Biological Effects on μ-Receptors Affinity and Selectivity of Arylpropenyl Chain Structural Modification on Diazatricyclodecane Derivatives

Opioid analgesics are clinically used to relieve severe pain in acute postoperative and cancer pain, and also in the long term in chronic pain. The analgesic action is mediated by μ-, δ-, and κ-receptors, but currently, with few exceptions for k-agonists, μ-agonists are the only ones used in therapy. Previously synthesized compounds with diazotricyclodecane cores (DTDs) have shown their effectiveness in binding opioid receptors. Fourteen novel diazatricyclodecanes belonging to the 9-propionyl-10-substituted-9,10-diazatricyclo[4.2.1.1^2,5]decane (compounds 20–23, 53, 57 and 59) and 2-propionyl-7-substituted-2,7-diazatricyclo[4.4.0.0^3,8]decane (compounds 24–27, 54, 58 and 60) series, respectively, have been synthesized and their ability to bind to the opioid μ-, δ- and κ-receptors was evaluated. Five of these derivatives, compounds 20, 21, 24, 26 and 53, showed μ-affinity in the nanomolar range with a negligible affinity towards δ- and κ-receptors and high μ-receptor selectivity. The synthesized compounds showed μ-receptor selectivity higher than those of previously reported methylarylcinnamyl analogs.     

Design,Microwave-Assisted Synthesis and In Silico Prediction Study of Novel Isoxazole Linked Pyranopyrimidinone Conjugates as New Targets for Searching Potential Anti-SARS-CoV-2 Agents

A series of novel naphthopyrano[2,3-d]pyrimidin-11(12H)-one containing isoxazole nucleus 4 was synthesized under microwave irradiation and classical conditions in moderate to excellent yields upon 1,3-dipolar cycloaddition reaction using various arylnitrile oxides under copper(I) catalyst. A one-pot, three-component reaction, N-propargylation and Dimroth rearrangement were used as the key steps for the preparation of the dipolarophiles3. The structures of the synthesized compounds were established by ¹H NMR, ¹³C NMR and HRMS-ES means. The present study aims to also predict the theoretical assembly of the COVID-19 protease (SARS-CoV-2 M^pro) and to discover in advance whether this protein can be targeted by the compounds 4a–1 and thus be synthesized. The docking scores of these compounds were compared to those of the co-crystallized native ligand inhibitor (N3) which was used as a reference standard. The results showed that all the synthesized compounds (4a–l) gave interesting binding scores compared to those of N3 inhibitor. It was found that compounds 4a, 4e and 4i achieved greatly similar binding scores and modes of interaction than N3, indicating promising affinity towards SARS-CoV-2 M^pro. On the other hand, the derivatives 4k, 4h and 4j showed binding energy scores (−8.9, −8.5 and −8.4 kcal/mol, respectively) higher than the M^pro N3 inhibitor (−7.0 kcal/mol), revealing, in their turn, a strong interaction with the target protease, although their interactions were not entirely comparable to that of the reference N3.     

An Insight into All Tested Small Molecules against Fusarium oxysporum f. sp. Albedinis: A Comparative Review

Bayoud disease affects date palms in North Africa and the Middle East, and many researchers have used various methods to fight it. One of those methods is the chemical use of synthetic compounds, which raises questions centred around the compounds and common features used to prepare targeted molecules. In this review, 100 compounds of tested small molecules, collected from 2002 to 2022 in Web of Sciences, were divided into ten different classes against the main cause of Bayoud disease pathogen Fusarium oxysporum f. sp. albedinis (F.o.a.) with structure–activity relationship (SAR) interpretations for pharmacophore site predictions as (δ⁻···δ⁻), where 12 compounds are the most efficient (one compound from each group). The compounds, i.e., (Z)-1-(1.5-Dimethyl-1H-pyrazole-3-yl)-3-hydroxy but-2-en-1-one 7, (Z)-3-(phenyl)-1-(1,5-dimethyl-1H-pyrazole-3-yl)-3-hydroxyprop-2-en-1-one 23, (Z)-1-(1,5-Dimethyl-1H-pyrazole-3-yl)-3-hydroxy-3-(pyridine-2-yl)prop-2-en-1-one 29, and 2,3-bis-[(2-hydroxy-2-phenyl)ethenyl]-6-nitro-quinoxaline 61, have antifungal pharmacophore sites (δ⁻···δ⁻) in common in N1---O4, whereas other compounds have only one δ⁻ pharmacophore site pushed by the donor effect of the substituents on the phenyl rings. This specificity interferes in the biological activity against F.o.a. Further understanding of mechanistic drug–target interactions on this subject is currently underway.     

