Background: An estimated 1 in 8 men may acquire prostate cancer at some point in their lives, making it one of the most common malignancies to affect men globally. The androgen receptor (AR), linked to controlling genes essential for cell survival and proliferation, is a major therapeutic target in prostate cancer. The 1E3G is vital to the development of the disease

Objective: This study aims to computationally investigate potential 1E3G receptor inhibitors for prostate cancer treatment. Using molecular docking, DFT analysis, and ADMET profiling, compounds such as Cianidanol and Gallocatechin are assessed for their binding characteristics and pharmacological interactions to identify promising therapeutic candidates for further development.

Materials and methods: Using a computational ligand-based method, the molecular chemical characteristics of 1E3G inhibition were determined. Potential inhibitors such as Cianidanol and Gallocatechin were investigated from Camellia sinensis (Theaceae) and Phyllanthus amarus (Euphorbiaceae). In this study, the DFT 6-31g(d,p) basis set, ADMET, and the Gaussian 16 software package were utilized to compute the physical, chemical, spectral, and thermodynamic properties of specific ligands. The interaction between ligands and proteins was examined with PyRx, Chimera 1.15. Molecular orbital studies were used to calculate the softness and binding characteristics whereas network pharmacology studies examined the interaction of protein and ligands. Additionally, pharmacokinetics was assessed using renowned web tools such as admetSAR, and ProTox-3.0 for predicting toxicity. Moreover, 100 nanoseconds molecular dynamics simulation analysis using Desmond to ensure the stability of these two compounds.

Results: Based on computational research, drug binding site evaluation, docking score, optimization, and molecular dynamic simulation results Cianidanol(Binding affinity -8.1) and Gallocatechin (Binding affinity -8.4)are the most selective 1E3G inhibitors.

Conclusion: These compounds are required to be studied further to develop a useful 1E3G inhibitor for the treatment of Prostate Cancer.

The gram-negative bacterium called Escherichia coli is part of the intestinal microbiota of humans and warm-blooded animals; for this reason, the most of its strains are harmless. However, the strain of this pathogen that produces Shiga toxins with serotype O157:H7 can cause serious illnesses such as acute bloody diarrhea, which in turn can lead to life-threatening hemolytic uremic syndrome, especially in young children and older adults with a case fatality rate of 3 to 5%. This strain is contracted due to the consumption of spoiled or contaminated food. According to several world health organizations, this bacterium has an incidence of 2.8 million cases per year. Therefore, the present study examined the inhibitory capacity of the effector protein Nlel of enterohemorrhagic E. coli (PDB ID: 3NAW) against a series of aza-heterocyclic derivatives. A theoretical protocol was applied, based on docking and molecular dynamics techniques. This approach yielded several key properties, including the affinity energy, the stability of the compound with respect to the protein (RMSD), the hydrogen bond interactions presented between each of the compounds and the protein, along with the production stage MD simulations. Subsequently, for those compounds with promising properties, the binding free energies were calculated using the MMGBSA method to obtain the interaction strength between each aza-heterocyclic compound and the protein. The results of this study have enabled the identification of compounds with the potential to inhibit the infectious strain under investigation. This finding contributes to our understanding of the protein in question and its potential defense mechanisms.

Insect chitinases are hydrolytic enzymes which are necessary for normal cuticle processing during insect molting – an essential step of insects’ developments. Surprisingly, some chitinases have hydrophobic amino acids residues close to active sites. Thus, here we report about virtual screening results which has involved 30 PDB chitinase structures and some original hydrophobic fluorescent compounds with 7-nitrobenzoxadiazol (NBD) and dansyl scaffolds, which have been synthesized in our group. Docking calculations in semi-automatic virtual screening mode have been done using AutoDock Vina (5x5x5 nm grid box, centered on the chain A ) and FYTdock helper software. N-hexanoyl ciprofloxacin has been found to bind with chitinases from Ostrinia furnacalis (pdb : 7vrg, 6jaw, 6jay, 6jmn, 5y2b; energy of bindings (Ebind) -10.2…-9.7). A visavi of the structure, N-hexanoyl-N’-NBD-piperazine, NpipHex, bind in silico with the enzyme less effectively (pdb codes: 6jaw, 5y2b, 6jay, 5y2c, 3wkz; Ebind -9.3…-8.9), and an open-ring analogue of NpipHex - N-hexanoyl-N’-NBD-ethylenediamine, has demonstrated similar affinity (pdb: 5gpr, 6jmn, 7vrg, 5gqb, 5y2c; Ebind -9.0…-8.7). In the same conditions N-NBD-oleylamine demonstrated less affine binding affinity (pdb: 6jmnc, 6jm8, 5gqb, 7vrg, 6jmb; Ebind -8.6…-8.0), and its counterpart, N-Dansyl-oleylamine , demonstrates better results (pdb: 5gpr, 6jav, 5jqb, 3wl0, 7wrg; Ebind -8.7…-8.3).

These results provide new insights into insect biochemistry of chitinases showing new molecular scaffolds suitable as prototypes as either pest control compounds or molecular tools for their fluorescence-based screening.

