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AbstractNovel 6-bromo-imidazo[4,5-b]pyridine derivatives (2-4, 5a-13a, and 6b, 8b-13b) have been synthesized based on a developed systematic approach involving the condensation of 5-Bromo-2,3-diaminopyridine with a suitable aromatic aldehyde in the presence of molecular iodine in water, followed by alkylation reactions using different alkyl dibromide agents. The synthesized compounds were characterized by the NMR spectroscopy technique. The structures of 8a, 9a, 12a,and 11bwere confirmed using monocrystalline X-ray crystallography. Theoretical calculations have been carried out using DFT and TD-DFT methods at the B3LYP/6-31G++(d,p) level of theory. Intermolecular contacts between units of 8a, 9a, 12a, and 11bwere determined through the Hirshfeld surface analysis. The molecular docking study has been performed to determine the binding affinity of 8a, 9a, 12a,and 11binto the binding site of S. aureustyrosyl-tRNA synthetase as a target enzyme, and the results revealed that 9ais the most potent compound among the selected compounds with a binding affinity of −8.74 Kcal/mol.Communicated by Ramaswamy H. Sarma

AbstractThe current work describes the preparation of three unexpected compounds: a tetrasubstituted phenolic compound, an isocoumarin, and a pyranopyridine, bearing various substituent groups obtained through the condensation of 6-methyl-4-hydroxypyran-2-one 1with 2-aminopyridine 2under mild conditions. Plausible mechanisms explaining the formation of these compounds have been presented. Their structures have been elucidated using spectral data and confirmed by crystallographic studies. Furthermore, optimized geometries of and electronic distribution of FMOs orbitals are investigated in the PCM solvent model at the B3LYP/6-311++G(d,p) level of theory. The compounds were tested for their antioxidant and antidiabetic activities. Moreover, the binding interactions between the compounds and α-glucosidase and α-amylase were determined through their docking into the binding sites of the target enzymes using the Autodock package.Communicated by Ramaswamy H. Sarma

AbstractWe have synthesized benzo[d]oxazole derivatives (1–21) through a multistep reaction. Alteration in the structure of derivatives was brought in the last step viausing various substituted aromatic aldehydes. In search of an anti-Alzheimer agent, all derivatives were evaluated against acetylcholinesterase and butyrylcholinesterase enzyme under positive control of standard drug donepezil (IC50= 0.016 ± 0.12 and 4.5 ± 0.11 µM) respectively. In case of acetylcholinesterase enzyme inhibition, derivatives 8, 9and 18(IC50= 0.50 ± 0.01, 0.90 ± 0.05 and 0.3 ± 0.05 µM) showed very promising inhibitory potentials. While in case of butyrylcholinesterase enzyme inhibition, most of the derivatives like 6, 8, 9, 13, 15, 18and 19(IC50= 2.70 ± 0.10, 2.60 ± 0.10, 2.20 ± 0.10, 4.25 ± 0.10, 3.30 ± 0.10, 0.96 ± 0.05 and 3.20 ± 0.10 µM) displayed better inhibitory potential than donepezil. Moreover, derivative 18is the most potent one among the series in both inhibitions. The binding interaction of derivatives with the active gorge of the enzyme was confirmed viaa docking study. Furthermore, the binding interaction between derivatives and the active site of enzymes was correlated through the SAR study. Structures of all derivatives were confirmed through spectroscopic techniques such as 1H-NMR, 13C-NMR and HREI-MS, respectively.Communicated by Ramaswamy H. Sarma

AbstractInhibition of α-amylase enzyme is of key significance for the therapy of diabetes mellitus (DM). Numerous indole-based compounds have earlier been described for broad range of bioactivities. From our previous study, we knew that indole and thiadiazole are potent inhibitors of diabetics II. We design the hybrid molecules of them and synthesized 18 derivatives of indole-based-thiadiazole (1–18). All synthesized compounds were characterized using different spectroscopic methods and evaluated for their α-amylase inhibitory activities. All synthetic compounds, except 4, 13, 15and 16, were found to be strongly active (IC50values in the range of 0.80 ± 0.05 − 9.30 ± 0.20 µM) than the standard drug, acarbose (IC50= 11.70 ± 0.10 µM). Nevertheless, compound 18was found to be inactive. The modes of binding interactions of five most active compounds 2, 3, 5, 10and 17were also studies through molecular docking study. In brief, current study identifies a novel class of α-amylase inhibitors which can be further studied for the treatment of hyperglycemia and obesity.Communicated by Ramaswamy H. Sarma