Chemosensing Properties of Coumarin Derivatives: Promising Agents with Diverse Pharmacological Properties,Docking and DFT Investigation

In this work, a three-component reaction of 3-acetyl-4-hydroxycoumarine, malononitrile, or cyanoacetate in the presence of ammonium acetate was used to form coumarin derivatives. The chemical structures of new compounds were identified by ¹H, ¹³C NMR and an elemental analysis. These compounds were examined in vitro for their antimicrobial activity against a panel of bacterial strains. In addition, these compounds were investigated for antioxidant activities by superoxideradical, DPPH (2,2-Diphenyl-1-picrylhydrazyl), and hydroxyl radical scavenging assays, in which most of them displayed significant antioxidant activities. Furthermore, these compounds were evaluated for anti-inflammatory activity by indirect hemolytic and lipoxygenase inhibition assays and revealed good activity. In addition, screening of the selected compounds 2–4 against colon carcinoma cell lines (HCT-116) and hepatocellular carcinoma cell lines (HepG-2) showed that that 2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4 exhibited good cytotoxic activity against standard Vinblastine, while the other compounds exhibited moderate cytotoxic activity. Docking simulation showed that2-amino-4-hydroxy-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile 4 is an effective inhibitor of the tumor protein HCT-116. A large fluorescence enhancement in a highly acidic medium was observed, and large fluorescence quenching by the addition of traces of Cu²⁺ and Ni²⁺ was also remarked.     

Researches on 1, 2, 4-triazoles

Determination of the acidity constants of 1-aryltetrazolinethiones-5, 4-aryl-1, 2, 4-triazolinethiones-3, 1-aryltetrazolinones-5, 4-aryl-1, 2, 4-triazolinones-3 shows that carbonyl compounds are 10^–1–10^–2 times less acid than compounds with a thione group. Acidities are found to increase considerably, 10³–10⁴ times, on passing from triazole compounds to tetrazole ones. 4-Aryl-1, 2, 4-triazolinones-3 and 1-aryl-tetrazolinones-5 are aminomethylated and cyanoethylated and the reactions found to take place at the amide nitrogen atom.For Part VI see [1].     

Differential pulse polarographic determination of some organotin(IV) compounds in dimethyl sulfoxide

The differential pulse polarographic behavior of two series of organotin(IV) compounds having the general formula R_xSnCl_{4 − x} (R = Me, Ph; x = 1, 2, 3, 4) has been investigated in DMSO. The peaks obtained are recommended for the trace determination of these compounds. Linear calibration curves are obtained over the concentration range 10⁻⁴ –10⁻⁶ M.     

Theoretical calculations of95Mo-NMR chemical shifts for compounds [MoO4−n S n ]2−

Summary Theoretical calculation of⁹⁵Mo-NMR chemical shifts for [MoO_4–n S _n ]^2– (n=0–4) compounds is reported here for the first time on the basis of Fenske-Hall method and Sum-Over-State (SOS) perturbation theory. A systematic decrease in shielding of⁹⁵Mo nuclei with increase of number of sulfur in [MoO_4–n S _n ]^2–, which is observed experimentally, can be reasonably explained by our calculation. A good linear relationship between chemical shifts of calculation and experiment is obtained. The electronic structure and bonding in these compounds are also discussed.Supported by Nature Science Foundation of China     

The Antiproliferative and Apoptotic Effects of a Novel Quinazoline Carrying Substituted-Sulfonamides: In Vitro and Molecular Docking Study