This study was supported by GSPSR (Belarus) № 20210560 and the grant from the Ministry of Education (Belarus) No. 20250893.

Allenes are a class of compounds with two cumulated carbon-carbon double bonds, which are versatile synthetic intermediates in organic synthesis. They have shown an interesting reactivity and selectivity affording complex structures in a limited number of steps using a wide variety of transition metals. On the other hand, sulfonyl derivatives are very important compounds as they can be found in sulfones and sulfonamides, two classes of compounds with prominent biological and pharmacological activities. Our research group has reported a gold(I)-catalyzed cyclization of allenic carbamates to obtain 1,3-oxazinan-2-ones. In this context, we decide to study a copper-catalyzed cascade heterocyclization/sulfonylation for the controlled preparation of sulfonyl oxazinanones. Surprisingly, in this work we have isolated a great variety of vinyl sulfones with high selectivity instead of the desired cyclization . These sulfones are obtained by the reaction between N-Boc-allenes and aromatic sodium sulfinates. The reaction is carried out at 100 ºC in a sealed tube, where copper acetate (II) is employed as the catalyst and silver nitrate as the oxidant. Both electron-donating and electron-withdrawing groups are tolerated on the aromatic rings of the carbamates and sodium sulfinates. We were able to control the reactivity of allenes toward the formation of bis(γ-amino-functionalized vinyl sulfones) in the presence of copper salts under radical conditions.

A mechanism of photoreduction of an aliphatic nitro compound — nitromethane — in the presence of a hydrogen donor, dimethylamine, was proposed. Quantum chemical calculations (using the ωB97X-D3/def2-TZVPP method in ORCA) were performed to determine the thermodynamic parameters of the proposed reaction steps. Changes in enthalpy and Gibbs free energy were computed for 12 possible elementary steps, with three key reactions selected for further analysis. Transition states for these key steps were located and reaction energy profiles constructed. The lowest activation energy (6.5 kcal/mol) was found for the hydrogen atom transfer from the methyl group of dimethylamine, while some other stages proceeded without an activation barrier. It was shown that the OH group does not detach directly from the nitrogen atom but through a cascade of rearrangements, including hydroxyl migration. The reaction occurs only for aliphatic nitro compounds due to the presence of an α-hydrogen, which is absent in aromatic analogs. The final mechanism consists of 5 consecutive steps and supports the hypothesis about the specific role of the triplet state of nitromethane in reductive photochemical processes. The study highlights the significance of intramolecular rearrangements in lowering activation barriers. These findings may serve as a basis for further design of light-induced reduction pathways for nitro-containing compounds.

Alzheimer's disease (AD) is a neurodegenerative disease that accounts for more than 80% of dementia cases worldwide. It is a neurological disorder that encompasses various stages of development (mild, moderate, or severe cognitive impairment), including certain psychological and behavioral syndromes such as depression, psychosis, and aggression.The main drug classes currently used to treat AD are acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors.

Advancements in bioinformatics and chemometrics have positioned the in silico approach as a pivotal tool in identifying novel therapeutic compounds. in contemporary pharmaceutical research. Therefore, we conducted a study to evaluate the effects of various newly developed N-substituted 5-chloro-2(3H)-benzoxazolone derivatives on AchE.

The aim of this research paper is to utilize in-silico ADMET profiling to investigate the potential of natural analogues as inhibitors of the the AChE . using the computational techniques such as swissadme. Analysis of selected ligands with the highest affinity for the target was performed to evaluate ADME properties

the calculation of ADME properties proved that these ligands follow the rules: Lipinski, Veber and Egan and confirmed the docking results, this allowed us to select them as being probably the best inhibitors

Furthermore, they may be utilized to create novel pharmaceutical medicines to treat individuals with AD.

Spironaphthoxazines belong to one of the most promising classes of organic photochromes. Their main applications include: optical data recording and storage and switches, smart materials, sensors, photocontrolled drug delivery, biosensors for diagnostics etc. Particularly in medical and related fields, stem from their high photostability, fast switching, and structural versatility. Spironaphthoxazines exist in two primary forms: Closed Spiro (SP) form: colorless and Open Photomerocyanine (MC) form: colored. Upon UV irradiation, temperature, solvent or other stimuli exposure, the spironapthoxazines convert from SP to MC through the cleavage of spiro C-O bond. This transformation changes their molecular properties, enabling specific interactions with other molecules. A series of new spironaphthoxazines have been synthesized and the present work propose the investigation of ten of the new structures. In this work, Density Functional Theory (DFT) calculations was used and the molecules was described in PW91 and 6-311G(d,p) basis sets, [3]. The optimized molecular structure and the energy of individual molecular orbitals were predicted for ten spironaphthoxazine derivatives. HOMO-LUMO analysis with corresponding quantum global chemical reactivity descriptors of the studied molecules was obtained to predict molecular stability and reactivity of the molecules. Also, by DFT the vibrational frequencies, thermodynamic properties, NMR Chemical Shifts of molecules were predicted and the minimum energy pathway between the two geometries of the SP and MC forms with identification of the geometry of the transition state form was calculated. The results obtained based on computations were compared and discussed in order to establish the beneficial traits of possible future applications.

