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An efficient route for the difluorinative-hydroxylation through dearomative difunctionalization of imidazopyridine using Selectfluor as fluorine source has been developed in an aqueous medium. The reaction proceeds through ionic followed by radical pathway. The products are obtained in pure form without column purification. The method was successfully applied for a gram-scale production of 3,3-difluoro-2-(4-fluorophenyl)-2,3-dihydroimidazo[1,2- a ]pyridin-2-ol (3m). The Zolimidine drug successfully underwent difluorinative-hydroxylation in high yield. Interestingly, addition of the tetra- n -butyl ammonium halide or NaI or KSCN or NaNO 2 in the reaction provided oxidative functionalization of imidazopyridine wherein Selectfluor acted as an oxidant. The C-3 substituted (Cl, Br, I, SCN and NO) imidazo[1,2- a ]pyridines were prepared in good yields. These two significant reactions provided wide functional group tolerance, metal/ base-free, and green approach. [Display omitted] An efficient route for the difluorinative-hydroxylation through dearomative difunctionalization of imidazopyridine using Selectfluor as fluorine source has been developed in an aqueous medium. The reaction proceeds through ionic followed by radical pathway. The products are obtained in pure form without column purification. The method was successfully applied for a gram-scale production of 3,3-difluoro-2-(4-fluorophenyl)-2,3-dihydroimidazo[1,2- a ]pyridin-2-ol (3m). The Zolimidine drug successfully underwent difluorinative-hydroxylation in high yield. Interestingly, addition of the tetra- n -butyl ammonium halide or NaI or KSCN or NaNO 2 in the reaction provided oxidative functionalization of imidazopyridine wherein Selectfluor acted as an oxidant. The C-3 substituted (Cl, Br, I, SCN and NO) imidazo[1,2- a ]pyridines were prepared in good yields. These two significant reactions provided wide functional group tolerance, metal/ base-free, and green approach. [ABSTRACT FROM AUTHOR]

• Rapid decrease in bubble count for smaller nozzle due to presence of smaller bubbles. • For x ≥ 0.04 m, U c is governed by entrainment & bubble disintegration effects. • For P R ≥ 2, TKE and Reynolds axial stress were more for larger nozzle diameter. • Beyond a critical P R , flashing instability dominates the external flow dynamics. • Presence of coherent structures indicate that the jet is vorticity driven rather than shear. External characteristics of a flashing water jet released in water were studied using Particle Image Velocimetry and Shadowgraphy techniques for different pressure ratios and nozzle diameters. The flow dynamics of such a jet are dominated by vapor bubble formation due to thermal non-equilibrium and phase change processes. In order to gain insights into the physics of such complex flows, experiments were performed and measurements on velocity distribution and turbulence statistics were obtained. The bubble size distributions were also recorded to characterize the bubble disintegration mechanism. Flashing jet emanating from two different nozzle diameters, D = 5 mm and 2 mm, and at three different pressure ratios, P R = 1.5 bar, 2 bar and 2.5 bar, were studied, at a fluid inlet temperature of T o = 380 K. The results revealed that the maximum value of centerline velocity occurs far downstream, at x ≥ 0.02 m from the nozzle exit, due to the presence of vapor bubble formation that leads to an interaction between the liquid and gaseous phases. This is in contrast to a canonical water jet (i.e., without phase change), where the centerline velocity attains a maximum at the nozzle exit. For D = 5 mm, the turbulent kinetic energy (TKE) was higher and the decay rate was slower as compared to D = 2 mm for P R ≥ 2 bar. From the centerline velocity and TKE measurements, a critical injection pressure ratio, P R > 1.5 bar was documented, beyond which the external flow dynamics of the jet is governed primarily by the flashing mechanism. These observations were verified from the bubble size distribution measurements and can be attributed to thermal non-equilibrium and phase change process. Lastly, the presence of coherent structures in the flow reveals that the entrainment dynamics of a flashing jet is dominated by vorticity. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • IC 50 values of the synthesized benzo[ d ]oxazoles in the range of 0.8–2.8 μM in HepG2 cancer cells. • Cell death of TDNSS-10 treated HepG2 cells by specific sub G1 phase cell cycle arrest. • Significant increase of mitochondrial membrane potential of TDNSS-10 treated HepG2 cells to 71.49%. • Effective inhibition of clonogenic growth of TDNSS-10 treated HepG2 cells at 2.5 µM. Abstract 2-Aryl 5-hydroxy benzo[ d ]oxazoles were designed as potential anticancer agents. A one-pot synthesis of these compounds dispenses the need for ortho -disubstituted precursor, aminophenol and proceeds via C N formation as a key step followed by C O cyclization to form benzo[ d ]oxazoles. The single crystal X-ray diffraction study was used to confirm the molecular structure of a representative compound unambiguously. All of these compounds were evaluated for their anti-proliferative properties in vitro against five cancer cell lines as well as noncancerous cells. Most of these compounds showed selective growth inhibition of cancer cells and few of them were found to be promising with IC 50 values in the range of 0.8–2.8 μM, comparable to the known anticancer drug doxorubicin. [ABSTRACT FROM AUTHOR]

