New enantioenriched ß-indolyl ketones as aromatase inhibitors: Unraveling heme-ligand interactions by MD simulation and MMPBSA analysis.

A series of enantioenriched ß-indolyl ketones as aromatase inhibitors (AI) is synthesized through the Michael-type Friedel-Crafts alkylation of indole. A highly efficient bifunctionalized amino catalyst is developed to access structurally diverse ß-indolyl ketones in high yields (up to 91%) and excellent enantioselectivity (enantiomeric ratio up to 98:2). All the synthesized compounds demonstrated promising aromatase inhibitory potential, where ortho-substituted analogs (3c and 3e) were found most active with IC50 values of 0.68 and 0.90 µM, respectively. Both of these compounds exhibited significant cytotoxicity (IC50 = 0.34 and 0.37 µM) against the MCF-7 breast cancer cell line in the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. Molecular docking studies of the synthesized compounds demonstrate favorable binding interactions with the estrogens controlling CYP19A1 (3EQM) and metabolizing CYP3A4 (5VCC) enzymes. Molecular dynamic (MD) simulation analysis revealed the essentiality of heme-ligand interactions to build a stable protein-ligand complex. An average root mean square deviation of 0.35 nm observed during a 100-ns MD simulation and binding free energy in the range of -190 to -227 kJ/mol calculated by g_mmpbsa analysis authenticated the stability of the 3c-3EQM complex. ADMET and drug-likeness parameters supported the suitability of these indole derivatives as the drug lead to develop potent inhibitors for estrogen-dependent breast cancer.

Benzimidazolium quaternary ammonium salts: synthesis, single crystal and Hirshfeld surface exploration supported by theoretical analysis.

Owing to the broad applications of quaternary ammonium salts (QAS), we present the synthesis of benzimidazolium-based analogues with variation in the alkyl and alkoxy group at N-1 and N-3 positions. All the compounds were characterized by spectroscopic techniques and found stable to air and moisture both in the solid and solution state. Moreover, molecular structures were established through single-crystal X-ray diffraction studies. The crystal packing of the compounds was stabilized by numerous intermolecular interactions explored by Hirshfeld surface analysis. The enrichment ratio was calculated for the pairs of chemical species to acquire the highest propensity to form contacts. Void analysis was carried out to check the mechanical response of the compounds. Furthermore, theoretical investigations were also performed to explore the optoelectronic properties of compounds. Natural population analysis (NPA) has been conducted to evaluate the distribution of charges on the synthesized compounds, whereas high band gaps of the synthesized compounds by frontier molecular orbital (FMO) analysis indicated their stability. Nonlinear optical (NLO) analysis revealed that the synthesized QAS demonstrates significantly improved NLO behaviour than the standard urea.

Biosorption Potential of Arachis hypogaea-Derived Biochar for Cd and Ni, as Evidenced through Kinetic, Isothermal, and Thermodynamics Modeling.

Biochar derived from plant biomass has great potential for the decontamination of aqueous media. It is the need of the hour to test biochar derived from economical, easily available, and novel materials. In this regard, the present study provides insight into the sorption of two heavy metals, i.e., cadmium (Cd) and nickel (Ni), using native Arachis hypogaea and its biochar prepared through pyrolysis. The effect of different factors, including interaction time, initial concentration of adsorbate, and temperature, as well as sorbent dosage, was studied on the sorption of Cd and Ni through a batch experiment. Characterization of the native biowaste and prepared biochar for its surface morphology and functional group identification was executed using Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). Results revealed the presence of different functional groups such as -OH on the surface of the adsorbent, which plays an important role in metal attachment. SEM reveals the irregular surface morphology of the adsorbent, which makes it easy for metal attachment. Thermogravimetric analysis shows the stability of A. hypogaea biochar up to 380 °C as compared with native adsorbent. The adsorption efficacy of A. hypogaea was found to be higher than that of native A. hypogaea for both metals. The best adsorption of Cd (94.5%) on biochar was observed at a concentration of 40 ppm, an adsorbent dosage of 2 g, a contact time of 100 min, and a temperature of 50 °C. While the optimum conditions for adsorption of Ni on biochar (97.2% adsorption) were reported at a contact time of 100 min, adsorbent dosage of 2.5 g, initial concentration of 60 ppm, and temperature of 50 °C. Results revealed that biochar offers better adsorption of metal ions as compared with raw samples at low concentrations. Isothermal studies show the adsorption mechanism as physical adsorption, and the negative value of Gibb's free energy confirms the spontaneous nature of the adsorption reaction. An increase in entropy value favors the adsorption process. Results revealed that the sorbent was a decent alternative to eliminate metal ions from the solution instead of costly adsorbents.

New azole-derived hemiaminal ethers as promising acetylcholinesterase inhibitors: synthesis, X-ray structures, in vitro and in silico studies.

