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The purpose of this study was to report the clinical characteristics and long-term visual outcomes in a cohort of children with idiopathic intracranial hypertension (IIH).Retrospective, observational cohort study.Consecutive children who met the diagnostic criteria for definite IIH at a tertiary care pediatric hospital between 2009 and 2020.The charts of pediatric patients with IIH were reviewed. The main outcome measure was long-term visual impairment, with an analysis of clinical features by age and risk factors for a poor visual outcome.There were 110 children (75 females) with IIH. At presentation, younger children with IIH were less likely to present with headaches (p = 0.01) and more likely to be asymptomatic (p = 0.03). There was a strong association with female sex (p 0.001) and higher body mass index (p 0.001) in adolescents in comparison to younger children. Of the 90 patients with long-term visual outcome data, only 8 (9%) had evidence of mild visual impairment (1 loss of visual acuity, 7 loss of visual field) with no cases of severe visual impairment. On risk factor analysis, the only variable associated with a poor visual outcome was greater severity of papilledema at diagnosis.In this large series of pediatric IIH, the long-term visual outcomes were favourable, with evidence of mild visual impairment in less than 10% of patients.

A Novel class of 1,4-disubstituted 1,2,3-triazoles have been synthesized in good to excellent yields via Cu(I) accelerated azide-alkyne click chemistry reaction strategy. The newly synthesized compounds were assessed for their in vitro antimicrobial activity against five Gram-positive, seven Gram-negative bacteria and three fungi. Most of the synthesized compounds displayed significant activity against the tested Gram-positive and Gram-negative bacteria. Molecular docking study revealed that all docked compounds are bound efficiently with the active site of Topoisomerase IV (4EMV) receptor with the observed the free energy of binding from −7.79 to −9.44 kcal/mol. Interestingly, compound 13a forms four hydrogen bonds and displayed high binding energy (−9.44 kcal/mol) with the Topoisomerase IV (4EMV) receptor which correlated with their in vitro antimicrobial assays.

Rhodium-catalysed decarbonylative annulation of isatoic anhydrides with alkynes through C-H activation for the synthesis of aminoisocoumarins was developed. This enables the gram-scale transformation to iodoisocoumarin which is a vital building block in transition-metal-catalysed cross couplings. These compounds exhibit blue-emitting luminescence properties.

The rapid development in the computer technology and its applications in the production system have become flexible in product variety. The flexible production system may take time in setting up the machine to the change in the arrived job. It is often desirable to change the sequence of jobs to save setup cost and time. Conveyor system is the commonly used advanced material handling system that moves jobs from one station to other stations. The conveyor systems used may be of converging or diverging or combination of converging and diverging depending on the type of applications. Most of the assembly operations require converging and diverging type of conveyors. The performance of the conveyor system depends on the elements of the conveyor system and its operational parameters. The present work addresses the effect of dynamic job sequencing in a converging-diverging conveyor system with the objective to reduce the setup cost and its associated time. Discrete event simulation software has been used to model, simulate and investigate the effect of operational parameters associated with converging-diverging conveyor system. Three different models have been considered for studying the effect of different elements in the converging-diverging conveyor system along with dynamic job sequencing based on sequencing heuristics.

One of the important aims of drug discovery for cancer is to find therapeutic agents from natural products that are effective and safe for cancer treatment. In the current study, an alkaloid, 2-acetyl-benzylamine, isolated from Adhatoda vasica, was screened for potent anticancer properties against leukemia cells. We used seven different types of leukemia cells such as CEM, NB-4, MOLM-14, Jurkat, IM-9, K562 and HL-60 for cytotoxic studies. 2-acetyl-benzylamine showed significant cytotoxic properties against MOLM-14 and NB-4 cells with IC50 values of 0.40 and 0.39mM at 24h when compared to other tested cells, respectively. Apoptosis was confirmed by annexin V-FITC/PI kit using flow cytometry and confocal microscope in MOLM-14 and NB-4 cells. In addition, 2-acetyl-benzylamine induced cell cycle arrest at G2/M phase in MOLM-14 cells and G0/G1 phase in NB-4 cells. Apoptosis mechanism was confirmed by RT-PCR and Western blot analysis. Treatment with 2-acetyl-benzylamine decreased the Bcl-2 activity and increased the Bax expression; cytochrome c was released and caspases-3 was activated in MOLM-14 and NB-4 cells. Besides, 2-acetyl-benzylamine inhibited the expression of JAK2/STAT3 in MOLM-14 and NB-4 cells. In vivo administration of 2-acetyl-benzylamine inhibited the growth of MOLM-14 cells in xenograft mice model. Molecular docking study has been performed to investigate the binding mode and to estimate the binding energy of 2-acetyl-benzylamine with the active site of JAK-2, AKT1, FLT3 and Bcl-2. The above findings proved that 2-acetyl-benzylamine could be developed as a potential therapeutic agent against cancer.