The use of Eaton´s reagent for the selective synthesis of 4-methyl-2-quinolone, avoiding the use of mineral acids or expensive metal catalysts as shown in the literature, was previously reported by our research group [1]. This reagent, which consists in 7.7 % phosphorus pentoxide dissolved in methanesulfonic acid, is easily available and has advantages such as controlled reaction conditions and low environmental impact [2]. In this work, we describe the Gould-Jacobs reaction [3] for the synthesis of 6-substituted ethyl 4-oxo-1,4-dihydroquinoline-3-carboxylate. Thus, the condensation of 4-subtituted anilines and diethyl ethoxymethylenemalonate (EMME) to give the corresponding diethyl anilinomethylene malonate was carried out via neat microwave irradiation (MW) and also under refluxing ethanol, in order to compare the performance of both methods. These intermediates underwent the Eaton's reagent catalyzed cyclisation in good to excellent yields, after 2 hours reaction at 100 °C. For the first step, the MW reaction took only 7 minutes compared to the two hours required for the conventional heating, yet the yields were comparable in almost all cases. The subsequent cyclization reaction using Eaton's reagent has only been reported once to prepare the diethyl 2-((phenylamino)methylene)malonate [4]. Meanwhile, the cyclization of 4-substituted anilinomethylene malonates requires high-boiling solvents such as diphenyl ether or Dowtherm, polyphosphoric acid (PPA) catalysis or even flash vacuum pyrolysis (FVP) [5]. In conclusion, a series of ten 4-quinolone derivatives was obtained in good yields under mild conditions and short reaction times. Many of them possess a pharmacophoric 6-substituent group such as sulfonamide, thiazole and sulfamethoxazole derivatives.

A thiazole–thiophene derivative, (E)-4-(2-(2-(1-(5-chlorothiophen-2-yl)ethylidene)hydrazinyl)thiazol-4-yl)benzonitrile (CTHTBN), was synthesized via a one-pot multicomponent reaction involving 5-chloro-2-acetylthiophene, thiosemicarbazide, and 4-(2-bromoacetyl)benzonitrile. The synthesized compound was characterized by FT-IR, ¹H NMR, and ¹³C NMR spectroscopy, confirming the formation of the target molecule. Density Functional Theory (DFT) calculations at the B3LYP/6-311G(d,p) level were performed to explore the electronic structure and reactivity of CTHTBN. The HOMO and LUMO energies were found to be –5.75 eV and –2.03 eV, respectively, with an energy gap (E_g) of 3.72 eV, suggesting a balanced chemical stability and reactivity. The dipole moment of 7.9381 Debye indicated substantial polarity, favourable for biological interactions. Global reactivity descriptors, including chemical hardness (η = 1.86 eV), chemical softness (σ = 0.5376 eV⁻¹), electronegativity (χ = 3.89 eV), electrophilicity index (ω = 4.07 eV), and maximum charge transfer capacity (ΔN_max = 2.09), further supported the molecule’s electronic competence. Molecular docking studies against Mycobacterium tuberculosis Cytochrome P450 14α-sterol demethylase (CYP51) demonstrated a strong binding affinity with a docking score of –8.7 kcal/mol. The binding interactions involved conventional hydrogen bonds, π–π stacking, π–σ, π–sulfur, alkyl, and π–alkyl interactions, stabilizing the compound within the enzyme’s active site. These findings suggest that CTHTBN holds promising potential as an antimycobacterial agent targeting CYP51 and warrants further biological evaluation.

3-Acetylamino-6-aryl-5,6-dihydrouracils were found to exist in DMSO-d₆ solution as mixtures of four rotamers with an overwhelming predominance of two of them (96 mol%), caused by hindered rotation around the N-N bond (two major rotamers) and around the adjacent amide C-N bond (two minor rotamers). To explain these NMR spectroscopic data, thermodynamic and kinetic parameters for interconversion of all the rotamers of 3-acetylamino-5,6-dihydrouracil as a model compound were determined using the DFT B3LYP/6-311++G(d,p) method in the gas phase and DMSO solution. The calculations showed that the s-cis isomers relative to the amide C-N bond are significantly more stable than the corresponding s-trans isomers. Rotations around N-N bond in both the s-cis and s-trans isomers give two atropisomers in which the acetylamino group and the C(2)-N(3)-C(4) fragment are practically orthogonal. The interconversion between these isomers are characterized by fairly high energy barriers. The rather similar results were obtained from the DFT calculations performed for 3-acetylamino-6-(4-methylphenyl)-5,6-dihydrouracil in DMSO solution. Thus, the rotation around the N-N bond of the s-cis conformers of this compound gives two energetic minima [(6R*,S_a*)- and (6R*,R_a*)-diastereomers] and two transition states. The energy barriers between these diastereomers are in the range of ΔG = 17.65–19.17 kcal/mol (298 K, 1 atm) which are in good agreement with the value (ΔG^≠ = 19.6 kcal/mol) of hindered rotation around the N-N bond for the two major rotamers determined using ¹H NMR spectroscopic data at different temperatures.