A series of amine (1 – 6) and imine (5′ , 6′) based copper(II) complexes with tridentate (NNO) ligand donors were synthesized and characterized using modern analytical techniques. All the complexes were subjected to 2-aminophenol (OAP) oxidation to form 2-aminophenoxazin-3-one, as a functional analogue of an enzyme, phenoxazinone synthase. In addition, a critical comparison of the reactivity using the amine-based complexes with their respective imine counterparts was achieved in both experimental as well as theoretical studies. For instance, the kinetic measurement revealed that the imine-based copper(II) complexes (k cat , 2.4 × 105–6.2 × 106 h−1) are better than amine-based (k cat , 6.3 × 104–3.9 × 105 h−1) complexes. The complex-substrate adducts [Cu(L3)(OAP)] (7) and [Cu(L3 ′)(OAP)] (7′) were characterized for both systems by mass spectrometry. Further, the DFT study was performed with amine- (3) and imine- (3′) based copper(II) complexes, to compare their efficacy in the oxidation of OAP. The mechanistic investigations reveal that the key elementary step to determine the reactivity of 3 and 3′ is the proton-coupled electron transfer (PCET) step occurring from the intermediates 7 / 7′. Further, the computed HOMO-LUMO energy gap of 7′ was smaller than 7 by 0.8 eV, which indicates the facile PCET compared to that of 7. Moreover, the coupling of the OAP moiety using imine-complexes (ΔG R.E = −5.8 kcal/mol) was found to be thermodynamically more favorable than amine complexes (ΔG R.E = +3.3 kcal/mol). Overall, the theoretical findings are in good agreement with the experimental results. The role of electronic and auxiliary ligands in copper(II) complexes were studied for PHS mimicking activity. [Display omitted] • Synthesis and characterization of amine and imine based Cu(II) complexes. • Effective PHS activity with remarkable rate in the oxidation of o -aminophenol. • Reactivity and mechanism of amine vs imine based Cu(II) complexes was studied. [ABSTRACT FROM AUTHOR]

A series of twenty-five 2-azitidinone ( β -lactam) derivatives were synthesized and evaluated for anti-cancer properties against breast cancer, MCF-7 and MDA-MB-231. These β -lactam derivatives depicted significant cytotoxicity in cancer cell lines but not in normal human mammary epithelial cells, MEpiC. Interestingly, derivatives of 2-bromo ethyl acrylonitrile ( 19w ) exhibited - potent anti-proliferative activity with IC 50 , 5.79 ± 0.01 μM in MCF-7 and 6.86 ± 0.009 μM in MDA-MB-231. In addition, an increased expression of pro-apoptotic genes (p53, Bax, Bid) as well as decreased mRNA expression of cyclins D1, E and Cdk 2, 6 along with cell cycle arrest at G 1 phase was observed. 19w treatment has shown higher percentage of Annexin-positive cells indicating induction of apoptosis. Further, docking studies confirmed an interaction between 19w and ATP-binding catalytic site of AKT1. Mechanistically, 19w depicted dose-dependent decrease in phosphorylation of AKT and GSK-3 β and significant decrease in AKT kinase activity. In conclusion, β -lactam derivative 19w is a potential anti-breast cancer therapeutic candidate targeting cell survival pathway (AKT/GSK3 β ). [ABSTRACT FROM AUTHOR]