In order to investigate for a new effective and safe anticancer drug, we synthesized a novel series of quinazoline containing biologically active substituted-sulfonamide moiety at 3- position 4a–n. The structure of the newly prepared compounds was proved by microanalysis, IR, ¹H-NMR, ¹³C-NMR and mass spectral data. All the synthesized compounds were evaluated for their in vitro cytotoxic activity in numerous cancer cell lines including A549, HepG-2, LoVo and MCF-7 and normal HUVEC cell line. The two most active compounds 4d and 4f were then tested for their apoptosis induction using DNA content and Annexin V-FITC/PI staining. Moreover, apoptosis initiation was also confirmed using RT-PCR and Western blot. To further understand the binding preferences of quinazoline sulfonamides, docking simulations were used. Among the fourteen new synthesized compounds, we found that compounds 4d and 4f exerted the strongest cytotoxicity against MCF-7 cells with an IC₅₀ value of 2.5 and 5 μM, respectively. Flow cytometry data revealed the ability of compounds 4d and 4f to mediate apoptosis and arrest cell cycle growth at G1 phase. Furthermore, RT-PCR and Western blot results suggested that both 4d and 4f activates apoptotic cell death pathway in MCF-7 cells. Molecular docking assessments indicated that compounds 4d and 4f fit perfectly into Bcl2’s active site. Based on the biological properties, we conclude that both compounds 4d and 4f could be used as a new type of anticancer agent, which provides a scientific basis for further research into the treatment of cancer.     

Design,Synthesis and Molecular Docking Study of Novel 3-Phenyl-β-Alanine-Based Oxadiazole Analogues as Potent Carbonic Anhydrase II Inhibitors

Carbonic anhydrase-II (CA-II) is strongly related with gastric, glaucoma, tumors, malignant brain, renal and pancreatic carcinomas and is mainly involved in the regulation of the bicarbonate concentration in the eyes. With an aim to develop novel heterocyclic hybrids as potent enzyme inhibitors, we synthesized a series of twelve novel 3-phenyl-β-alanine 1,3,4-oxadiazole hybrids (4a–l), characterized by ¹H- and ¹³C-NMR with the support of HRESIMS, and evaluated for their inhibitory activity against CA-II. The CA-II inhibition results clearly indicated that the 3-phenyl-β-alanine 1,3,4-oxadiazole derivatives 4a–l exhibited selective inhibition against CA-II. All the compounds (except 4d) exhibited good to moderate CA-II inhibitory activities with IC₅₀ value in range of 12.1 to 53.6 µM. Among all the compounds, 4a (12.1 ± 0.86 µM), 4c (13.8 ± 0.64 µM), 4b (19.1 ± 0.88 µM) and 4h (20.7 ± 1.13 µM) are the most active hybrids against carbonic CA-II. Moreover, molecular docking was performed to understand the putative binding mode of the active compounds. The docking results indicates that these compounds block the biological activity of CA-II by nicely fitting at the entrance of the active site of CA-II. These compounds specifically mediating hydrogen bonding with Thr199, Thr200, Gln92 of CA-II.     

Photolysis of 2-piperidino- and 2-morpholino-3-methoxy-1,4-naphthoquinones

PMR and¹³C NMR spectroscopy was used to establish the structure of the primary products of the photolysis of 2-piperidino- and 2-morpholino-3-methoxy-l, 4-naph-thoquinones. A scheme for the subsequent dark transformations of these compounds is proposed.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 709–713, March, 1991.     

Separation of pyridine compounds on ion-exchange resins

The reaction of pyridine compounds (pyridine, 4-methylpyridine, 4-hydroxypyridine, 4-carboxypyridine, pyridine-4-aldehyde, and pyridine-4-aldoxime) with KU-2 cation-exchange resins in the H⁺, K⁺, and NH₄ ⁺ forms and with AV-17 anion-exchange resins in the OH^– and Cl^– forms was investigated. A dependence of the maximum partition coefficients of the pyridine compounds on the composition and concentration of the eluent was found. The chromatogram of the separation of a mixture of pyridine compounds on AV-17 (Cl^– form) is presented.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 220–224, February, 1971.     

Ring-Opening Polymerization of ε-Caprolactone and Styrene Oxide–CO2 Coupling Reactions Catalyzed by Chelated Dehydroacetic Acid–Imine Aluminum Complexes