Bilirubin (BR) is a yellow-to-orange bile pigment produced by hemoglobin breakdown. It circulates in the blood, is absorbed by the liver, and then conjugated to form bilirubin diglucuronide. Its increased level in serum (Hyperbilirubinemia) may considered as an indication of certain diseases such as neonatal jaundice, hepatitis, and severe liver failure with cirrhosis. Thus, the monitoring of BR in plasma is clinically important. Herein, a novel carbon/chitosan paste electrode modified by L-leucine and Albumin (C/Chi-PL-BSA) is synthesized and tested for electrochemical sensitive determination of BR and Uric Acid. Significate sensitivity and important selectivity in the linear range of 1.00–150.00 μM for BR, and 10.00–600.00 μM for UA were obtained. Moreover, micromolar detection limits of 0.40 μM for BR and 1.00 μM for UA were achieved at pH13. The proposed oxidation mechanisms of BR and UA in alkaline media have been supported by DFT calculations at the B3LYP/ 6–31 G(d) level of theory. The easy preparation and high reproducibility made this electrode very appropriate in pharmaceutical preparations for the electrochemical determination of BR. Furthermore, Analyses using human serum were performed, demonstrating a high percentage of recovery.

AbstractAn efficient process for the preparation of a new ethyl 2-((3-(4-fluorophenyl)-6-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)thio) acetate (5) was described. The prepared derivative was synthesized using the S-arylation method. Several analytical techniques, such as NMR, Raman and infrared spectroscopy, were used to characterize this compound. The compound was screened for cytotoxic activity against three human cancer cell lines: human cervical cancer (HeLa), human lung adenocarcinoma (A549) and triple negative breast cancer (MDA-MB-231) cells using an MTT assay. It exhibited potent cytotoxic activity against the tested cell lines with IC50values in the low micromolar range when compared to a standard drug, docetaxel. It also displayed potent inhibitory activity towards VEGFR-2 and EGFR tyrosine kinases, reflecting its potential to act as an effective anti-cancer agent.Communicated by Ramaswamy H. Sarma

Four novel, potential and water-soluble corrosion inhibitors, namely 1-(4-methyl phenyl)-3-(2-pyridin-2-ylethyl) urea (PTPEU), 1-(2-phenyl ethyl)-3-(2-pyridin-2-ylethyl) urea(PEPEU), 1-(benzyl)-3-(2-pyridin-2-ylethyl) urea(BPEU), and 1-(4-Fluoro phenyl)-3-(2-pyridin-2-ylethyl) urea(FPPEU) were synthesized and characterized for the protection of mild steel in 1 M HCl. The inhibition ability of the inhibitors was evaluated using gravimetric, electrochemical impedance spectroscopy, and potentiodynamic polarization techniques. Overall, all inhibitors provided better protection than the control. PEPEU was the most effective corrosion inhibitor studied. The surface morphology of mild steel specimens inhibited and uninhibited was determined by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX), and atomic force microscopy (AFM). AFM, EDX, and SEM studies confirmed the presence of protective films on mild steel surfaces. The influence of temperature on corrosion rate was also studied. The maximum inhibition efficiency of 98.2% was achieved at 303oK for PEPEU with 100 ppm in the weight loss method. The polarization measurements indicated that all inhibitors displayed mixed inhibitor behavior. The Langmuir adsorption isotherm governed the adsorption process on mild steel surfaces. Additionally, a comprehensive computational study was performed to support the experimental results through Density Functional Theory (DFT) and molecular dynamics simulations (MD). The results suggest that the PEPEU is a promising corrosion inhibitor for mild steel in acidic environments.

