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31.
Mithun Rudrapal Dipak Chetia Vineeta Singh 《Journal of enzyme inhibition and medicinal chemistry》2017,32(1):1159-1173
Among three series of 1,2,4-trioxane derivatives, five compounds showed good in vitro antimalarial activity, three compounds of which exhibited better activity against P. falciparum resistant (RKL9) strain than the sensitive (3D7) one. Two best compounds were one from aryl series and the other from heteroaryl series with IC50 values of 1.24 µM and 1.24 µM and 1.06 µM and 1.17 µM, against sensitive and resistant strains, respectively. Further, trioxane derivatives exhibited good binding affinity for the P. falciparum cysteine protease falcipain 2 receptor (PDB id: 3BPF) with well defined drug-like and pharmacokinetic properties based on Lipinski’s rule of five with additional physicochemical and ADMET parameters. In view of having antimalarial potential, 1,2,4-trioxane derivative(s) reported herein may be useful as novel antimalarial lead(s) in the discovery and development of future antimalarial drug candidates as P. falciparum falcipain 2 inhibitors against resistant malaria. 相似文献
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Samrin Shaikh Varsha Shriram Tushar Khare Vinay Kumar 《Physiology and Molecular Biology of Plants》2020,26(3):593-604
In an attempt to find an alternative and potent source of diosgenin, a steroidal saponin in great demand for its pharmaceutical importance, Helicteres isora suspension cultures were explored for diosgenin extraction. The effect of biotic elicitors on the biosynthesis of diosgenin, in suspension cultures of H. isora was studied. Bacterial as well as fungal elicitors such as Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae and Aspergillus niger were applied at varying concentrations to investigate their effects on diosgenin content. The HPLC based quantification of the treated samples proved that amongst the biotic elicitors, E. coli (1.5%) proved best with a 9.1-fold increase in diosgenin content over respective control cultures. Further, the scaling-up of the suspension culture to shake-flask and ultimately to bioreactor level were carried out for production of diosgenin. During all the scaling-up stages, diosgenin yield obtained was in the range between 7.91 and 8.64 mg l−1, where diosgenin content was increased with volume of the medium. The quantitative real-time PCR (qRT-PCR) analysis showed biotic elicitors induced the expression levels of regulatory genes in diosgenin biosynthetic pathway, the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and cycloartenol synthase (CAS), which can be positively correlated with elicited diosgenin contents in those cultures. The study holds significance as H. isora represents a cleaner and easy source of diosgenin where unlike other traditional sources, it is not admixed with other steroidal saponins, and the scaled-up levels of diosgenin achieved herein have the potential to be explored commercially. 相似文献
34.
Shrivastava Vineeta Savarimuthu Arockiasamy Patil Manoj Sarkar Purbasha Hadole Sainath Dasgupta Santanu 《Plant Cell, Tissue and Organ Culture》2021,144(2):359-370
Plant Cell, Tissue and Organ Culture (PCTOC) - Jatropha curcas is an undomesticated crop and its plantations did not meet commercial expectation due to absence of high yielding commercial line with... 相似文献
35.
Andrei Fokine Baldeep Khare Yingyuan Sun Michael G. Rossmann 《Journal of structural biology》2019,205(3):53-58
The interpretation of cryo-electron tomograms of macromolecular complexes can be difficult because of the large amount of noise and because of the missing wedge effect. Here it is shown how the presence of rotational symmetry in a sample can be utilized to enhance the quality of a tomographic analysis. The orientation of symmetry axes in a sub-tomogram can be determined using a locked self-rotation function. Given this knowledge, the sub-tomogram density can then be averaged to improve its interpretability. Sub-tomograms of the icosahedral bacteriophage phiX174 are used to demonstrate the procedure. 相似文献
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We investigated the role of cuticular lipids, body melanisation and body size in conferring contrasting levels of desiccation
resistance in latitudinal populations of Drosophila melanogaster and Drosophila ananassae on the Indian subcontinent. Contrary to the well known role of cuticular lipids in water proofing in diverse insect taxa,
there is lack of geographical variations in the amount of cuticular lipids per fly in both the species. In D. ananassae, quite low levels of body melanisation are correlated with lower desiccation resistance. By contrast, increased levels of
desiccation resistance are correlated with quite high melanisation in D. melanogaster. Thus, species specific cuticular melanisation patterns are significantly correlated with varying levels of desiccation resistance
within as well as between populations and across species. Role of body melanisation in desiccation resistance is further supported
by the fact that assorted dark and light flies differ significantly in cuticular water loss, hemolymph and dehydration tolerance.