A facile ruthenium(II)-catalyzed regiospecific C–H/O–H oxidative annulation methodology was developed to construct isochromeno[8,1-ab]phenazines. This methodology delivers various advantages, such as scope for diverse substrates, tolerance to a range of functional groups, stability under air, and yields regioselective products. This methodology was successfully applied to synthesize far red (FR) fluorescent probes for live cancer cell imaging. The synthesized compounds displayed notable fluorescence properties in solution and thin-film. Their application in live cancer cell imaging was investigated using various cancer cell lines. The synthesized compound showed prominent FR fluorescence, with high quantum yield, and exhibited better cell-imaging properties, with excellent biocompatibility.

In our earlier studies, we have shown that the introduction of amino moieties at carboxylic acid of 4,5-diarylthiophene-2-carboxylic acid significantly improved the anti-inflammatory activity of the compound against the standard drug diclofenac sodium. In the present study, we have synthesized new derivatives of 4,5-diarylthiophene-2-carboxylic acid by modifying the hydroxyl group of the phenyl ring and carboxylic acid group of the thiophene ring. A series of novel 4,5-diarylthiophene-2-carboxylic acid derivatives containing bis-allyloxy and hydroxypropoxy with methyl or ethyl ester moieties were synthesized, characterized and subsequently evaluated for anti-inflammatory and antioxidant property. Among the novel compounds, the inhibition of bovine serum albumin denaturation assay revealed that the compound 4,5-bis(4-(3-hydroxypropoxy)phenyl)thiophene-2-carboxylic acid (15) and ethyl ester (13) having anti-inflammatory activity better than the standard drug diclofenac sodium. The antioxidant screening showing 4,5-bis(4-(allyloxy)phenyl)thiophene-2-carboxylic acid (10), 4,5-bis(4-(3-hydroxypropoxy)phenyl)thiophene-2-carboxylic acid methyl ester (11) and 4,5-bis(4-(3-hydroxypropoxy)phenyl)thiophene-2-carboxylic acid ethyl ester (13) exhibited a slightly moderate antioxidant activity than standard ascorbic acid. Molecular docking analysis was performed for the synthesized compounds with the cyclooxygenase-2 (COX-2) receptor (PDB 1D: 1PXX). Docking studies revealed that all the synthesised compounds exhibit greater binding affinity than the standard drug. Particularly, the compound ethyl 4,5-bis(4-(allyloxy)phenyl)thiophene-2-carboxylate (8) and allyl 4,5-bis(4-(allyloxy)phenyl)thiophene-2-carboxylate (9) having high free energy binding of −10.40 and −10.48 Kcal/mol, respectively. Synopsis: A new series of bis-allyloxy and hydroxypropoxy substituted 4,5-diarylthiophene-2-carboxylic acid derivatives were synthesized, characterized, evaluated their in vitro anti-inflammatory and anti-oxidant activity, and performed molecular docking study.