A new class of azole-derived hemiaminal ethers is designed as acetylcholinesterase (AChE) inhibitors. The synthesized compounds exhibited remarkable inhibitory activity against acetylcholine. Chiral hemiaminals (3d and 3i) based on (R)-menthoxymethyl group exhibit excellent inhibition with IC50 values of 0.983 ± 1.41 and 1.154 ± 0.89 µM. Similarly, butoxymethyl derivatives 3a, 3f and 3h, also showed promising inhibition comparable to the standard drug, Donepezil. In silico studies were performed to understand the mode of interactions with the target proteins, where menthoxymethyl azoles 3d and 3i demonstrated the highest docking scores. Molecular dynamics simulations displayed the stable ligand-protein complex of 3i with effective binding interactions. The bioavailability and pharmacokinetic parameterssupported the suitability of these small molecule inhibitors to develop cost-effective drug leads for Alzheimer's disease (AD). MTT assay substantiated the non-cytotoxic nature of the compounds. The synthesized compounds are extensively characterized by 1H NMR, 13C NMR and mass spectral data and SC-XRD.Communicated by Ramaswamy H. Sarma.

Green Synthesis: The Antibacterial and Photocatalytic Potential of Silver Nanoparticles Using Extract of Teucrium stocksianum.

Green synthesis is one of the promising pathways for biologically active nanoscale materials. Herein, an eco-friendly synthesis of silver nanoparticles (SNPs) was carried out using an extract of Teucrium stocksianum. The biological reduction and size of NPS were optimized by controlling the physicochemical parameters such as concentration, temperature, and pH. A comparison of fresh and air-dried plant extracts was also undertaken to establish a reproducible methodology. The biosynthesized SNPs were characterized by UV-Vis spectroscopy, FT-IR, SEM, DLS, and XRD analyses. The prepared SNPs exhibited significant biological potential against multi-drug-resistant pathogenic strains. The results revealed that the biosynthesized SNPs exhibit high antimicrobial activity at low concentrations compared to the parent plant extract. Minimum inhibition concentration (MIC) values were found between 5.3 µg/mL to 9.7 µg/mL for the biosynthesized SNPs, whereas the aqueous extract of the plant showed many high values of MIC, i.e., between 69 and 98 µg/ML. Furthermore, the synthesized SNPs were found efficient in the photolytic degradation of methylene blue under sunlight.

Formulation, Statistical Optimization, and In Vivo Pharmacodynamics of Cydonia oblonga Mucilage/Alginate Mucoadhesive Microspheres for the Delivery of Metformin HCl.

In recent years, attention has shifted toward the utilization of natural polymers for encapsulation and sustained release of health-hazardous drugs. The purpose of this work is to define and assess the sustained delivery potential and mucoadhesive potential of a Cydonia oblonga mucilage (COM) and sodium alginate (Na-Alg)-constituting polymeric delivery carrier of antidiabetic drugs with a specific end goal to retain metformin HCl in the stomach while expanding the drug's bioavailability. Metformin HCl was encapsulated in mucoadhesive microspheres by an ionic gelation method. Polymers with different combinations were tried, and the resulting mucoadhesive COM/Na-Alg microspheres were assessed for particle size (mm) PS/Y1, drug encapsulation efficiency DEE (%)/Y2, and in vitro percentage cumulative drug release R12h/Y3 using Drug Design Expert software version 10. The response surface methodology by a 32-central composite design predicted optimal synthesis parameters for the microspheres to be 295 mg for COM and 219 mg for Na-Alg. An optimized formulation was prepared under these conditions and used to evaluate the micrometric properties, morphology and structural characteristics, swelling behavior, in vitro drug release, and kinetics. Acute toxicity studies were carried out on blank COM/Na-Alg microspheres to deem them safe for in vivo studies. The DEE (%) was calculated to be 85.8 ± 1.67, whereas scanning electron microscopy (SEM) showed a coarse surface with characteristic wrinkles and cracks with an optical microscopic particle size of 0.96 ± 2.45. The ex vivo tests showed great mucoadhesive properties and good swelling behavior with pH-responsive drug release and a significant reduction in in vivo blood glucose levels. The results advocated the use of optimized microspheres to enhance the bioactivity with a possible dose reduction, making it less symptomatic, reducing the expense of the treatment, and subsequently facilitating better patient compliance.

Synthesis, characterization, and in vitro anti-cholinesterase screening of novel indole amines.

The present study involved the targeted synthesis and characterization of novel indole amines with anti-acetylcholinesterase profiling. A series of proposed indole amines was virtually screened against human acetylcholinesterase. A few indole amines (23, 24, and 25) showing strong enzyme binding in the in silico studies were synthesized in the laboratory and characterized using spectroscopic (IR, UV, NMR, single crystal XRD) and spectrometric (EIMS, HR-EIMS) methods. The indole amine 23 was crystallized from EtOH and analyzed with single crystal XRD. These ligands interacted with the PAS site in the enzyme, and their binding may disrupt the activity. The in vitro acetylcholinesterase inhibition studies revealed that the IC50 values for indole amines 25 and 24 (4.28 and 4.66 µM, respectively) were comparable to that of galantamine (4.15 µM) and may be studied further as cost-effective acetylcholinesterase inhibitors.