However, similar patterns of body size variation do not account for contrasting levels of desiccation resistance in these
two Drosophila species. Climatic selection is evidenced by multiple regression analysis with seasonal amplitude of thermal and humidity
changes (Tcv and RHcv) along latitude on the Indian subcontinent. Finally, the contrasting levels of species specific distribution
patterns are negatively correlated with RHcv of sites of origin of populations i.e. a steeper negative slope for D. ananassae corresponds with its desiccation sensitivity as compared with D. melanogaster. Thus, evolutionary changes in body melanisation impact desiccation resistance potential as well as distribution patterns
of these two Drosophila species on the Indian subcontinent. 相似文献
39.
Cu, Zn superoxide dismutase (SOD1) has been implicated in the familial form of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). It has been suggested that mutant mediated SOD1 misfolding/aggregation is an integral part of the pathology of ALS. We study the folding thermodynamics and kinetics of SOD1 using a hybrid molecular dynamics approach. We reproduce the experimentally observed SOD1 folding thermodynamics and find that the residues which contribute the most to SOD1 thermal stability are also crucial for apparent two-state folding kinetics. Surprisingly, we find that these residues are located on the surface of the protein and not in the hydrophobic core. Mutations in some of the identified residues are found in patients with the disease. We argue that the identified residues may play an important role in aggregation. To further characterize the folding of SOD1, we study the role of cysteine residues in folding and find that non-native disulfide bond formation may significantly alter SOD1 folding dynamics and aggregation propensity. 相似文献
40.
N. K. Arora Ekta Khare S. Singh D. K. Maheshwari 《World journal of microbiology & biotechnology》2010,26(5):811-816
Most of the legume crops are affected by metal stress present in the soil mainly due to contaminated agrochemicals and sewage sludge. The effect of aluminium, and heavy metals copper, iron and molybdenum on growth and activity of enzymes of fast and slow growing rhizobial sps. was studied. Sinorhizobium meliloti RMP5 was found to be more tolerant to metal stress than Bradyrhizobium BMP1. Both the strains were extremely sensitive to Al than other metals. Al was much more deleterious for the enzymatic activities (nitrate reduction, nitrite reduction, nitrogenase and uptake hydrogenase) of strain RMP5 and BMP1. Cu showed inhibitory effect on growth and enzyme activities of Bradyrhizobium strain at all concentrations. However, in S. meliloti RMP5 all the tested enzymatic activities increased up to the concentration of 0.1 mM Cu. Fe enhanced the growth and enzyme activities of S. meliloti RMP5 and Bradyrhizobium BMP1 up to 100 mM concentration. Mo enhanced all the tested enzymatic activities of S. meliloti RMP5 up to 1 mM. Nitrate and nitrite reduction activities of Bradyrhizobium BMP1 increased up to 1 mM concentration. However, nitrogenase and hydrogenase activities of Bradyrhizobium BMP1 got enhanced only up to 0.5 mM Mo. Both Fe and Mo are the key components of the enzyme nitrogenase and nitrate reductase and enhanced the growth and enzyme activities of both the sps. The study of physiology of nitrogen fixing ability of both fast and slow growing rhizobial strains reported that the supplementation of Mo and Fe in soils along with the biological formulations will enhance the process of symbiotic nitrogen fixation. 相似文献