Herein, synthesis of new hybrid pharmocophores by merging Baylis–Hillman and click chemistry under ball-milling conditions was accomplished. The substrate scope of the reaction was broadened to include alkyl, benzyl, and aryl groups. Catalytic amount of CuO nanoparticles (CuONPs < 50 nm), which was used to carry out the click reaction, could be easily recovered by simple centrifugation, and CuONPs were found to be catalytically active for almost 6 cycles. The highlights of the proposed protocol are as follows: (i) solvent-free reaction conditions, (ii) short reaction times, (iii) no rigorous solvent extraction, (iv) good to excellent chemical yields, (v) 100% atom economy, (vi) CuONP recyclability, (vii) good enantioselectivity, and (viii) no need for high temperatures. Overall, the developed protocol significantly broadens the scope of mechanochemistry as it involves two dissimilar reactions with equal aplomb in a sustainable fashion. Biological assays and in silico studies of the synthesized compounds were also performed to showcase the efficacy of the synthesized compounds as antimicrobial agents.

New 1,4-disubstituted &beta, pyrrolidino-1,2,3-triazoles were synthesized using a reusable copper-iodide-doped neutral alumina catalyst. Synthesis of diversely substituted triazoles and recyclability of CuI catalyst explains the broad scope of this protocol. The synthesized compounds were screened for their antimicrobial and anticancer properties. Most of the compounds showed significant antimicrobial activities against all the tested microorganisms compared to standard drugs. Furthermore, compounds 5a, 5e, 5g, 5h, 5i, and 5j showed moderate to potent activities against A549 and HepG-2 cells. In addition, compounds 5g and 5h displayed potential cytotoxicity activity against A549 cells with IC50 values of 72 &plusmn, 3.21 and 58 &plusmn, 2.31 &micro, M, respectively. The molecular docking study revealed that some of the synthesized compounds exhibited comparable binding as co-crystalized ligands with the DNA topoisomerase IV and anaplastic lymphoma kinase receptors.

Thinning of the retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GCIPL) occur in the chronic phase after optic neuritis (ON) in children and reflect neuroaxonal injury. The objective of this study was to describe changes in RNFL and GCIPL thickness in the acute phase following pediatric ON.Data were collected prospectively from consecutive children presenting with ON as part of an incident acquired demyelinating event. Children with a final diagnosis of multiple sclerosis (n = 9, 10 ON-affected eyes) or monophasic demyelination (n = 16, 25 ON-affected eyes) who underwent spectral-domain optical coherence tomography (OCT) testing within 30 days of symptom onset were included. Standardized visual assessment was performed at presentation and 6-18 months follow-up. OCT measures were compared to those of healthy controls (n = 25, 50 eyes).Median (interquartile range [IQR]) global RNFL thickness was increased in ON-affected eyes (155 μm [114-199 μm]) compared to control eyes (104 μm [98.5-107.5 μm]; p 0.0001). Compared to controls, fellow eyes demonstrated a reduced temporal quadrant RNFL thickness (59 μm [53-72 μm] versus 71.5 μm [65-81 μm]; p = 0.013) and lower GCIPL thickness (80.5 μm [74-88 μm] versus 87 μm [85-89 μm]; p = 0.003). The ON-affected eyes of children with monophasic demyelination demonstrated a greater global RNFL thickness (183.5 μm [146.5-206 μm]) compared to the ON-affected eyes of children with multiple sclerosis (108.5 μm [95-124 μm]; p = 0.01). OCT measures at presentation did not predict low-contrast visual acuity nor color vision at 6-18 months follow-up.Children with multiple sclerosis show less RNFL swelling in their ON-affected eyes at onset compared to children with monophasic demyelination. Lower GCIPL and temporal RNFL thickness in the clinically unaffected eyes of those children with unilateral ON suggests the presence of pre-existing neuroaxonal injury in children presenting with a first episode of ON. This finding may be driven by the subset of children with multiple sclerosis.

A facile eco-friendly approach for the regio- and stereoselective synthesis of structurally intriguing novel spiropyrrolidinoquinoxaline tethered indole hybrid heterocycle has been accomplished via a cascade reaction sequence involving 1,3-dipolar cycloaddition as the key step. Structural elucidation of the synthesized spiroheterocycle was performed by NMR spectroscopy, mass spectrometric analysis and the stereochemistry of asymmetric carbons have been confirmed by single crystal X-ray diffraction analysis. The mechanistic rationalization for the formation of spiroheterocyclic hybrid was investigated through density functional theory (DFT) calculations. In addition, the synthesized spiroheterocyclic hybrid was tested for its cholinesterase inhibitory activity against ChEs and displayed good activity when compared to the standard drug galantamine.

