Insight of Tp53 Mutations and their effect on Protein in Different Feline and Canine Neoplasms

Background: Mutations in the Tp53 gene, a tumor suppressor gene, may cause dysfunction in growing cells and hinder the phenomenon of apoptosis, an alleged cause of tumorigenesis. It is involved in conservation of the genome and DNA repair, mutations of this gene may cause the damaged cells to grow continuously.Methods: The type of molecular changes in Tp53 gene and their effects on physiochemical and structural properties of this protein in various Canine and Feline cancers were observed in this study by using online bioinformatics tools.Results: Our results indicated that lymphomas and perianal adenocarcinomas (PAC) have the same mutation at c. 104, while mammary tumors and canine transmissible venereal tumor (CTVT) contain different mutations. Referring to changes in protein, synonymous mutations in granulomas were observed while certain mutations in squamous cell carcinoma (SCC) and head & neck tumors were detected in Canis familiaris. In Felis catus, the mutant protein was similar to wild type protein with exception of mutant 5 of mammary tumor, which had a deletion at the 287 amino acid position.Conclusion: The insight gathered on the p53 mutant proteins in both species aided our understanding of the in-vivo fate of the p53 protein and its isoforms and the effects that morphological changes can have on the fate of cells. Furthermore, isolation of this protein may augment our understanding about the structural biology of these proteins

Tyrosinase inhibition: conformational analysis based studies on molecular dynamics calculations of bipiperidine based inhibitors.

Two series of variably N-substituted biperidines were synthesized by condensing various acid chlorides, alkyl halides and anhydrides with 1,4-bipiperidine. The new compounds were tested as tyrosinase inhibitors and a structure-activity relationship (SAR) study was carried out. Potent inhibition was observed in the case of the 4'-methylbenzyl substitution on this atom (IC50 = 1.72 microM) with this compound being a lead for future drug design. Additionally, calculations of the important QSAR molecular descriptors were done on the biperidine analogues after their 2 ps molecular dynamics (MD) simulations using molecular mechanics force field (MMFF) approaches. Using MD simulations potential and total energies were calculated for the energy minimized models of bipiperidine and the most active analogs 2, 3, 4, 6, 8 and 10

Data from: Synthesis of 4-substituted ethers of Benzophenone and their antileishmanial activity

Leishmaniasis is a vector born protozoan disease, it is mainly originated by the bite of sand fly and initiated when parasite is transmitted to human at the stage of metacyclic flagellated promastigote form. In current study, a synthesis of a series of 4-substituted benzophenone ethers 1-20 has been carried out in good yields and their in vitro antileishmanial activity has also been performed. Among synthetic derivatives, fifteen compounds 1, 3, 5-12, 15, and 17-20 showed antilieshmanial activity against promastigotes of Leishmania major with IC50 values in the range of 1.19 - 82.30 µg/mL, and compared with the standard pentamidine (IC50 = 5.09 ± 0.09 µg/mL). This study identified a series of new antileishmanial molecules as potential lead. Structures of these synthetic compounds were deduced by different spectroscopic techniques such as 1H-NMR, 13C-NMR, EI-MS, HREI-MS, and IR

Phenoxyacetohydrazide Schiff Bases: β-Glucuronidase Inhibitors

Phenoxyacetohydrazide Schiff base analogs 1–28 have been synthesized and their in vitro β-glucouoronidase inhibition potential studied. Compounds 1 (IC50 = 9.20 ± 0.32 µM), 5 (IC50 = 9.47 ± 0.16 µM), 7 (IC50 = 14.7 ± 0.19 µM), 8 (IC50 = 15.4 ± 1.56 µM), 11 (IC50 = 19.6 ± 0.62 µM), 12 (IC50 = 30.7 ± 1.49 µM), 15 (IC50 = 12.0 ± 0.16 µM), 21 (IC50 = 13.7 ± 0.40 µM) and 22 (IC50 = 22.0 ± 0.14 µM) showed promising β-glucuronidase inhibition activity, better than the standard (D-saccharic acid-1,4-lactone, IC50 = 48.4 ± 1.25 µM)

Synthesis of 2-Aminopyrimidine Derivatives and Their Evaluation as β-Glucuronidase Inhibitors: In Vitro and In Silico Studies

Currently the discovery and development of potent β-glucuronidase inhibitors is an active area of research due to the observation that increased activity of this enzyme is associated with many pathological conditions, such as colon cancer, renal diseases, and infections of the urinary tract. In this study, twenty-seven 2-aminopyrimidine derivatives 1–27 were synthesized by fusion of 2-amino-4,6-dichloropyrimidine with a variety of amines in the presence of triethylamine without using any solvent and catalyst, in good to excellent yields. All synthesized compounds were characterized by EI-MS, HREI-MS and NMR spectroscopy. Compounds 1–27 were then evaluated for their β-glucuronidase inhibitory activity, and among them, compound 24 (IC50 = 2.8 ± 0.10 µM) showed an activity much superior to standard D-saccharic acid 1,4-lactone (IC50 = 45.75 ± 2.16 µM). To predict the binding mode of the substrate and β-glucuronidase, in silico study was performed. Conclusively, this study has identified a potent β-glucuronidase inhibitor that deserves to be further studied for the development of pharmaceutical products

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