A series of novel diaziridinyl quinone isoxazole hybrids ( 9a - 9j ) were synthesized starting from 2, 5-dimethoxy acetophenone 1 via Claisen reaction, cyclisation, alkoxy carbonylation, hydrolysis, oxidation and aziridine insertion. All the compounds were screened for antimicrobial, anti-biofilm and cytotoxic activities. Among the screened compounds, the compound 9h showed good antibacterial and anti-biofilm activities with MIC value of 3.9, 3.9, 3.9 and 7.8 μg/mL, respectively, and IC 50 values of 1.9, 2.5, 2.8 and 5.1 μM, respectively, against Staphylococcus aureus MTCC 96, S. aureus MLS-16 MTCC 2940, Bacillus subtilis MTCC 121 and Klebsiella planticola MTCC 530, and also exhibited potent antifungal activity against Candida albicans MTCC 227, C. albicans MTCC 854 and Candida krusei MTCC 3020 equipotent to standard miconazole (MIC value 7.8 μg/mL). All the synthesized compounds exhibited promising cytotoxicity against A549 and PC3 cell lines (IC 50 values between 1 and 4 μM). Compounds 9b and 9j exhibited IC 50 value of 0.5 μM which was similar to that of Mitomycin C against PC3 cell line. [ABSTRACT FROM AUTHOR]

A series of new edaravone derivatives 3 – 7 have been synthesized, characterised using various spectroscopic techniques and screened for their in vitro anti-cancer, antioxidant activities. Structure of 5d was further substantiated through single crystal X-ray diffraction. Among the tested, 5l exhibited pronounced activity against PC3 cancer cells. Compounds 5i , 5l , 7c showed potent activity against A549 cancer cells. Products 5k , 6 , 7c demonstrated good antioxidant activity with MIC values of 18.60, 16.27, 16.07 μg/mL respectively. Further the reported analogues were also tested on normal HEK293T cells and displayed low to good safer profiles. Derivatives 5l and 7c have come out to be safer potent anticancer, antioxidant agents. Additionally, the target products were subjected to their molecular properties prediction and drug likeness by employing Molinspiration and Osiris property explorer toolkits. None of them violated Lipinski’s boundaries classifying the title compounds as potential anticancer and antioxidant agents. [ABSTRACT FROM AUTHOR]

A series of 2,5-disubstituted-1,3,4-thiadiazole derivatives 5a – 5l , 7a – 7e and 9 have been synthesised and screened for in vitro antimycobacterial activity against Mycobacterium smegmatis MC-155. In addition these compounds have also been screened for cytotoxic activity against cancer cell lines HT-29, MDA-MB-231 by MTT colorimetric assay. The compounds are well characterized by spectral analysis viz. 1 H NMR, 13 C NMR, FT-IR, mass and HRMS. Screening results indicate that compounds 5g , 7a possess good antitubercular activity with MIC value 65.74 and 40.86, respectively, compounds 5g , 7a , 7b , 7d , 7e and 9 displayed promising cytotoxic activity against the cell lines tested. 5g and 7a stand out to be potent antimycobacterial and anticancer agents among the tested series. Further the title compounds were also tested on human normal cells HEK293T and are found to be safer with lesser cytotoxicity. It is interesting to observe that compound 5g has come out to be safer, potent anticancer and antimycobacterial agent. [ABSTRACT FROM AUTHOR]

A convenient approach for the synthesis of novel tetracyclic scaffolds incorporating a flavonoid framework with medium sized heterocyclic rings (eight-, nine-, ten- and eleven-membered rings) containing two oxygen atoms from flavonols through alkylation using different dibromoalkanes was described. The synthesized compounds were established based on the spectral data and X-ray crystal structure for 6c . The synthesized compounds were evaluated for their in vitro antimicrobial activity. Docking studies were carried out for most active two compounds 6f and 6i . [ABSTRACT FROM AUTHOR]

