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.
A novel ligand, 2-[(1,3-benzothiazol -2-yl) amino] acetic acid (BAA), has been prepared by condensation reaction of 2-aminobenzothiazole with chloroacetic acid. BAA prepared ligand has been applied to prepare three different organotin carboxylate complexes via condensation reactions with a salt of corresponding organotin(IV) chloride. The synthesized ligand BAA and complexes have been systematically identified via the use of Fourier transform infrared spectroscopy (FTIR), multinuclear magnetic resonance spectroscopy (H-1 and Sn-119 NMR), and carbon (C), hydrogen (H) and nitrogen (N) elemental analysis, checking their fundamental integrity. BAA antioxidant ability and their organotin(IV) carboxylate complexes have been estimated via different established methods: CUPRAC (Cu ion Reducing Antioxidant Capacity) and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assays. Results point towards all organotin(IV) carboxylate complexes showing significantly larger inhibition percentages in contrast to free BAA ligand, underlining the serious role of the Tin(IV) centers in raising antioxidant ability. Particularly, the Ph3Sn(IV)COO-complex has demonstrated superior functioning by both methods, assigned to its noticeable steric and electronic properties resulting from the Ph-3 group substituents.
Gastric cancer, a highly aggressive malignancy, ranks fifth globally in new cases and deaths in 2022. Natural products from traditional Chinese medicine exhibit potential in cancer therapy. The present study investigates the mechanism of benzophenanthridine alkaloids from Macleaya microcarpa as potential anti-gastric cancer agents, targeting the NF-kappa Binducing kinase (NIK, protein ID: 4G3F). The results indicate that CPD1 likely modulates the non-canonical NF-kappa B pathway, with molecular docking revealing a superior binding energy (-9.86 kcal/mol) compared to IMD 0354 (-7.61 kcal/mol). Molecular dynamics simulations over 100 ns confirm stable interactions, with RMSD ranging from 0.20 to 0.25 nm, Rg around 2.1 nm, and SASA from 150 to 165 nm2, supporting a robust binding profile. In silico ADMET analysis demonstrates high intestinal absorption, limited distribution, CYP3A4 metabolism, and a good clearance rate, with no AMES toxicity. These results position CPD1 as a promising NIK inhibitor for gastric cancer therapy.
Gastric cancer ranks as the fifth leading cause of cancer globally, posing a significant challenge despite extensive research and funding efforts. Medicinal chemists continue to face difficulties in developing practical and durable therapies, particularly due to the heightened reliance of cancer cells on Glucose-6-Phosphate Dehydrogenase (G6PD)-mediated NADPH production compared to normal cells. This study investigates the pharmacokinetics and molecular targets of selected steroids as potential anti-gastric cancer agents. The results demonstrate that these steroids likely induce apoptosis by modulating key signalling pathways, with G6PD inhibition increasing reactive oxygen species and activating caspase-3, while regulating cell survival and proliferation through targets such as ATP1A1 and NOTCH1. Molecular docking analyses with the protein 7E6I reveal that CPD5 exhibits greater stability and better localisation within the 7E6I binding pocket than DHEA. Molecular dynamics simulations over 100 ns further confirm a consistent binding mode, highlighting CPD5's effective inhibition of the protein 7E6I. MMGBSA reveals binding free energies of -5.13 kcal/mol (CPD5-7E6I) versus - 14.38 kcal/mol (DHEA-7E6I). DFT highlights CPD5's reactivity exceeding DHEA's. ADMET profiling confirms CPD5's non-toxicity, stability, and high absorption. Thus, CPD5 represents a viable candidate for gastric cancer therapy via 7E6I inhibition.
Cobalt substituted copper chromite spinels (Cu1-xCoxCr2O4, where x = 0, 0.25, 0.5, 0.75 and 1.0) have been prepared by homogeneous co-precipitation method. The materials have been characterized in detail by X-ray diffraction, BET surface area, and FT-IR spectroscopy. Powder X-ray diffraction pattern reveals the spinel phase formation and energy dispersive X-ray analysis indicates the correct stoichiometry. Oxidative dehydrogenation of ethylbenzene to styrene is conducted with air as an oxidant. It is shown that the catalysts are highly active. Reusability studies of the catalysts show that cobalt substituted copper chromite spinels are stable under the reaction conditions.
Herein is reported the density functional theoretical study and DNA cleavage activity of an aminobenzoquinone, 2,5bis(cyclohexylamino)cyclohexa-2,5-diene-1,4-dione (BCBQ). Despite aminobenzoquinones being recognized for their biological activity, they remain relatively unexplored in theoretical studies. Single crystal X-ray analysis of BCBQ has already been reported. Detailed analysis of its structural parameters has elucidated the biological activity of such compounds, aiding the design of substituted ABQs for multiple uses.