A series of novel 4,5-diarylthiophene-2-carboxamide containing alkyl, cycloalkyl, aryl, aryl alkyl and heterocyclic alkyl moieties were synthesized, characterized and subsequently evaluated for anti-inflammatory property. Among the novel compounds, the inhibition of bovine serum albumin denaturation assay revealed that the aryl and aryl alkyl derivatives of 4,5-diarylthiophene-2-carboxamide showed anti-inflammatory activity comparable to the standard drug diclofenac sodium whereas alkyl and cycloalkyl amide derivatives showed less activity. Docking studies with these compounds against cyclooxygenase-2 receptor (PDB 1D: 1PXX) indicated that they exhibit specific interactions with key residues located in the site of the COX2 structure, which corroborates the hypothesis that these molecules are potential ligands of COX2. The analysis of the docking results, which takes into account the hydrophilic and hydrophobic interactions between the ligands and the target, identified N-(4-bromophenyl)-4,5-bis(4-hydroxyphenyl)thiophene-2-carboxamide (6k) having high binding free energy of −11.67 kcal /mole (comparable with standard diclofenac sodium) and the best docking score, indicating effective binding of the compound 6k at the active site.

A hybrid pharmacophore approach for the synthesis of isomeric pyranoindolones was achieved by employing gold(III) chloride-catalyzed cycloisomerization of alkyne-tethered indole carboxylic acids in good to excellent yield. All the synthesized compounds were evaluated for their tumor cell growth inhibitory activity against human cervix adenocarcinoma (HeLa) which revealed that three compounds exhibited activity comparable with the standard cis-platin (IC50 = 0.08 μM). Molecular docking of all the compounds in Vaccinia H1-Related (VHR) Phosphatase receptor also supported that compound 7d as the most active with a free energy of binding as −8.27 kcal/mol.

A novel series of Mannich derivatives of 3a–g and 3a′–g′ were designed and synthesized from pseudophenylpropanolamine (Ψ-PPA). The stereo chemical aspects of the synthesized compounds were studied and all compounds were well characterized with respect to spectral techniques. All Mannich derivatives, 3a–g and 3a′–g′ were evaluated for their anti-proliferative activity against A549 and HepG-2 cells. Among the tested compounds, 3a showed significant anti-proliferative activity against HepG-2 cells at 25 μM when compared to other compounds. The treatment of 3a exhibited morphological changes, nuclear condensation, colony formatting ability, apoptosis and cell cycle arrest at G2/M phase in HepG-2 cells. Besides, 3a triggered mitochondrial mediated apoptotic pathway as indicated by down regulation of Bcl-2, up-regulation of Bax, and release of cytochrome c and caspases-3. Furthermore, 3a effectively suppressed the cell proliferation and cell growth via JAK2/STAT3 signaling pathway in a time and dose dependent manner. In vivo administration of 3a inhibited tumor growth without significant change in body weight in HepG-2 xenograft mice model. Molecular docking studies revealed that good binding energies of compound 3a against JAK2 (−6.10 kcal mol−1) and Bcl-2 (−6.04 kcal mol−1) receptors. Taken together, 3a possessed potent antitumor activity; it could be a promising lead candidate for the potential treatment of human hepatocellular carcinoma.

Two novel pyrazole based thiourea palladium(II) complexes, [PdCl(PPh3)(C9H8NO2S-pz)] (1) and [PdCl(PPh3)(C14H10NO2S-pz)] (2) [pz = pyrazole (C3H2N2)] have been obtained unexpectedly from chromone thiosemicarbazones (L1 and L2) and [PdCl2(PPh3)2]. The compounds have been fully characterized by physicochemical studies. The single crystal X-ray diffraction and spectral studies revealed square planar geometry for the complexes. The conversion of chromone thiosemicarbazone into pyrazole based thiourea might have happened through coordination to palladium(II) ion after enolization, Michael addition and ring opening followed by cyclization. To the best of our knowledge, this is the first report for the conversion of chromone thiosemicarbazone into pyrazole based thiourea moiety. Plausible mechanism was proposed based on the spectroscopic studies. Calf thymus (CT) DNA binding of the compounds was explored using various spectroscopic and molecular docking methods. DNA cleavage studies suggested that complexes 1 and 2 had the capacity to cleave the supercoiled DNA (pUC19) to its naked form. In vitro cytotoxic property of the ligands and complexes has been evaluated against three human cancer cells such as A549, HepG-2 and U937. Complex 2 exhibited potent cytotoxic activity against HepG-2 cells with the IC50 value of 10.4 μM. In addition, mechanistic studies showed that complex 2 induced apoptosis through mitochondrial signaling pathway in HepG-2 cells. Beneficially, complex 2 showed less toxicity against human lung (IMR90) normal cells and hence it emerges as a potential candidate for further studies.

