Leveraging the catalytic machinery of LSD1 (KDM1A), a series of covalent styrenylcyclopropane LSD1 inhibitors were identified. These inhibitors represent a new class of mechanism-based inhibitors that target and covalently label the FAD cofactor of LSD1. The series was rapidly progressed to potent biochemical and cellular LSD1 inhibitors with good physical properties. This effort resulted in the identification of 34, a highly potent (<4 nM biochemical, 2 nM cell, and 1 nM GI50), and selective LSD1 inhibitor. In-depth kinetic profiling of 34 confirmed its covalent mechanism of action, validated the styrenylcyclopropane as an FAD-directed warhead, and demonstrated that the potency of this inhibitor is driven by improved non-covalent binding (K I). 34 demonstrated robust cell-killing activity in a panel of AML cell lines and robust antitumor activity in a Kasumi-1 xenograft model of AML when dosed orally at 1.5 mg/kg once daily.

Meiotic recombination between homologous chromosomes is promoted by the collaborative action of two RecA homologs, Rad51 and meiosis-specific Dmc1. The filament assembly of Dmc1 is promoted by meiosis-specific Mei5-Sae3 in budding yeast. Mei5-Sae3 shows sequence similarity to fission yeast Sfr1-Swi5, which stimulates DNA strand exchanges by Rad51 as well as Dmc1. Sae3 and Swi5 share a conserved motif with the amino acid sequence YNEI/LK/RD. In this study, we analyzed the role of the YNEL residues in the Sae3 sequence in meiotic recombination and found that these residues are critical for Sae3 function in Dmc1 assembly. L59 substitution in the Sae3 protein disrupts complex formation with Mei5, while Y56 and N57 substitutions do not. These observations reveal the differential contribution of conserved YNEL residues to Sae3 activities in meiotic recombination.

Mangrove ecosystem are known for their diverse and rich microbiota. Here human influence is limited, so novelty in bacterial diversity is more common as mangroves ecosystem comes under conservative area and human interference in restricted here. In this present study, mangrove sample like mangrove associated Soil, Coastal water, Roots were collected from Borivali coastal area of manori creek and Jhow Island, Maharashtra under prior permission from CCF, Mangrove Cell, Maharashtra government. Halophiles are in demand in many Biotech based company and their enzymes are equally in demand due their properties. Here in the present experiment, with the help of enriched media 30 samples were processed from which 8 samples were from Jhow Island and 22 samples from borivali coastal-line. All the samples were screened with 10% salt and 20% salt concentration (NaCl). Sample were also screened for 7 pH and 9 pH growth parameters from Borivali and Jhow Island respectively. From above mention samples, total 62 Isolates were obtained, which were screened for Bio-Industrially important enzymes like Amylase, Protease and Cellulase. These enzymes have great demand when they are active in high salt concentration or alkaline pH. These enzymes may emphasize more Scientific-Entrepreneur in India.

Objective: To develop and characterize ginger oil loaded solid lipid nanoparticles (SLN) for enhancement of its stability. Methods: Ginger oil loaded SLNs were prepared in four different batches by double emulsification method using different concentrations of soya lecithin and Tween 80. Further, these batches were characterized for particle size, zeta potential, drug entrapment efficiency and in vitro release study. After observing the results, batch F4 was further characterized by Fourier Transform Infrared Spectroscopy (FTIR), Transmission Electron Spectroscopy (TEM) and Differential Scanning Calorimetry (DSC). In addition the optimized batch was subjected to anti-microbial study. Finally, stability studies were done by storing the F4 formulation at accelerated condition, room temperature, refrigerated temperature and photostability were performed by exposing the formulation to UV/fluorescence lamp for 6 mo. Results: The encapsulation efficiency of various batches of SLNs was in the range of 79.75 to 90.24%. The size ranges varied between 50 to 1000 nm. Zeta potential of all formulations was found to be in the range of-44.52 to-49.37 mV. The FTIR spectra of optimized F4 batch indicated no significant structural changes or complexation reactions between drug and excipients. Moreover, TEM image of displayed spherical shape with smooth surface. In vitro drug release study exhibited 95% drug release up to 12 h which indicated suitability of formulation. Thus F4 batch formulation stored at room temperature and refrigerated conditions was found most stable while, accelerated and photostability samples were found to be most susceptible in comparison. Conclusion: The physicochemical stability of ginger oil extract was enhanced by loading it into solid lipid nanocarriers; the resulting SLNs also showed good antimicrobial potential against Klebsiella pneumonia throughout storage conditions.

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