A facile microwave assisted synthesis and structure elucidation of (3R)-3-alkyl-4,1-benzoxazepine-2,5-diones by crystallographic, spectroscopic and DFT studies.

The use of microwave (MW) irradiation in organic synthesis has become increasingly popular within the pharmaceutical and academic arenas because it is a new enabling technology for drug discovery and development. It is a rapid way of synthesis, which involves faster reaction rates and high selectivity to conventional heating method of syntheses. The MW-assisted 7-exo-tet cyclization of N-acylanthranilic acids afforded (3R)-3-alkyl-4,1-benzoxazepines-2,5-diones in very short duration (20 min) with extraordinary high yields in comparison to conventional heating mode of synthesis. The method development, comparative yields of MW-assisted and thermal method of syntheses, crystallographic, spectroscopic and density functional theory (DFT) studies are reported herein. Four novel compounds with chemical formulas C10H9BrClNO35m, C19H19NO36e, C13H14ClNO36h and C12H11Br2NO36h were synthesized, validated by 1HNMR, 13CNMR, FT-IR, UVVis, EIMS spectroscopic techniques and confirmed by using single crystal X-ray diffraction (SC-XRD) study. The DFT and TDDFT calculations at B3LYP/6-311 + G(d,p) level of theory were performed for comparative analysis of spectroscopic data, optimized geometries, frontier molecular orbitals (FMOs), natural bond orbital (NBO) analysis and nonlinear optical (NLO) properties of 5m, 6e, 6h and 6o. Overall, experimental findings were supported nicely by corresponding DFT computed results. The NBO analysis confirmed that the presence of non-covalent interactions, hydrogen bonding and hyper- conjugative interactions are pivotal cause for the existence of 5m, 6e, 6h and 6o in the solid-state. NLO analysis showed that 5m, 6e, 6h and 6o have significant NLO properties as compared to prototype standard compound which disclosed their potential for technology related applications.

Nucleophilic phenylation: a remarkable application of alkoxymethyltriphenylphosphonium salts.

A new application of α-alkoxymethylphosphonium salts in the nucleophilic phenylation of carbonyl compounds is demonstrated. Phenylation of aldehydes, ketones and acyl halides were studied by employing α-alkoxymethyltriphenylphosphonium halides in the presence of lithium hydroxide. New application of α-alkoxymethyltriphenylphosphonium salts. Metal-free, mild and selective phenylation. Easy preparation and handling of the reagent.

Supramolecular interaction of non-racemic benzimidazolium based ion pairs with chiral substrates.

A series of novel benzimidazolium-based non-racemic ionic liquids (ILs) was synthesized from low-cost chiral terpenoid alcohols and fully characterized by the use of a wide variety of techniques, such as DSC, ESI-MS, ATR FT-IR, polarimetry as well as 1H and 13C NMR spectroscopy. The ILs were investigated as chiral shift agents for the chiral recognition of racemic mixtures of Mosher's acid potassium salt by 19F NMR spectroscopy, leading to high splitting values of the CF3 signal. Supramolecular interactions between salt and H-C2 of chiral benzimidazolium cation are responsible for the chiral recognition, as was demonstrated by experimental evidences. Indeed, the enantiomeric excess value of enantioenriched substrates depends mainly on the strength of the contact ion pairs.

Facile synthesis of α-alkoxymethyltriphenylphosphonium iodides: new application of PPh3/I2.

An efficient one pot method for the synthesis of α-alkoxymethylphosphonium iodides is developed by using PPh3/I2 combination at room temperature. Reaction conditions are found general to synthesize wide range of structurally variant alkoxymethylphosphonium iodides in high yield (70-91%). These new functionalized phosphonium salts are further used in stereoselective synthesis of vinyl ethers as well as in carbon homologation of aldehydes.

Microbial Transformations of (+)-Isomenthol by Fusarium lini and Rhizopus stolonifer.

Microbial transformation of (+)-isomenthol (1) by various strains of fungi was investigated. Fusarium lini has successfully converted compound 1 into a new metabolite, 5α-hydroxyisomenthol (2), and a known metabolite, 1α-hydroxyisomenthol (3), whereas incubation with Rhizopus stolonifer only yielded metabolite 3. The transformed metabolites were structurally characterized on the basis of their spectral data.

3,6-Dimethyl-o-phenyl-enedimethanol.

The title compound, C(10)H(14)O(2), synthesized by reduction of 4,7-dimethyl-2-benzofuran-1,3-dione, crystallizes with two independant mol-ecules in the asymmetric unit, both showing an intra-molecular O-H⋯O hydrogen bond. The crystal packing is stabilized by O-H⋯O hydrogen bonds.