A new series of 1,9-acetals of forskolin were synthesized by treating with aromatic and aliphatic aldehydes using Ceric ammonium nitrate as catalyst and evaluated for anticancer and α-glucosidase inhibition activities. Among the synthesized compounds 2a , 2b and 3a showed potential cytotoxic activity towards human cancer cell lines MCF-7 (Human Breast Adenocarcinoma), MDA-MB (Human Breast Carcinoma), HeLa (Human Cervix Adenocarcinoma), A498 (Human Kidney Carcinoma), K562 (Human Erythromyeloblastoid leukemia), SH-SY5Y (Human Neuroblastoma), Hek293 (Human Embryonic Kidney) and WRL68 (Human Hepatic) with IC 50 values ranging between 0.95 and 47.96 μg/ml. Osmotic fragility test revealed compound 3a as non-toxic to human erythrocytes at the tested concentrations of 50 and 100 μg/ml. Compounds 1g (IC 50 value 0.76 μg/ml) and 1p (IC 50 value 0.74 μg/ml) significantly inhibited α-glucosidase in in vitro system. In silico based docking, ADME and toxicity risk assessment studies also showed discernible α-glucosidase activity for compounds 1g , 1p compared to standard acarbose. [ABSTRACT FROM AUTHOR]

Abstract: An ecofriendly green approach for synthesis of substituted pyrano[2,3-c]pyrazoles has been developed via a multicomponent one pot approach in aqueous ethanol medium under totally non-catalytic conditions. The synthesized compounds were evaluated for their antibacterial, anti-inflammatory and cytotoxic activities. [Copyright &y& Elsevier]

Abstract: Synthesis of a series of [1,2,3] triazolo [5,1-c] [1,4]benzoxazepine derivatives have been accomplished by the intramolecular Cu(I)-catalyzed cycloaddition of azido-alkynes derived from salicylaldehyde. The biological profile of these heterocyclic structural scaffolds toward anti-bacterial as well as anti-fungal activity has also been illustrated. [ABSTRACT FROM AUTHOR]

Mixed metal ruthenium-ferrocene complexes with anti-cancer properties. • Six novel and fully characterised hetero-bimetallic Ru-Fe complexes are reported. • The in vitro anticancer activities against two cancer cell lines, HepG2 and HeLa are reported. • 5c showed enhanced cytotoxicity against HeLa cancer cells (IC 50 = 9.34 compared to 31.32 for cis-pt). • 5d showed enhanced cytotoxicity against HepG2 cancer cells (IC 50 = 15.74 compared to 27.95 for cis-pt). A series of ruthenium(II) complexes (5a - 5f) derived from ferrocenyl salicylaldimine ligands (3a - 3f), coordinated in a chelating mode through the deprotonated phenolic oxygen atom and the imine nitrogen, were synthesized and fully characterised. The molecular structures of selected ligands and complexes were also confirmed by X-ray diffraction analysis. The heterobimetallic Ru-Fe complexes 5a - 5f were evaluated for their in vitro anti-cancer activity against human liver cancer (HepG2) and human cervical cancer (HeLa) cell lines and showed better activities compared to the ferrocenyl salicylaldimine ligands. Among the heterobimetallic complexes, 5c and 5d showed enhanced cytotoxicity against HeLa cancer cells (IC 50 value of 9.34 µM compared to 31.32 µM for cisplatin), and HepG2 cancer cells (IC 50 value of 15.74 µM compared to 27.95 µM for cisplatin), respectively. Mechanistic studies indicated compound 5d induced cell cycle arrest in the S phase. Further, compound 5d treatment resulted in increased ROS generation and loss of mitochondrial membrane potential in HepG2 cells. [ABSTRACT FROM AUTHOR]

Towards a quest for establishing new antitubercular agents, we have designed new quinoline–triazole hybrid analogs in a six-step reaction sequence involving versatile reactions like Vilsmeier–Haack and click reaction protocol. The design is based on the structural modification of bedaquiline moiety and involves molecular hybridization approach. The structure of the synthesized product was elucidated by single crystal X-ray diffraction study. The synthesized target compounds were screened for their antitubercular activity against Mycobacterium bovis. Interestingly, two compounds of the series (8d and 8m) showed significant inhibition with MIC of 31.5 and 34.8 μM. Compounds bearing 3-fluoro phenyl and n -octyl groups on the 1,2,3-triazole ring emerged as the most potent leads among the compounds tested. Further these hit compounds were also screened for their cytotoxic effect on human embryonic kindey 293 (HEK293) cells and other cancer cell lines such as HeLa (Cervical), PC3 (Prostate), Panc-1 (Pancreatic) and SKOV3 (Ovarian) indicating to be safer with the minimal cytotoxicity. [ABSTRACT FROM AUTHOR]