Leukemia is one of the most common forms of cancer worldwide, particularly in children. Multidrug-resistant leukemia remains a significant challenge in cancer therapy due to resistance mechanisms, including drug efflux pumps. Apoptosis, particularly via caspase-3 activation, is a key target to overcome this resistance. This study aims to explore and assess the mechanisms of flavonoids CPD5, CPD7, and doxorubicin as potential agents against multidrug-resistant leukemia. Key molecular targets identified include JNK1, AKT1, MAPK3, TP53, NFKB1, and CREB1, linked to apoptosis signaling. Molecular docking with the caspase-3 structure (PDB ID: 4JJE) reveals that CPD5 and doxorubicin exhibit more stable binding energies and better localization within the protein 4JJE compared to CPD7. Molecular dynamics simulation over 100 ns confirms stable binding interactions for all compounds. In silico ADMET predictions have assessed oral bioavailability, showing CPD7 meets all pharmacokinetic criteria, being non-toxic, with superior distribution capacity and high absorption. These findings suggest CPD7 as a promising future drug for treating multidrug-resistant leukemia by inducing apoptosis through caspase-3 activation.
Aryl azides are 'green' reagents and provide a fascinating area of chemistry and have many uses in industry as pharmaceutical agents. Azidothymidine (AZT) is used to treat HIV-AIDS and a 2-dimethylaminoethyl azide (DMAZ) is a powerful explosive. The 'click' reaction based on these has been awarded the coveted Nobel Prize in 2022. 'Click' reaction is a 'green' regiospecific reaction since atom efficiency is very high as no atom loss occurs. Reactions of azides involve many unusual and fascinating transition states and intermediates. In this paper, is discussed the photochemistry of 'Azidometa-Meconine'. Photolysis at 5 degrees C using wavelength of 254 nm for 6 h has been carried out. The reaction product is subjected to preparative Thin Layer Chromatography (TLC), two bands namely an 'Upper band' and a 'Lower band' have been separated, molecular weight values in LC-MS spectrum differs from each other by six atomic mass units (six hydrogens). One part of the reactive intermediate underwent addition of hydrogen (reduction) and other dehydrogenation (oxidation) which thus constitutes a rare example of dimerization of nitrene intermediate previously unknown in the literature. Detailed LC-MS studies have provided evidence for the formation of two products with yield around 94.99%, which is an unusually high yield for such photochemical reactions. Further, spectroscopic studies (UV-Visible, FT-IR, 1H NMR, etc.) have also been carried out for corroborating the successful formation of these two products.
This research focuses on the synthesis, characterization, computational studies and in vitro antibacterial studies of pyrazolone phenylhydrazone and its transition metal complexes of copper and manganese. Pyrazolone p-Flurophenylhydrazone has been synthesized and characterized using FT-IR, 1H NMR and mass spectrometry. In the same way pyrazolone Cu (II) and Mn (II) transition metal complexes have been synthesized and characterized using FT-IR, ESI mass spectrometry, UV-Visible spectrometry and powder X-ray diffraction (XRD). In addition to these, Quantum mechanical Density Functional Theorycalculations have been simulated for ligand and metal complexes in order to obtain the electronic and structural properties and reactivity of the molecules. Furthermore, molecular docking studies have been carried out on Cu and Mn metal complexes with E. coli zinc deformylase inhibitor protein to access the interaction and binding of molecule with respect to the target site of receptor and compared with standard drugs Penicillin-G and Ampicillin. The antibacterial efficiency of ligand and its metal complexes have been evaluated against Gram-Positive and Gram-Negative bacterial assays to investigate its antimicrobial potential. These findings aid in the discovery of new successful leads with potential antimicrobial properties that can be optimized in future to get an effective drug candidates.
A new compound, 2-amino-4-(4-bromophenyl)-6-(phenylamino)pyridine-3,5-dicarbonitrile, has been synthesized by the catalyst-free reaction of 2-(4-bromobenzylidene)malononitrile with malononitrile and benzylamine. The structure of the reaction product has been determined by NMR spectroscopy and X-ray diffraction analysis. A probable reaction mechanism and intramolecular rearrangement has been proposed.
Using the methods of physicochemical analysis (DTA, X-ray diffraction, MSA, as well as density and microhardness measurements), phase formation in the InSe-SrSe system has been studied and its phase diagram constructed. It is found that the InSe-SrSe system is a quasi-binary section of the ternary system Sr-In-Se and is eutectic. A ternary compound of the formula SrInSe2 is formed in the system with a component ratio of 1:1. The SrInSe(2 )compound melts congruently at 1180 degrees C. According to the results of X-ray structural analysis, it is established that the SrInSe2 compound crystallizes in the orthorhombic syngony, the lattice parameters are: a = 10.95 & Aring;; b = 8.65 & Aring;; c = 8.42 & Aring;. The coordinates and temperatures of the two eutectics formed in the system are 15 and 65 mol % SrSe and t = 847 K and t = 1273 K, respectively. In the system at room temperature based on the InSe compound, solid solutions reach up to 5 mol % SrSe, and on it is SrSe up to 3 mol % InSe. As a result of studying the electrical conductivity (sigma), thermal conductivity (alpha), current (I) and specific resistance (rho) of solid solution alloys (InSe)(1-x)(SrSe)(x) (x=0.01; 0.02; 0.03; 0.05), it has been established that solid solution alloys are semiconductors with medium resistance.
