium aphanidermatum, Xanthomonas oryzae pv. oryzae, and insecticidal activity against Plutella xylostella. Nimbolide exhibited a concentration-dependent, broad spectrum of antimicrobial and insecticidal activity. P. aphanidermatum (82.77%) was more highly inhibited than F. oxysporum f. sp. cubense (64.46%) and M. phaseolina (43.33%). The bacterium X. oryzae pv. oryzae forms an inhibition zone of about 20.20 mm, and P. xylostella showed about 66.66% mortality against nimbolide. The affinity of nimbolide for different protein targets in bacteria, fungi, and insects was validated by in silico approaches. The 3D structure of chosen protein molecules was built by homology modelling in the SWISS-MODEL server, and molecular docking was performed with the SwissDock server. Docking of homology-modelled protein structures shows most of the chosen target proteins have a higher affinity for the furan ring of nimbolide. Additionally, the stability of the best-docked protein-ligand complex was confirmed using molecular dynamic simulation. Thus, the present in vitro and in silico studies confirm the bioactivity of nimbolide and provide a strong basis for the formulation of nimbolide-based biological pesticides. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01104-6.

Numerical estimation of calibration matrices for 241Am measurements using HPGe based in-vivo monitoring system.

In-vivo measurements of 241Am using HPGe detectors become complicated when the active adjacent source organs interfere with the target organ measurements. It is important to calculate the contribution of confounding organs to estimate the activity of the target organ accurately. In the current study, numerical simulations were performed using FLUKA Monte Carlo code and International Commission on Radiological Protection (ICRP) computational reference phantoms to determine the calibration matrices consisting of the calibration and cross-talk coefficients for three interfering organs namely, lungs, liver and skeleton. It was found that the interference from adjacent organs contaminated with 241Am was found to be significant in the case of lungs and liver. Knee monitoring was least influenced by the activity possessed by other source organs due to their anatomical distance from the knee. A comparison between lung and liver coefficients obtained from the Lawrence Livermore National Laboratory (LLNL) torso phantom and thorax phantom derived from ICRP adult male voxel phantom was performed. It was found that variations in coefficients obtained from simulations and experiments range between 2% and 48%. The differences were attributed to the uncertainties arising from the composition of the phantoms and detectors, size and shape of organs, positional errors, and source distribution. A comparison of calibration matrices of adult male and adult female thorax voxel phantoms revealed that all the coefficients except knee as the target organ were larger for the female thorax phantom owing to the lesser bulk of attenuating tissues on its chest. The coefficients obtained from simulations for different phantoms also showed that the organ activity estimation can be significantly affected by the subject morphology.

Anticancer Potential of Hydroxychavicol Derived from Piper betle L: An in Silico and Cytotoxicity Study.

Piper betle L. is a popular medicinal plant in Asia, and extracts of the plant leaf are used for several therapeutics. It is known for its rich source of phenolic compounds, including hydroxychavicol. Hydroxychavicol is an allylbenzene that has gained much attention due to its anticancer properties. The current study quantified and purified hydroxychavicol from P. betle L. and predicted its anticancer competence through in silico and cytotoxicity studies. Leaf samples of 22 P. betle L. accessions from different locations of Tamil Nadu, India, were analyzed using reverse phase-high performance liquid chromatography for quantification of hydroxychavicol. The highest quantity of hydroxychavicol was obtained from the accession BV22 (89.2%). Chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of hydroxychavicol using SwissADME satisfied the physicochemical property guidelines of Lipinski's Rule of Five, ensuring its drug-likeness behavior. Molecular docking studies confirmed the interaction of hydroxychavicol with all 16 tested cancer targets. In Vitro MTT assay of hydroxychavicol in bone cancer cell lines (MG63) also demonstrated the anticancer competency, indicating the requirement to formulate the molecule as a drug in treating various types of cancers.

Determination of calibration matrix for HPGe-based in vivo monitoring system for estimation of 241Am in lungs and liver.

The detection of internal contamination may be carried out by direct or indirect methods. The lung counting technique using an array of High Purity Germanium (HPGe) detectors is one of such direct detection methods. It is known from the literature that the estimation of activity by organ counting can lead to erroneous results if an amount of activity is possessed by an adjacent organ. In the case of HPGe-based lung monitoring, the estimation could be misleading if the activity is possessed by the liver, which is a proximal organ. In such cases the measured activity should be modified using cross-talk coefficients which account for the contribution from adjacent organs. The determination of cross-talk coefficients for 241Am was carried out by placing the detectors over inactive lungs of an Lawrence Livermore National Laboratory phantom when the source activity was contained in the liver and vice versa. A calibration matrix was formulated with calibration coefficients as diagonal elements and cross-talk coefficients as off-diagonal elements. The measured activities may be modified by matrix multiplication with the inverse of the calibration matrix to nullify the contribution from adjacent organs. The current work has empirically determined the fitting equations which relate calibration and cross-talk coefficients for lungs and liver measurement geometries with muscle-equivalent chest wall thickness (MEQ-CWT) values. The values of these coefficients were determined for an average MEQ-CWT of 1.77 cm for lungs and 1.33 cm for liver. The calculations showed that the activity contribution from liver to lungs was 29% higher than that of lungs to liver. A verification exercise was conducted to demonstrate this method. For the given calibration source, the percent overestimation was reduced for lung activity, while the liver activity was slightly underestimated. In the case of old exposure follow-up monitoring cases, the 241Am activity built up in liver could interfere with the lung monitoring results and this method using the calibration matrix may be used for estimation of more accurate results.