Four series of aryl hydrazides have been synthesized using potassium hydrogen phthalate-assisted condensation by stirring aryl hydrazines with various substituted benzaldehydes and acetophenones at room temperature. The yield of this condensation is more than 85%. The influence of solvent on the yield has been studied. These hydrazides have been characterized by their physical constants, UV, IR, NMR, and mass spectral data. The characteristic spectral frequencies have been correlated with Hammett substituent constants and Swain Lupton's parameters using single and multi-regression analysis. From the statistical analysis results, the spectral quantitative structure-activity relationships have been assessed. The ligand-protein interaction ability of these hydrazines have been examined using molecular docking analysis.
Aiming for the synthesis of unreported molecular hybrids of 1,2,3,4-tetrahydropyrimidine and adamantane moiety containing nicotinoyl group in position 5 of the tetrahydropyrimidine ring suitable for use as anti-inflammatory agents, the precursor enaminones 3a-h have been reacted with 1-adamantanamine 4 and formaldehyde under thermal conditions producing the desired products 5a-h. The enaminone derivatives 3a-h are obtained by reacting formylated 3-acetylpyridine 2 with various primary amines. The structures of (3-((3s,5s,7s)-adamantan-1-yl)-1-aralkyl/aryl-1,2,3,4-tetrahydropyrimidin5-yl)(pyridin-3-yl)methanones 5a-h prepared in this investigation have been determined by various analytical and spectroscopic methods, in addition to the X-ray crystallographic analysis. The anti-inflammatory study of the synthesized compounds demonstrates promising activity.
Heterocyclylic derivatives of benzothiazole and pyrazole have been synthesized using both traditional and contemporary synthesis methods. The current study involves both conventional synthesis and catalyst-assisted techniques for the preparation of the desired organic compounds. Additionally, it includes the characterization of the synthesized compounds and a comparative analysis of traditional and modern methods in terms of reaction time, yield, and their applicability. A comprehensive overview of these compounds is presented, highlighting their chemical significance and potential applications in drug development. The central research question addresses the efficacy of synthesis methods and characterization techniques for these derivatives. This work not only contributes to the understanding of benzothiazole and pyrazole derivatives but also sheds light on their biological implications, aiming to pave the way for future research and application in pharmaceuticals.
New Schiff base chelates of Copper(II) derived from the Schiff base ligand ethylenediaminobi(chromone-3carbaldehyde) (FCED), viz., [Cu(FCED)Cl]Cl (1), [Cu(FCED)Br]Br (2), [Cu(FCED)(NO3)](NO3) (3) and [Cu(FCED)](ClO4)2 (4) have been synthesized and characterized. Microanalytical data, molar conductance and magnetic susceptibility values have been obtained and IR, UV-Visible, EPR spectral studies, TG/DTA, and DFT studies have been carried out to suggest the tentative structures of the complexes. The ligand acts as a neutral tetradentate ONNO donor ligand and the bonding sites are Nitrogen atoms of azomethine groups and Oxygen atoms of carbonyl groups. A square pyramidal geometry is suggested for complexes 1, 2 and 3 and a square planar geometry is suggested for 4. The crystal data indicate that the complex 3 crystallizes in monoclinic P21/n space group with a distorted square pyramidal structure and the it-it stacking interactions results in polymeric chains in unit cell of the complex.
A series of novel Cu (II) complexes have been produced using the conventional thermal method. The biologically active ligands (L) are created by refluxing a dicumarol derivative with aldehydes in ethanol. The Cu (II) compounds have been synthesized by mixing an aqueous solution of the metal in a 1:1 molar ratio with ethanolic ligands and modified ciprofloxacin. The structures of the ligands and their copper complexes have been analyzed and confirmed through elemental analysis, FT-IR, 1H and 13C NMR, and mass spectrometry. The thermal properties of the newly synthesized mixed-phase Cu (II) complexes have been investigated using thermo-gravimetric analysis. Both the ligands and their complexes have been screened for their in vitro inhibition, anti-tubercular, and antimicrobial activities, which show significantly higher potency compared to the parent ligands used for complexation.