A new bipyrazolo [1,5‐a]pyrimidine derivative, 2,2′,5′‐trimethyl‐7‐oxo‐4,7‐dihydro‐[6,7′‐bipyrazolo[1,5‐a]pyrimidine]‐3,3′‐dicarbonitrile dihydrate acetic acid solvate (3) has been synthesized via two different methods and characterized by single‐crystal X‐ray diffraction (XRD) and spectroscopic techniques. A plausible reaction mechanism in the synthesis of 3through the two synthetic routes used has been proposed. The XRD analysis reveals that the two bicyclic moieties in 3are close to perpendicular to one another. Some formal double bonds appear localized while others appear to involve some delocalization. In the crystal structure, a layer structure is formed by OH⋯O, OH⋯N and NH⋯O hydrogen bonds, along with weak CH⋯O and π‐stacking interactions. The energy framework indicates that the packing of 3is mainly determined by dispersion interactions between molecules. The frontier molecular orbital analysis shows that 3may act more as a nucleophile than an electrophile. The analysis of the Hirshfeld surface maps and 2D fingerprint plots of 3reveal that intermolecular hydrogen bonding and H⋯H, N⋯H and O⋯H contacts are the major ones between the units of 3. The antibacterial activity of 3is explored by its molecular docking into the binding site of tyrosyl‐tRNA synthetase, where it formed a stable complex with the amino acids of tyrosyl‐tRNA synthetase mainly through hydrogen bonding. A new 2,2′,5′‐trimethyl‐7‐oxo‐4,7‐dihydro‐[6,7′‐bipyrazolo[1,5‐a]pyrimidine]‐3,3′‐dicarbonitrile dihydrate acetic acid solvate is synthesized and a plausible mechanism of its synthesis is proposed. The energy framework indicates that the dispersion interacts between molecules. The frontier molecular orbital analysis shows that the synthesized compound may act as a nucleophile than an electrophile. Molecular docking showed that the synthesized compound may have a potent antibacterial activity.

AbstractHere we report synthesis of three new compounds namely, 1-acetyl-1H-benzimidazolo-2(3H)-one (I), N-(5-acetyl-6-methyl-2-oxo-2H-pyran-4-yl)-N-(2-acetamidophenyl)acetamide (II) and N-(2-acetamidophenyl)-N-2-oxo-2H-pyran-4-yl)acetamide (III) have been synthesized and characterized by single crystal X-ray diffraction. Compounds Iand IIcrystallize in the monoclinic space groups P21/n, and P21/c, respectively, while IIIcrystallizes in the triclinic space group P-1. The theoretical parameters of I–IIIhave been calculated through density functional theory (DFT) by using the hybrid functional B3LYP and basis set 6-311++G**. These theoretical parameters have been compared with the experimental ones obtained by XRD. The significant intermolecular interactions arising in crystal packing are rationalized by means of the Hirshfeld surface analysis method. The major intermolecular contacts in the Hirshfeld surfaces of I–IIIare from H…H contacts. In addition, binding modes of I–IIIwithin Tyrosine-protein kinase JAK2 were investigated using molecular docking and molecular dynamics simulation studies.Communicated by Ramaswamy H. Sarma

Svalbardines A and B (1and 2) and annularin K (3) were isolated from cultures of Poaceicolasp. E1PB, an endophyte isolated from the petals of Papaver dahlianumfrom Svalbard, Norway. Svalbardine A (1) is a pyrano[3,2-c]chromen-4-one, a new analogue of citromycetin. Svalbardine B (2) displays an unprecedented carbon skeleton based on a 5′-benzyl-spiro[chroman-3,7′-isochromene]-4,8′-dione core. Annularin K (3) is a hydroxylated derivative of annularin D. The structure of these new polyketides, along with those of known compounds 4–6, was established by spectrometric analysis, including extensive ESI-CID-MSnprocessing in the case of svalbardine B (2).