The synthesis of substituted isoxazoles and pyrazoles through a general cycloisomerization methodology has been reported. The capability of gold(III) chloride to promote cycloisomerization of both α, β-acetylenic oximes and α, β-acetylenic hydrazones is the centrepiece of the strategy. A range of acetylenic precursors were investigated to afford 28 examples of the products with good to excellent chemical yields. Selected compounds were screened for their cytotoxic potential towards COLO320 cancer cell lines. The IC50 values of the tested compounds were in the micromolar range, with the best compound, 5-(6-Methoxy-naphthalen-2-yl)-3-phenyl-isoxazole (3h) displaying an IC50 of 38.9 μM. For this compound, the crystal structure in complex with Aurora-A kinase was obtained which revealed details of its binding mode within the active site with a free energy of binding -9.54 kcal/mol.

The present study was undertaken to investigate the anticancer activity of methyl caffeate isolated from Solanum torvum Swartz. fruit and to explore the molecular mechanisms of action in MCF-7 cells. Cytotoxic properties of hexane, ethyl acetate and methanol extracts were carried out against MCF-7 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Ethyl acetate extract showed good cytototoxic activities compared to hexane and methanol extracts. Methyl caffeate was isolated from the ethyl acetate extract using column chromatography. Cytotoxic properties of methyl caffeate was investigated against MCF-7, A549, COLO320, HepG-2 and Vero cells. The compound showed potent cytotoxic properties against MCF-7 cells compared to A549, COLO320 and HepG-2 cells. Methyl caffeate significantly reduced cell proliferation and increased formation of fragmented DNA and apoptotic body in MCF-7 cells. Bcl-2, Bax, Bid, p53, caspase-3, PARP and cytochrome c release were detected by western blot analysis. The activities of caspases-3 and PARP gradually increased after the addition of isolated compound. Bcl-2 protein was down regulated; Bid and Bax were up regulated after the treatment with methyl caffeate. Molecular docking studies showed that the compound bound stably to the active sites of poly (ADP-ribose) polymerase-1 (PARP1), B cell CLL/lymphoma-2 (BCL-2), E3 ubiquitin-protein ligase (MDM2) and tubulin. The results strongly suggested that methyl caffeate induced apoptosis in MCF-7 cells via caspase activation through cytochrome c release from mitochondria.

Antimicrobial agents 4a–g and 5a–g with very good potency were synthesized with 100% ee from phenylpropanolamine (norephedrine) by BF3 catalyzed three components one pot Mannich reaction in good yields. Obtained compounds were characterized using spectral techniques. Antimicrobial study of these compounds revealed a good to very high potential activity against tested microbes when compared to standard antimicrobial drugs streptomycin and ketoconazole. These synthesized compounds exhibited significant minimum inhibitory concentration (MIC) values against Gram positive and Gram negative bacteria. Amongst compound 4b, 4c, 4d, 4e, 5a, and 5e exhibited very high potent MIC values against tested twelve bacteria and three fungi when compared to control. When subjected to molecular docking, in silico studies revealed significant binding energies ranging from −7.06 to −8.90 kcal/mol for all obtained compounds towards target receptor DNA topoisomerase IV and amongst compounds 4b and 4d have shown maximum binding energies 8.70 and 8.90 kcal/mol, respectively.

