An efficient 2-aminothiazolesalicylaldehyde Fluorescent Chemosensor for Fe2+ ion Detection and Potential Inhibitor of NUDT5 Signaling Hormone for Breast Cancer Cell and Molecular Keypad Lock Application

A novel thiazole phenol conjugate 2-aminothiazolesalicylaldehyde (receptor1) was designed and synthesized for the first time through a single step process via schiff base condensation reaction. The formation of receptor1 was confirmed by FTIR, 13C NMR and 1H NMR. The receptor1 complexing with various metal ions studied through fluorescence spectroscopy showed its selectivity towards Fe2+ ion following a reverse photo induced electron transfer (PET) process compared to all other potentially competing ions. Furthermore, the receptor1 showed excellent reversibility property on adding EDTA solution. The binding affinity between receptor1-Fe2+ ion was found to be Ka = 2.22x102 M-1 and the sensing affinity of receptor1 towards Fe2+ ion at nanolevel concentration was 33.7x10-9 M which is lower than the detection limit of existing Schiff base. The receptor1 was used to detect Fe2+ ion in different water samples. Using molecular docking the chelating function of ligand (receptor1) was assessed as a potential inhibitor of NUDT5, a silence hormone signaling for breast cancer. The excellent reversibility property is used to construct INHIBIT molecular logic gate.

In silico studies of bacterial derived fatty acid as a potential inhibitor of 1FGE and 1BQO

Thrombomodulin (TM) and matrix metalloproteinase (MMPs) are the major factors that are responsible for lung cancer. Hence, the identification of novel compounds inhibiting TM and MMPs is the challenging task for the scientists. Even though synthetic drugs were developed, their toxicity and offtarget limit their usage. The current study aims to investigate the molecular simulations for bacterial derived stearic acid to estimate the in silico anticancer activity against TM and MMPs protein as target compounds and the findings were correlated with the standard drug vorinostat. Using Lamarckian genetic algorithm, the TM and MMPs were energy minimized and docked with stearic acid and vorinostat using auto dock 4.2 and visualized in PyMol software. Protein and ligand binding analysis revealed that stearic acid interacts with the amino acids of MMPs residues of PHE83, SER212, ALA213 and ASN214. It interacts with the TMs with two amino acid residues i.e. CYS407 and GLU408. Hence, compared to vorinostat, stearic acid shows a higher binding affinity towards MMPs and slightly lower affinity towards TM proteinase. We conclude that the computational analysis of ligand binding interaction of stearic acid suggests that it could be a potential inhibitor of matrix metallo proteinase and is effective against thrombomodulin and can be considered as an anticancer agent by in vivo studies.

In silico Identification of Potential Inhibitor Targeting Streptococcus mutans and Lactobacillus Acidophilus for the Treatment of Dental Caries

Background: Dental caries is one of the most common chronic diseases, and it is caused by the acid fermentation of bacteria that have become attached to the teeth. Streptococcus mutans (S. mutans) and Lactobacillus acidophilus (L. acidophilus) anchor surface proteins to the cell wall and form a biofilm to aid adhesion to the tooth surface. Some natural plant products, particularly several flavonoids, are effective inhibitors. However, given the scarcity of inhibitors and the emergence of drug resistance, the development of new inhibitors is critical. The high-throughput virtual screening approach was used in this study to identify new potential inhibitor of against S. mutans and L. acidophilus by using ligand (Ellagic acid). Aim: To evaluate the drug interaction ligand (Ellagic acid) and protein [A3VP1 of AgI/II] of Streptococcus mutans (PDB ID: 3IPK), glucan-1,6 - alpha-glucosidase from Lactobacillus acidophilus NCFM (PDB ID: 4AIE). Materials and Methodology: The pdb format of two selected proteins was retrieved from the RCSB protein database. Then inhibitors were docked with protein (A3VP1 of AgI/II) and glucan-1,6-alpha-glucosidase to identify the potent inhibitor. An evaluation criterion was based on the binding affinities by using AutoDock. Results: The binding energy of Ellagic acid - Streptococcus mutans docked complex-10.63 kcal/mol and with Ellagic acid – Lactobacillus acidophilus docked complex was -7.30 kcal/mol. Conclusion: In this study, Showed that lesser binding energy better is the binding of the ligand and protein. These findings can provide a new strategy for dental caries disease therapy by using Ellagic acid as a inhibitor against Streptococcus mutans and Lactobacillus acidophilus

The effects of Pinus brutia bark extract on pure and mixed continuous cultures of rumen bacteria and archaea, and fermentation characteristics in vitro

The aim of the study was to investigate the effects of Pinus brutia bark extract, which is rich in polyphenolic compounds of tannins, on both pure and mixed continuous cultures of rumen bacteria and archaea, as well as on rumen fermentation characteristics in vitro. Antimicrobial susceptibility assay with pure cultures was carried out in an anaerobic chamber. Pinus brutia bark extract exhibited a potential inhibitor activity (P<0.05) against pure cultures of Ruminococcus flavefaciens, Eubacterium ruminantium, and Methanobacterium formicicum while a growth stimulatory effect (P<0.05) was observed for Ruminoccocus albus, Butyrivibrio fibrisolvens, and Streptococcus bovis. Pinus brutia bark extract only had a potential inhibitor effect (P<0.05) on R. albus at the highest dose (1200 µg/mL). Pinus brutia bark extract also stimulated (P<0.05) the growth of pure cultures of Fibrobacter succinogenes, while it did not affect Megasphaera elsdenii, except at the highest dose. The effects of two doses (75 and 375 mg/L) of P. brutia bark extract on in vitro mixed cultures and rumen fermentation parameters were determined by the rumen simulation technique (Rusitec). Supplementation with P. brutia bark extract led to a quadratic decrease (P<0.05) in the cell numbers of R. flavefaciens. Production of total and individual short chain fatty acids (SCFA), acetate to propionate ratio (C2/C3), total protozoa, ruminal pH, and dry matter digestibility (DMD) did not change in the presence of P. brutia bark extract. Supplementation with both doses of P. brutia bark extract decreased (P<0.05) the ammonia-N concentrations. Ammonia-N concentration was lowest in the high-supplemented group (P<0.05). As a conclusion, inhibitory effects of P. brutia bark extract on some species in the pure cultures were in the same direction as with mixed ruminal cultures, while stimulatory effects disappeared. The lack of inhibitory effects on protozoa and on a large number of Gram-positive rumen bacteria in the mixed cultures suggests that its mechanism of action is not exactly similar to antibiotics. Although P. brutia bark extract did not alter ruminal SCFA, it could have potential to improve ruminal protein utilization without depressing rumen microbial fermentation.