Two Schiff bases viz. 2-(((2-(phenylamino)phenyl)imino)methyl)phenol ((LH)-H-1) and 2-methoxy-6-(((2-(phenylamino)phenyl)imino)methyl)phenol ((LH)-H-2) have been synthesized by the reaction of 2-aminodiphenylamine with salicylaldehyde and o-vanillin in 1:1 molar ratio. A series of transition metal complexes of Cr(II), Co(II) and Cu(II) have been synthesized using Schiff bases ((LH)-H-1) and ((LH)-H-2) in a 1:2 molar ratios. The newly synthesized ligands and metal complexes have been characterized by elemental analysis and different spectroscopic techniques including FT-IR, UV-Vis, NMR and mass spectrometry. The DFT method has been incorporated to get the electronic properties of ligands and their transition metal complexes. The spectroscopic analysis and computational method indicate distorted octahedral geometry around metal centers. The in vitro antimicrobial activities of synthesized ligands and transition metal complexes have been evaluated against Escherichia coli and Staphylococcus aureus. The results indicate that metal complexes exhibit higher antibacterial activity as compared to free Schiff bases and lower antibacterial activity as compared to the standard drug Gentamycin.
Copper (II) complexes (3a-d) with (16E)-2,6-dimethyl-N-(2-phenylquinoline-4(1H)-ylidene)-5-(phenylselanyl) pyrimidine-4-amine ligands have been developed. They have been characterised by elemental analysis and several spectroscopic studies. Absorption spectra, fluroscence investigations, and viscosity tests reveal how the copper complexes interact with the calf thymus (CT-DNA). Furthermore, the ligand's ability to inhibit acetylcholinesterase (AChE) has been studied in order to establish its efficacy in the treatment of neurodegenerative diseases. Compared to normal Rivastigmine and Galantamine, the synthesised ligand 2c shows selective inhibition (AChE and BuChE) with IC50 values of 0.18 and 3.03 mu M. A molecular docking study has been carried out.
A mixture of 5-chloro-1H-benzo[d]imidazole 1, K2CO3 and 2-bromoacetonitrile in DMF is stirred at 60 degrees C temperature for 8 h. to afford compound 2. A mixture of 2-(5-chloro-1H-benzo[d]imidazol-1-yl) acetonitrile, NH2OH.HCl and triethylamine in dry DCM is stirred at room temperature for 8 hr. The aromatic carboxylic acids and Vilsmeier reagent are added and resulting mixture stirred for further 7 h at same temperature to give the crude 1,2,4-oxadiazoles 4a-l. All the synthesised compounds have been screened for anti-bacterial evaluation. Among them 4f, 4g, and 4h are established to have more efficient bacterial inhibitory action against B. subtilis, with MICs of 3.12, 3.12, and 1.56 gg/mL, respectively, whereas typical streptomycin MICs are 6.25 gg/mL. Compound 4h has shown more potent activity against S. aureus, with MIC value of 3.12 gg/mL, whereas compound 4f has shown equipotent activity against the S. aureus, with MIC value of 6.25 gg/mL. Compound 4k has shown equipotent activity against B. subtilis and good activity against S. aureus with MIC values of 3.12 gg/mL and 6.25 gg/mL respectively.
A molecular hybridization strategy has been employed to synthesize 7[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]-3methyl-4-aryl-7H-isoxazolo[5,4-b]pyrazolo[4,3-e]pyridine-5-amines, 6 by incorporating pyrazolo-pyridine on isoxazole nucleus with 1,2,3-triazole fragment on pyrazole nitrogen as potential antimicrobial agents. The structures of the newly synthesized compounds have been confirmed by IR, NMR, and mass spectrometry. The compounds 6a-h screened for their in vitro antimicrobial activity show promising activity compared to the standard drugs. Especially, compounds 6g and 6h exhibit high antibacterial and antifungal activity with respect to standard drugs Ciprofloxacin and Fluconazole respectively. Furthermore, molecular docking analysis also supports the data of antimicrobial activity by revealing high binding affinity scores across the entire series.
Synthesis of novel 2(3-methylisoxazol-5-yl)-4,10a-diaryl-2,10a-dihydro-1H-benzo[4,5]oxazolo[3,2-a]pyrazines 5 have been achieved by the reaction of 2,2'-(3-methylisoxaol-5-yl)azanediyl)bis(1-phenylethanones) 3 with o-aminophenol 4 in the presence of CAN catalyst in CH3CN solvent by adopting a new synthetic protocol. The required intermediates 3 are prepared by the interaction of 5-amino-3-methylisoxazole 1 with phenacyl bromides 2 in ethanol in the presence of K2CO3. The structures of newly synthesized compounds 3a-j and 5a-j have been confirmed by IR, 1H and 13C NMR, and EI-MS and from microanalytical data.