A series of N-substituted isatin thiosemicarbazone ligands (L1–L5) and their nickel(II) complexes [Ni(L)2] (1–5) were synthesized and characterized by elemental analyses and UV-Visible, FT-IR, 1H & 13C NMR, and mass spectroscopic techniques. The molecular structure of the ligands (L1 and L2) and complex 1 was confirmed by single crystal X-ray crystallography. The single crystal X-ray structure of 1 showed distorted octahedral geometry. The interaction of calf thymus (CT) DNA and bovine serum albumin (BSA) with the nickel(II) complexes was explored using absorption and emission spectral methods. A DNA cleavage study showed that the complexes cleaved DNA without any external agents. The alterations in the secondary structure of the protein by the nickel(II) complexes (1–5) were confirmed by synchronous and three dimensional fluorescence spectroscopic studies. The interaction of the complexes with DNA/protein also has been supported by molecular docking studies. An in vitro cytotoxicity study of the complexes found significant activity against human breast (MCF7) and lung (A549) cancer cell lines, with the best results for complexes 4 and 2 respectively, where the IC50 value is less than 0.1 μM concentration.

An efficient diversity oriented synthesis of [1,2,3]triazolo[1,5-a][1,4]benzodiazepines has been developed by sequential diazotization, azidation and cycloaddition reactions in a one-pot fashion. This strategy allows an easy accessibility of triazole fused [1,4]benzodiazepines in good yields. The main objective of this methodology is to introduce various substituents at all possible positions under mild reaction conditions. All the synthesized compounds were evaluated for their antimicrobial, anticancer and in silico activity. Among the tested compounds (2a–n), the derivatives 2a, 2b, 2d, 2k, 2g, 2j, 2m and 2l have displayed a broad spectrum of antibacterial activity. Anticancer activity results revealed that compounds 2a, 2g and 2m exhibited potent in vitro anticancer activity against A549 lung adenocarcinoma cancer cell line. Further, molecular docking studies of all the synthesized compounds were performed to gain a comprehensive understanding of the plausible binding modes and also to compare the theoretical and experimental results of these compounds.

Novel 1,4-disubstituted 1,2,3-triazolo bosentan derivatives 1a–n from bosentan 2 were synthesized in good yields by sequential chlorination, azidation followed by Cu(I) catalyzed 1,3-dipolar cycloaddition. All obtained compounds 1a–n were evaluated for their antimicrobial and in vitro anticancer activities and by in silico docking studies. Among all tested compounds 1e,f and 1h–j show better antimicrobial activities against the tested bacteria and fungi. When subjected to anticancer testing, compounds 1g–j and 1n show significant activities against both A549 and SKOV-3 cell lines with IC50 values at 7.81 μg mL−1 and among them compound 1i exhibited very potent activity. In addition, no toxicity was calculated up to 2 mg mL−1 in Vero cells. In silico studies were conducted to investigate the possible bonding modes of 1a–n with target receptors namely DNA topoisomerase IV (4 EMV) and anaplastic lymphoma kinase (2XP2). Among them, compounds 1e and 1h show maximum binding energies with 4EMV and 2XP2 receptors, respectively which also exhibited good antimicrobial and potent anticancer activities.

The asymmetric unit of the title compound, C24H18N2O, comprises two crystallographically independent molecules (AandB), with slightly different conformations. In each molecule, there is an intramolecular C—H...O hydrogen bond forming anS(6) ring motif. The pyridazine rings of the pyrazolo[1,2-a]cinnoline units have screw-boat conformations. Their mean planes are inclined to the phenyl rings by 83.81 (8) and 74.19 (8)° in moleculeA, and 89.72 (8) and 71.07 (8)° in moleculeB. In the crystal, theAandBmolecules are linked by a pair of C—H...O hydrogen bonds, forming an A–B dimer with anR22(14) ring motif. These dimers are linked by further C—H...O hydrogen bonds, forming ribbons propagating along theb-axis direction. The ribbons are linked by a number of C—H...π interactions, forming a three-dimensional structure.