A series of chelated dehydroacetic acid–imine-based ligands L¹H~L⁴H was synthesized by reacting dehydroacetic acid with 2-t-butylaniline, (S)-1-phenyl-ethylamine, 4-methoxylbenzylamine, and 2-(aminoethyl)pyridine, respectively, in moderate yields. Ligands L¹H~L⁴H reacted with AlMe₃ in toluene to afford corresponding compounds AlMe₂L¹ (1), AlMe₂L² (2), AlMe₂L³ (3), and AlMe₂L⁴ (4). All the ligands and aluminum compounds were characterized by IR spectra, ¹H and ¹³C NMR spectroscopy. Additionally, the ligands L¹H~L⁴H and corresponding aluminum derivatives 1, 3, and 4 were characterized by single-crystal X-ray diffractometry. The catalytic activities using these aluminum compounds as catalysts for the ε-caprolactone ring-opening polymerization (ROP) and styrene oxide-CO₂ coupling reactions were studied. The results show that increases in the reaction temperature and selective solvent intensify the conversions of ε-caprolactone to polycaprolactone. Regarding the coupling reactions of styrene oxide and CO₂, the conversion rate is over 90% for a period of 12 h at 90 °C. This strategy dispenses the origination of cyclic styrene carbonates, which is an appealing concern because of the transformation of CO₂ into an inexpensive, renewable and easy excess carbon feedstock.     

Synthesis and Characterization of New Boron Compounds Using Reaction of Diazonium Tetraphenylborate with Enaminoamides

A family of oxazaborines, diazaborinones, triazaborines, and triazaborinones was prepared by reaction of polarized ethylenes, such as β-enaminoamides, with 4-methylbenzenediazonium tetraphenylborates. The reaction conditions (stirring in CH₂Cl₂ at room temperature (Method A) or stirring with CH₃COONa in CH₂Cl₂ at room temperature (Method B) or refluxing in the CH₂Cl₂/toluene mixture (Method C)) controlled the formation and relative content of these compounds in the reaction mixtures from one to three products. Substituted oxazaborines gradually rearranged into diazaborinones at 250 °C. The prepared compounds were characterized by ¹H NMR, ¹³C NMR, IR, and UV–Vis spectroscopy, HRMS, or microanalysis. The structure of individual compounds was confirmed by ¹¹B NMR, ¹⁵N NMR, 1D NOESY, and X-ray analysis. The mechanism of reaction of enaminoamides with 4-methylbenzenediazonium tetraphenylborate was proposed.     

A New Page in the Chemistry of Copper: Compounds Containing [CuCl6]4– and [CuBr6]4– Anions

A review of the methods used to synthesize compounds containing isolated [CuCl₆]^4– and [CuBr₆]^4– anions is given. The results of studies of new compounds using X-ray diffraction analysis, steady-state magnetic susceptibility, EPR, IR, and electronic spectroscopy are discussed.     

Boron(iii) β-diketonate-based small molecules for functional non-fullerene polymer solar cells and organic resistive memory devices

A class of acceptor–donor–acceptor chromophoric small-molecule non-fullerene acceptors, 1–4, with difluoroboron(iii) β-diketonate (BF₂bdk) as the electron-accepting moiety has been developed. Through the variation of the central donor unit and the modification on the peripheral substituents of the terminal BF₂bdk acceptor unit, their photophysical and electrochemical properties have been systematically studied. Taking advantage of their low-lying lowest unoccupied molecular orbital energy levels (from −3.65 to −3.72 eV) and relatively high electron mobility (7.49 × 10⁻⁴ cm² V⁻¹ s⁻¹), these BF₂bdk-based compounds have been employed as non-fullerene acceptors in organic solar cells with maximum power conversion efficiencies of up to 4.31%. Moreover, bistable resistive memory characteristics with charge-trapping mechanisms have been demonstrated in these BF₂bdk-based compounds. This work not only demonstrates for the first time the use of a boron(iii) β-diketonate unit in constructing non-fullerene acceptors, but also provides more insights into designing organic materials with multi-functional properties.

Boron(iii) β-diketonates have been demonstrated to serve as multi-functional materials in NFA-based OPVs and organic resistive memories.     

Synthesis,Antibacterial, and Antioxidant Evaluation of Novel Series of Condensed Thiazoloquinazoline with Pyrido,Pyrano, and Benzol Moieties as Five- and Six-Membered Heterocycle Derivatives