Nanofibrous matrixes with biologically active hydroxybenzophenazine pyrazolone compound for cancer theranostics.

The nanomaterial with the novel biologically active compounds has been actively investigated for application in cancer research. Substantial use of nanofibrous scaffold for cancer research with potentially bioactive compounds through electrospinning has not been fully explored. Here, we describe the series of fabrication of nanofibrous scaffold loaded with novel potential biologically active hydroxybenzo[a]phenazine pyrazol-5(4H)-one derivatives were designed, synthesized by a simple one-pot, two step four component condensation based on Michael type addition reaction of lawsone, benzene-1,2-diamine, aromatic aldehydes and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one as the substrates. The heterogeneous solid state catalyst (Fe (III) Y-Zeolite) could effectively catalyze the reaction to obtain the product with high yield and short reaction time. The synthesized compounds (5a-5p) were analyzed by NMR, FTIR and HRMS analysis. Compound 5c was confirmed by single crystal XRD studies. All the compounds were biologically evaluated for their potential inhibitory effect on anticancer (MCF-7, Hep-2) and microbial (MRSA, MTCC 201 and FRCA) activities. Among the compounds 5i exhibited the highest levels of inhibitory activity against both MCF-7, Hep-2 cell lines. Furthermore, the compound 5i (BPP) was evaluated for DNA fragmentation, flow cytometry studies and cytotoxicity against MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. In addition, molecular docking (PDB ID: 1T46) studies were performed to predict the binding affinity of ligand with receptor. Moreover, the synthesized BPP compound was loaded in to the PHB-PCL nanofibrous scaffold to check the cytotoxicity against the MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. The in vitro apoptotic potential of the PHB-PCL-BPP nanofibrous scaffold was assessed against MCF-7, Hep-2 cancerous cells and fibroblast cells at 12, 24 and 48h respectively. The nanofibrous scaffold with BPP can induce apoptosis and also suppress the proliferation of cancerous cells. We anticipate that our results can provide better potential research in nanomaterial based cancer research.

Concentration of natural radionuclides in raw water and packaged drinking water and the effect of water treatment.

The raw water (RW) samples collected from natural sources are subjected to water treatment process, including reverse osmosis (RO), and are packed in bottles as packaged drinking water (PDW). Raw water (21 samples) taken from deep wells of Chennai and Secunderabad which are used in the production of PDW, were analysed for (234)U, (235)U, (238)U, (226)Ra, (228)Ra and (210)Pb activity concentrations. Activity Concentrations of (234)U, (235)U, (238)U, (226)Ra, (228)Ra, (210)Pb and (210)Po in PDW were also analysed. The mean activity concentrations of (234)U, (235)U, (238)U, (226)Ra, (228)Ra and (210)Pb in RW at Chennai were 12.1, ≤1.3, 7.1, 2.6, 27.5, and 16.3 mBq/L respectively. The mean activity concentrations of (234)U, (235)U, (238)U, (226)Ra, (228)Ra and (210)Pb in RW at Secunderabad were found to be 40.9, 1.7, 41.5 84.5, 100.1, and 17.0 mBq/L respectively. The mean concentrations of (234)U, (235)U, (238)U, (226)Ra, (228)Ra, (210)Pb and (210)Po in PDW at Chennai were found to be ≤1.3, ≤1.3, ≤1.3, ≤0.2, ≤1.7, 28.0 and 1.2 mBq/L at Secunderabad were found to be ≤1.3, ≤1.3, 1.7, 4.3, 5.0 and 28.1 mBq/L. The study indicated a considerable reduction in the concentration of natural radionuclides due to water treatment. The reduction ratios of RW to PDW for (234)U, (238)U, (226)Ra, (228)Ra were 97, 96, 94 and 95%. In case of (210)Pb, the PDW showed higher concentration of (210)Pb than RW. This was due to its in growth from (222)Rn which was not removed in the RO process.

Evaluation of 25 y of environmental monitoring data around Madras Atomic Power Station (MAPS), Kalpakkam, India.

The Environmental Survey Laboratory at Kalpakkam, India carries out elaborate monitoring programme involving atmospheric, terrestrial and aquatic samples for radioactivity to evaluate the impact of operating two pressurised heavy water reactors. This paper presents the evaluation of 25 y (1983-2008) data. Statistical analysis of the environmental data for different radionuclides showed that the data best fits log-normal distribution. The data analysed showed that fission products such as (137)Cs, (90)Sr and (131)I were due to global fallout only. A ratio of 0.2 was obtained for (90)Sr to (137)Cs in air filter samples, only during Chernobyl accident period. The transfer factor of (137)Cs and (90)Sr for rice was computed to be 0.23 and 0.03 and vegetables 0.25 and 0.10, respectively. Activation products (3)H and (41)Ar are the only radionuclides that are related to MAPS operation. A strong correlation (r = 0.9) was observed between (3)H activity in air and (3)H discharged to the atmosphere. A similar correlation (r = 0.8) was observed in (3)H concentration in seawater and (3)H discharged in the liquid waste. The annual internal dose due to (3)H and annual external dose due to (41)Ar evaluated in the last 25 y show that the members of the public received less than 2 % of the dose limit (1 mSv y(-1)) set by ICRP 72.

Insect antifeedant and growth regulating activities of salannobutyrolactone and desacetylsalannobutyrolactone.

Salannobutyrolactone and its deacetylderivative were tested for insect antifeedant and growth regulatory activities against the tobacco cutworm, Spodoptera litura. Salannobutyrolactone was the most effective antifeedant. Desacetylsalannobutyrolactone increased larval duration and larval mortality.