Abstract6-Methyl-7H,8H,9H-[1,2,4]triazolo[4,3-b][1,2,4]triazepin-8-onehas been synthesized, characterized by spectroscopic techniques (FT-IR, 1H and 13C NMR) and finally the structure was confirmed by single crystal X-ray diffraction studies. In the title molecule, C6H7N5O, the 7-membered ring adopts a bowl-like conformation. In the crystal, the molecules form stacks along the c-axis direction through offset π-stacking interactions between the 5-membered rings and C–H···N hydrogen bonds. The stacks are associated viaa combination of N–H···N, C–H···O and C–H···N hydrogen bonds. Further, the Hirshfeld surface analysis reveals the nature of molecular interactions and the fingerprint plot provides information about the percentage contribution from each individual molecular contact to the surface. In addition, due to its biological interest the target molecule adenosine A1 receptor was found based on Structural Activity Relationship (SAR) analysis and, further, subjected into molecular docking and molecular dynamics analysis to understand the binding interaction and stability of the molecule in adenosine A1 receptor system. Furthermore, the Density Functional Theory (DFT) calculations were carried for free compound and the compound in active site (single point DFT), to know the internal stability.Communicated by Ramaswamy H. Sarma

Background: Aripiprazole is a quinolinone derivative. It shows a high affinity for neurotransmitters dopamine and serotonin receptors, which can overcome the blood-brain barrier (BBB) to reach the central nervous system (CNS) to exert therapeutic effects. Its radioiodination may lead to high radiochemical yield and improved its affinity. Aripiprazole radioiodination is an aromatic electrophilic substitution. Objective: Herein, we investigate the favorable atom site of the aromatic electrophilic substitution of aripiprazole by calculating the Fukui indices of heavy atoms and ESP charges of the parent molecule. Methods: The calculations have been carried out at the B3LYP/LanL2DZ level of theory. The iodinated aripiprazole structure is confirmed by comparing the experimental and the predicted 1H NMR chemical shifts of the parent molecule and its iodinated forms. Results: Finally, the electronic properties of aripiprazole and its iodinated form were calculated at the same level of theory. Nucleophilic Fukui indices and ESP charges calculations confirm that C8 is the most favorable site of the electrophilic substitution. The calculated electronic properties (e.g, gap energy, electron affinity, and electronegativity) of aripiprazole and its iodinated form reveal the higher reactivity of iodinated aripiprazole compared with aripiprazole. Conclusion: This may explain the higher affinity of iodinated aripiprazole and the increase of its radiochemical yield.

The structure elucidation of three new alkaloids named isoformosaninol (1), formosaninol (2), and longiflorine (3), isolated from the leaves of Uncaria longifloravar. pteropoda(Miq.) Ridsdale, along with their biosynthetic pathways are discussed. Their absolute structures were determined through a combination of physical data interpretation and quantum chemical calculations using the time-dependent density functional theory (TDDFT) method.

Three different simple and polymeric hydrazide derivatives have been synthesized, evaluated and investigated as corrosion inhibitors for mild steel in 1 M hydrochloric acid medium. The corrosion inhibition performance of these additives was evaluated using electrochemical impedance spectroscopy (EIS) and polarizations measurements. The inhibition efficiency obtained from polarization measurement followed the order of PACAH > ACAH > CAH. The inhibition efficiency of the polyhydrazide derivative (PACAH) at concentration of 50 and 500 ppm was found to be 90.66 and 96.79% respectively, while 500 ppm of cyanoacetohydrazide (CAH) was 39.79% and for the monomer N-acryloyl-N′-cyanoacetohydrazide (ACAH) was 88.66%.

To remedy the problem of microbes, humanity has proposed that the use of antibiotics becomes indispensable. In this work, we present six organic compounds derivatives of 8-hydroxyquinoline newly synthesized and characterized by the usual spectroscopic methods. These compounds have been tested as antibacterial agents against six pathogenic strains, namely: E. cloacae, E. coli, K. pneumoniae, P. aeruginosa, S. aureus and A. baumanii. The minimal inhibitory concentrations were calculated and compared with three standard antibiotics (Penicillin G, Norfloxacin,and Erythromycin) by the disk diffusion technique against all used bacterial strains. The results of bioinformatics POM (Petra/Osiris/Molinspiration) bioinformatic analyses show that all compounds exhibited good bioavailability, and less toxicity profiles when compared with Penicillin G. Furthermore, drug likeness analysis suggests that the synthesized 8-hydroxyquinoline derivatives require serious transformation in order to obtain appropriate oral absorption and brain penetration for potential therapeutic applications.