A novel synthesis of thiazolo[2,3-b]quinazolines 4(a–e), pyrido[2′,3′:4,5]thiazolo[2,3-b]quinazolines {5(a–e), 6(a–e), and 7(a–e)}, pyrano[2′,3′:4,5]thiazolo[2,3-b]quinazolines 8(a–e), and benzo[4,5]thiazolo[2,3-b]quinazoloine9(a–e) derivatives starting from 2-(Bis-methylsulfanyl-methylene)-5,5-dimethyl-cyclohexane-1,3-dione 2 as efficient α,α dioxoketen dithioacetal is reported and the synthetic approaches of these types of compounds will provide an innovative molecular framework to the designing of new active heterocyclic compounds. In our study, we also present optimization of the synthetic method along with a biological evaluation of these newly synthesized compounds as antioxidants and antibacterial agents against the bacterial strains, like S. aureus, E. coli, and P. aeruginosa. Among all the evaluated compounds, it was found that some showed significant antioxidant activity at 10 μg/mL while the others exhibited better antibacterial activity at 100 μg/mL. The results of this study showed that compound 6(c) possessed remarkable antibacterial activity, whereas compound 9(c) exhibited the highest efficacy as an antioxidant. The structures of the new synthetic compounds were elucidated by elemental analysis, IR, ¹H-NMR, and ¹³C-NMR.     

Tetrameric copper(II) halide compounds containing (R,S)- and (S)-1-amino-2-propanolate ions

Summary Compounds with the composition CuXL, in which X=Cl^– or Br^– and L=R,S-1-amino-2-propanol andS-1-amino-2-propanol, both with deprotonated hydroxy groups, are described. Magnetic measurements strongly suggest these compounds to have a tetrameric cubane-type structure with a Cu₄O₄ core. The racemic and optically-active compounds show a different magnetic behaviour, most likely originating from different cluster types for the isomers. The results of the i.r., f.i.r. and e.s.r. spectra are in good agreement with the proposed cluster types.     

Ionic Mobility, Phase Transitions, and Superionic Conduction in Solid Solutions (100 ? x)PbF2-xZrF4 and Crystals K2ZrF6, (NH4)2ZrF6, KSnZrF7, and M(NH4)6Zr4F23 (M = Li, Na)

Methods of (¹⁹F, ¹H) NMR and impedance spectroscopy are used to investigate the internal mobility and ionic conduction in solid solutions arising in the system PbF₂-ZrF₄ and polycrystals KSnZrF₇, Li(Na)(NH₄)₆Zr₄F₂₃, and M₂ZrF₆ (M = K, NH₄). Factors responsible for the form of ionic motions and their energetics at 170–550 K are considered. It is established that the phase transitions in these compounds are connected with the crystal transition to a superionic state and that the high ionic (superionic) conductivity of beta phases is due to the diffusion of fluoride ions, ammonium cations, and possibly alkali metal cations. The obtained data testify to a substantial role of chainlike aggregation of anionic groupings and a variableness of structural mechanisms of formation of such chains in fluorozirconates for the development of translational diffusion in these compounds.__________Translated from Elektrokhimiya, Vol. 41, No. 5, 2005, pp. 573–582.Original Russian Text Copyright © 2005 by Kavun, Uvarov, Slobodyuk, Goncharuk, Kotenkov, Tkachenko, Gerasimenko, Sergienko.     

Synthesis and evaluation of in vitro antibacterial activity of novel 2,5-disubstituted-1,3,4-thiadiazoles from fatty acids

A series of new 1-（alkenoyl/hydroxyalkenoyl）-4-benzoyl-thiosemicarbazides 2a-d and 2-benzamide-5-alkenyl/hydroxyalk- enyl-1,3,4-thiadiazoles 3a-d were synthesized from fatty acid hydrazides. Structure of all these compounds was confirmed by IR, IH NMR, Sac NMR, mass spectra and elemental analysis. The bioassay results indicate that some compounds 2e, 2d, 3e and 3d have good antibacterial activity.     

The preparation and characterization of acetylacetonato-bis(η-methylcyclopentadienyl)titanium(IV) complexes

Summary A series of [L₂TiL]⁺X^–compounds where L is the conjugate base of acetylacetone, L=-MeC₅H₄ and X^–= ClO ₄ ^– , BF ₄ ^– , FeCl ₄ ^– , ZnCl₃(H₂O)^–, SnCl ₃ ^– , CdCl ₄ ^2– , HgCl ₄ ^2– , Br^– or I^–, have been prepared by adding X^– to the aqueous solution of [L₂TiL]⁺Cl^–. Conductivity measurements in nitrobenzene for all compounds indicate that these complexes are electrolytes. The i.r. frequencies for various vibrational modes have been assigned. The ligand L appears to be chelating and the titanium atom is essentially tetracoordinate. The bonding in these complexes is discussed.On study leave from S. D. College, Muzaffar Nagar, U.P., India.