In the title compound, C23H18O5, the two methoxy-substituted benzene rings are inclined to one another by 67.0 (2)° and to the mean plane of the 1H-isochromene ring system by 67.21 (16) and 27.61 (17)°. There is an intramolecular C—H...π interaction present involving the two 4-methoxyphenyl rings. In the crystal, molecules are linked by O—H...O hydrogen bonds, forming chains propagating along the [301] direction. The chains are linked by a number of C—H...π interactions, forming a three-dimensional structure.

The research examines the drivers and shared preferences of consumers towards adopting the mobile payment systems in the Indian context. A survey was conducted with 152 respondents in the Coimbatore City, State of Tamil Nadu, India. A structured questionnaire was developed using the technology acceptance model (TAM) framework constructs. The multivariate tools like factor analysis and cluster analysis were used for data analysis. The results reveal that perceived usefulness and ease of using mobile payments primarily drive the preferences of consumers. The common preferences among users and non-users of mobile payment services were classified and analysed. The insights from the classification have managerial implications, and the paper discusses them in detail.

Currently Streptomyces is one of the most important antibiotic producing microorganisms against several diseases. In the present study Streptomyces olivochromogenes ERINLG-261 was isolated from the soil samples of the Mudumalai hills, Western Ghats, India. Morphological, physiological, biochemical and 16S rRNA studies strongly suggested that this isolate belonged to the genus Streptomyces. ERINLG-261 showed good antimicrobial activity against different bacteria and fungi in Micromonospora fermentation medium. The active ethyl acetate extract was packed in column chromatography over silica gel which led to the isolation of 2-hydroxy-9,10-anthraquinone as the active principle. The isolated compound showed good antimicrobial activity against tested bacteria and fungi in minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) studies. The compound showed moderate in vitro antiproliferative activity against A549 and COLO320 cells. The compound was subjected to molecular docking studies for the inhibition of Topoisomerase, TtgR and Beta-lactamase enzymes which are targets for antimicrobials. Docking results of the compound showed low docking energy with these enzymes indicating its usefulness as antimicrobial agent. This is the first report of antimicrobial and antiproliferative activity of 2-hydroxy-9,10-anthraquinone isolated from Streptomyces olivochromogenes along with molecular docking studies. Keywords: Streptomyces olivochromogenes, Antimicrobial, Cytotoxic, Molecular docking, 2-Hydroxy-9,10-anthraquinone

Among the title isoxazoles (II) and pyrazoles (IV), compound (IIi) shows the highest cytotoxic potential towards the COLO320 cancer cell lines.

Rhodium catalysed dehydrogenative C–H/N–H functionalization was developed to construct phthalazino[2,3-a]-/indazolo[1,2-a]cinnolines by reacting N-phenyl phthalazine/indazole with alkynes. The synthesized compounds exhibit prominent fluorescence properties in solid and aggregation states. Their application in cell imaging was investigated using various cancer cell lines.

Antimicrobial agents 4a–g and 5a–g with very good potency were synthesized with 100% ee from phenylpropanolamine (norephedrine) by BF3 catalyzed three components one pot Mannich reaction in good yields. Obtained compounds were characterized using spectral techniques. Antimicrobial study of these compounds revealed a good to very high potential activity against tested microbes when compared to standard antimicrobial drugs streptomycin and ketoconazole. These synthesized compounds exhibited significant minimum inhibitory concentration (MIC) values against Gram positive and Gram negative bacteria. Amongst compound 4b, 4c, 4d, 4e, 5a, and 5e exhibited very high potent MIC values against tested twelve bacteria and three fungi when compared to control. When subjected to molecular docking, in silico studies revealed significant binding energies ranging from −7.06 to −8.90 kcal/mol for all obtained compounds towards target receptor DNA topoisomerase IV and amongst compounds 4b and 4d have shown maximum binding energies 8.70 and 8.90 kcal/mol, respectively.

