Objective: TG2 is multifunctional protein. The up regulation leads into different pathological disorders. The objective of the present study was the prediction of a structural feature of TG2 (Tissue transglutaminase) protein with in silico approach.
Methods:In this study, we have investigated the structural feature of TG2 by using various biological databases (uniprot, NCBI, Pfam) and online tools such as BLAST, PDBsum, protoparam tools.
Results:The predicted structure of TG2 protein has shown that amino acid residues conserved throughout the sequence in selected mammals. During the course of evolution, mammalian TG2 protein is orthologus; human TG2 shares its characters with chimpanzee while mice and rat were closely related to each other. This protein was mainly cytosolic but also present in other cell organalles. It has four catalytic domains and three active sites with multiple metal binding domain specifically for calcium. The pI value was 5.11, GRAVY-0.283. The phosphorylation sites were present at serine and threonine. The structure was a monomer with 14 alpha helices and 9 sheets. Ramachandran plot showed about 98% residues in the favoured region.
Conclusion:Collectively, these data suggest that the predicted TG2 protein may act as a good therapeutic target. Targeting phosphorylation sites may help in down regulation of TG2. The modelled protein can be used for further work.
Aim:
Screening and development of TG2 inhibitors as anti lung cancer agent.
Background: Transglutaminase 2 (TG2) is multifunctional and ubiquitously expressed protein from transglutaminase family. It takes part in various cellular processes and plays an important role in the pathogenesis of autoimmune, neurodegerative and also cancer.
Background:
Transglutaminase 2 (TG2) is multifunctional and ubiquitously expressed protein from transglutaminase family. It takes part in various cellular processes and plays an important role in the pathogenesis of autoimmune, neurodegerative and also cancer.
Objective :
The of proposed study is to focused on screening of potent inhibitors of TG2 by in-silico method and synthesis its derivative as well as analysis of its activity by invitro approach.
Material and Methods:
Molecular docking studies have been carried on the different classes of TG2 inhibitors against the target protein. Nearly thirty TG2 inhibitors were selected from literature and docking was performed against transglutaminase 2. The computational ADME property screening was also carried out to check their pharmacokinetic properties. The compounds which exhibited positive ADME properties with good interaction with possessing least binding energy were further validated for their anti-lung cancer inhibition property against A549 cell lines by cytotoxicity studies.
Results:
The results of present study indicate that the docked complex formed by cystamine showed better binding affinity towards target protein so, this derivative of cystamine is formed using 2,5 dihydrobenzoic acid. Invitro results revealed that both molecule proved good cytotoxic agent against A549 lung cancer (875.10, 553.22 µg/ml) respectively. Further its activity should be validated on TG2 expressing lung cancer.
Conclusion :
Cystamine and its derivative can be act as potential therapeutic target for lung cancer but further its activity should be validated on TG2 expressing lung cancer.
Objective: The phytochemical analysis of Terminalia chebula, Terminalia bellirica, Phyllanthus emblica fruit extract as well as to evaluate the potential synergistic activity of screened plant extracts for anti-oxidant, anti-inflammatory and anti-cancer activity on MCF-7 breast cancer cell line. Methodology: In present study phytochemical constituent from selected plant material was extracted in different solvents. Antioxidant activity was evaluated by DPPH and FRAP assay against standard antioxidant. MTT assay was performed to find out cytotoxic and anti-inflammatory effect on MCF- breast cancer cell line. Result: Phytochemical analysis of the performed which showed that alkaloids, phenols, flavonoids and saponins. In context of antioxidant assays almost selected extracts showed moderate activity but ethanol extract of Terminalia chebula, proven to be having significant antioxidant activity over all extracts. Anti-inflammatory activity of MCF-7 breast cancer cell line exhibited that good activity with IC50 value 228.82µg/ml. Whereas Methanol extract of Terminalia bellirica and Aqueous extract of Phyllanthus emblica shown 432.45µg and 259.02µg respectively. Conclusion: The present study concludes that in among three tested extracts, Ethanol extract of Terminalia chebula exhibited prominent anticancer activity against Breast cancer (MCF-7) with significant IC50 value 228.82 µg. However further studies are needed to find out the structural of bioactive compounds and investigate mechanisms of antioxidant and anticancer activities of the bioactive compounds in in-vivo animal study.
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