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131.
Shradha Bahuguna Manish Kumar Gajanand Sharma Rajendra Kumar Bhupinder Singh Kaisar Raza 《AAPS PharmSciTech》2018,19(3):1084-1092
Derivatization of fullerenes to polyhydroxylated fullerenes, i.e., fullerenols (FLU), dramatically decreases their toxicity and has been reported to enhance the solubility as well as cellular permeability. In this paper, we report synthesis of FLU as nanocarrier and subsequent chemical conjugation of Methotrexate (MTX) to FLU with a serum-stable and intracellularly hydrolysable ester bond between FLU and MTX. The conjugate was characterized for physiochemical attributes, micromeritics, drug-loading, and drug-release and evaluated for cancer cell-toxicity, cellular-uptake, hemocompatibility, protein binding, and pharmacokinetics. The developed hemocompatible FL-MTX offered lower protein binding vis-à-vis naïve drug and substantially higher drug loading. The conjugate offered pH-dependent release of 38.20?±?1.19% at systemic pH and 85.67?±?3.39% at the cancer cell pH. FLU-MTX-treated cells showed significant reduction in IC50 value vis-à-vis the cells treated with pure MTX. Analogously, the results from confocal scanning laser microscopy also confirmed the easy access of the dye-tagged FLU-MTX conjugate to the cell interiors. In pharmacokinetics, the AUC of MTX was enhanced by approx. 6.15 times and plasma half-life was enhanced by 2.45 times, after parenteral administration of single equivalent dose in rodents. FLU-MTX offered enhanced availability of drug to the biological system, meanwhile improved the cancer-cell cytotoxicity, sustained the effective plasma drug concentrations, and offered substantial compatibility to erythrocytes. 相似文献
132.
Singh Rajendra Pandey Deepak Devi Neena Chand Duni 《Bioprocess and biosystems engineering》2018,41(8):1225-1232
Bioprocess and Biosystems Engineering - Butyramide is a commodity chemical having wide range of applications from material science to biological sciences including synthesis of therapeutic drugs,... 相似文献
133.
The recent advancement in new generation fluorinated pyrethroids (e.g., transfluthrin, metofluthrin etc.), the use of semi-volatile vapour phase insecticides for control of mosquitoes and other domestic pests rises. Enabling the examination of the vapour toxicity profiles of these molecules and many other similar new generation molecules will provide new avenues for researchers for understanding the bio-potency in the spatial killing of pests. Hence, it is critical to establish a well-controlled portable vapour-phase bioassay method that can provide the desired precision, accuracy, linearity and robustness. In this respect, we have designed a vapour-toxicity apparatus comprising glass assemblies and developed a novel bioassay method. We found that KT50 and percentage knockdown at 60?min reflect the concentration dependency. This validates and confirms that the method is sensitive enough to distinguish between concentrations and suitable for concentration-response experiments. We found that KT50 and percentage knockdown at 60?min at a given concentration does not differ significantly between experiments. Hence, the method has repeatability and precision. Percentage mortality and total KT50 against Culex quinquefasciatus shows that percentage mortality increases and KT50 decreases linearly with the increasing concentration. This method provides an easy to operate tool to test the vapour toxicity profiles of any vapour phase insecticide molecules against mosquitoes and flying insects. 相似文献
134.
Marion Rother Erik Gonzalez Ana Rita Teixeira da Costa Lea Wask Isabella Gravenstein Matteo Pardo Matthias Pietzke Rajendra Kumar Gurumurthy Jörg Angermann Robert Laudeley Silke Glage Michael Meyer Cindrilla Chumduri Stefan Kempa Klaus Dinkel Anke Unger Bert Klebl Andreas Klos Thomas F. Meyer 《Cell host & microbe》2018,23(5):661-671.e8
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Method for Restricting Incorporation of Radioactivity from 3H-Thymidine into Deoxyribonucleic Acid Only During Outgrowth of Spores of Bacillus cereus T 总被引:8,自引:5,他引:3
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When heat-activated spores of Bacillus cereus T (thy(-)) were germinated and grown in medium containing (3)H-thymidine, a significant amount of radioactivity was incorporated into ribonucleic acid and deoxyribonucleic acid (DNA). A method was developed to restrict the incorporation of radioactivity from (3)H-thymidine into DNA only. This was accomplished by labeling the cells with (3)H-thymidine in the presence of 2 mg of 2-deoxyadenosine per ml, 250 mug each of uracil, cytosine, and guanosine per ml, and 500 mug of adenosine per ml. Under these conditions, 97% of the radioactivity incorporated into cold trichloroacetic acid-insoluble material was associated with DNA only. In the absence of these compounds, DNA contained only 72% of the total radioactivity incorporated into cold acid-insoluble material. 相似文献
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Haque A Rai V Bahal BS Shukla S Lattif AA Mukhopadhyay G Prasad R 《Biochemical and biophysical research communications》2007,352(2):491-497
Candida drug resistance protein (Cdr1p) is a major drug efflux protein, which plays a key role in commonly encountered clinical azole resistance in Candida albicans. We have analyzed its sequence in several azole resistant clinical isolates to evaluate the allelic variation within CDR1 gene and to relate it to its functional activity. The sequence analysis revealed 53 single nucleotide polymorphisms (SNPs), out of which six were non-synonymous single nucleotide polymorphisms (NS-SNPs) implying a change in amino acid and were found in two or more than two allelic combinations in different sensitive or resistant isolates. We have identified three new NS-SNPs namely, E948P, T950S, and F1399Y, in isolates wherein F1399Y appeared to be unique and was present in one of the naturally occurring azole resistant isolates obtained from Indian diabetic patients. However, site-directed mutagenesis showed that the residue F1399 in between TMS 11 and TMS 12 does not affect the functionality of Cdr1p. Taken together, our SNPs analyses reveal that unlike human P-gp, the naturally acquired allelic variations are mostly present in non-conserved regions of the protein which do not allow Cdr1p to genetically evolve in a manner, that would allow a change in its functionality to affect substrate recognition, specificity, and drug efflux activity of C. albicans cells. 相似文献
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