An efficient diversity oriented synthesis of [1,2,3]triazolo[1,5-a][1,4]benzodiazepines has been developed by sequential diazotization, azidation and cycloaddition reactions in a one-pot fashion. This strategy allows an easy accessibility of triazole fused [1,4]benzodiazepines in good yields. The main objective of this methodology is to introduce various substituents at all possible positions under mild reaction conditions. All the synthesized compounds were evaluated for their antimicrobial, anticancer and in silico activity. Among the tested compounds (2a–n), the derivatives 2a, 2b, 2d, 2k, 2g, 2j, 2m and 2l have displayed a broad spectrum of antibacterial activity. Anticancer activity results revealed that compounds 2a, 2g and 2m exhibited potent in vitro anticancer activity against A549 lung adenocarcinoma cancer cell line. Further, molecular docking studies of all the synthesized compounds were performed to gain a comprehensive understanding of the plausible binding modes and also to compare the theoretical and experimental results of these compounds.

The present study investigated the anticancer activity of 2,3-dihydroxy-9,10-anthraquinone against different cancer cells such as MCF-7, COLO320, HepG-2, Skov-3, MOLM-14, NB-4, CEM, K562, Jurkat, HL-60, U937, IM-9 and Vero. 2,3-dihydroxy-9,10-anthraquinone showed good antiproliferative activity against COLO320 cells when compared to other tested cells. The cytotoxicity results showed 79.8% activity at the dose of 2.07 μM with IC50 value of 0.13 μM at 24 h in COLO320 cells. So we chose COLO320 cells for further anticancer studies. mRNA expression was confirmed by qPCR analysis using SYBR green method. Treatment with 2,3-dihydroxy-9,10-anthraquinone was found to trigger intrinsic apoptotic pathway as indicated by down regulation of Bcl-2, Bcl-xl; up regulation of Bim, Bax, Bad; release of cytochrome c and pro-caspases cleaving to caspases. Furthermore, 2,3-dihydroxy-9,10-anthraquinone stopped at G0/G1 phase with modulation in protein levels of cyclins. On the other hand PI3K/AKT signaling plays an important role in cell metabolism. We found that 2,3-dihydroxy-9,10-anthraquinone inhibits PI3K/AKT activity after treatment. Also, COX-2 enzyme plays a major role in colorectal cancer. Our results showed that the treatment significantly reduced COX-2 enzyme in COLO320 cells. These results indicated antiproliferative activity of 2,3-dihydroxy-9,10-anthraquinone involving apoptotic pathways, mitochondrial functions, cell cycle checkpoint and controlling the over expression genes during the colorectal cancer. Molecular docking studies showed that the compound bound stably to the active sites of Bcl-2, COX-2, PI3K and AKT. This is the first report of anticancer mechanism involving 2,3-dihydroxy-9,10-anthraquinone in COLO320 cells. The present results might provide helpful suggestions for the design of antitumor drugs toward colorectal cancer treatment.

Antimicrobial agents 4a-g and 5a-g with very good potency were synthesized with 100% ee from phenylpropanolamine (norephedrine) by BF3 catalyzed three components one pot Mannich reaction in good yields. Obtained compounds were characterized using spectral techniques. Antimicrobial study of these compounds revealed a good to very high potential activity against tested microbes when compared to standard antimicrobial drugs streptomycin and ketoconazole. These synthesized compounds exhibited significant minimum inhibitory concentration (MIC) values against Gram positive and Gram negative bacteria. Amongst compound 4b, 4c, 4d, 4e, 5a, and 5e exhibited very high potent MIC values against tested twelve bacteria and three fungi when compared to control. When subjected to molecular docking, in silico studies revealed significant binding energies ranging from -7.06 to -8.90 kcal/mol for all obtained compounds towards target receptor DNA topoisomerase IV and amongst compounds 4b and 4d have shown maximum binding energies 8.70 and 8.90 kcal/mol, respectively.

Vilsmeier–Haack reactions (VHR) with acetanilides afforded 2-chloro 3-formyl quinoline derivatives. The reactions obeyed second order kinetics with a first order dependence on VHR as well as acetanilide. Significant rate enhancements were observed when transition metal ions such as Cu(II), Ni(II), Co(II), and Cd(II) were used as catalysts in these reactions. The kinetic results in transition metal ion catalyzed reactions coupled with uv-visible spectrophotometric observations substantiated the participation of mixed ligand precursors of the type [M(II)S(VHR)] involving acetanilides and VH reagents in the rate limiting step. Activation parameters were computed and interpreted suitably.