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A series of new 4-chloro-3-nitrobenzene sulfonamide derivatives 3(a-j) were synthesized from 4-chloro-3-nitrobenzene sulfonyl chloride by reacting various amino acid esters and amines 2(a-j) in high yields. The structures of all the synthesized compounds were characterized by the IR, NMR (1H & 13C), mass and elemental analyses. Further, all the synthesized compounds were tested for the antimicrobial activity and docking studies were carried out with DNA Gyrase-A. Most of the compounds showed good to moderate antimicrobial activities and binding affinity towards DNA Gyrase-A structure.

Different kinds of secondary metabolites present in the medicinal plants play an important role to alleviate different human ailments including neurodegenerative disorders such as Parkinson's, Alzheimer's, epilepsy and schizophrenia etc. Recently we have isolated and characterized a novel bioactive compound viz. 3-(3,4-dimethoxy phenyl)-1-4(methoxy phenyl)prop-2-en-1-one from the methanolic extract of Celastrus paniculatus (CP) which has been widely used for the treatment of neurodegenerative diseases. The present investigation is mainly aimed to evaluate the neuroprotective potential of the above bioactive compound against ketamine-induced schizophrenia with particular reference to catecholaminergic metabolism using in vivo and in silico methods. Ketamine-induced schizophrenia caused significant elevation in biogenic amines (epinephrine, nor epinephrine, dopamine and 5-HT) and monoamine oxidase activity levels which were restored to normal during the treatment with the bioactive compound akin to the reference compound, clozapine. In addition, the compound has shown highest binding score against all the biogenic amine receptors viz. D1, D2, D3, D4 and serotonin receptor, 5-HT2A with lowest inhibition constant values than the reference compound, clozapine. The present findings suggest that modulation of CNS monoamine neurotransmitter system might partly contribute to the impairments associated with schizophrenia and the plant compound alleviates the monoaminergic abnormalities associated with the neurological dysfunction.Communicated by Ramaswamy H. Sarma.

Outstanding increase of oral absorption, bioavailability, and antiviral efficacy of phosphorylated nucleosides and basic antiviral influence of abacavir is the central idea for the development of n...

This study reports the design and synthesis of novel dialkyl (4-amino-5H-chromeno[2,3-d]pyrimidin-5-yl)phosphonates as potential antitumor agents against A549 (lung cancer), DU-145 (prostate cancer), PC-3 (prostate cancer), HeLa (cervical cancer) and MCF-7 (breast cancer), cell lines evidenced from the in vitro antitumor studies performed by MTT assay (across 10-30 μM concentrations). The structural eminence of these synthesized molecules has emanated by designing the structural core by uniting the chromene, pyrimidine and phosphonate moieties into one, which has augmented their novelty and made them unreported. Further the deep structural activity relationship study investigations articulated that the title compounds are promising drug-like compounds and potential inhibitor of histidine amino acid residue present on the respective enzymatic proteins [3QJZ (A549), 3VHE (DU-145), 3V49 (PC-3), 3F81 (HeLa),amp; 3R7Q (MCF-7)] of the cell lines screened and are identified as responsible for the multi-faceted antitumor activities predicted in vitro. The obtained results were further supported by molecular docking studies, QSAR, ADMET, and bioactivity studies which have supported them as potential BBB penetrable molecules and proficient CNS active neuro-protective agents during drug delivery.

In the present study, a new series of (bis)ureas 11(a–f) and (bis)thioureas 13(a–f) of 3,3'-dimethoxy-[1,1'-biphenyl]-4,4'-diamine dihydrochloride (9) has been synthesized. This precursor intermediate 9 in high yields was preparedfrom the commercial starting material, 4,4'-dinitro-[1,1'-biphenyl]-3,3'-diol (7) by following the chemical transformations such as methylation of hydroxyl groups and reduction of nitro to an amine functionality. Antimicrobial and antioxidant activities of the synthesized compounds were evaluated to screen for their biological significance. Antimicrobial activity screening results against four bacteria and two fungi unveiled that a few compounds, 11 b/13b, 11e/13e, and 11d (MIC 3.125 − 6.25 µg/ml) against all the tested bacterial strains and compound 11d against Cladosporium species (MIC 3.125 µg/ml) having potential activity. Especially, (bis)urea compounds 11a, 11 b, and 11e, and (bis)thiourea compounds 13a, 13d, and 13f (MIC 3.125 µg/ml) are proved the comparable activity with standard, cefixime (MIC 3.125 µg/ml) against P. aeruginosa. On the other hand, a few compounds 11c/13c, 13d, and 11e/13e were found, by using DPPH and FRAP methods, to exhibit a good antioxidant activity (IC50 range 25.0–32.5 µg/ml). The synthesized compounds were docked well in the active site of an enzyme, DNA Gyrase A, and the predictions of in silico-ADME and pharmacokinetic parameters suggest that the compounds have good oral bioavailability. The results demonstrate that this class of compounds has an expedient scope to use as antibacterial and antioxidant agents upon further development.

Schizophrenia is a devastating illness and displays a wide range of psychotic symptoms. Accumulating evidence indicate impairment of bioenergetic pathways including energy storage and usage...

Synthesis of a series of new urea and thiourea compounds have been accomplished by the reaction of 2,3-dihydro-1H-inden-1-amine with various phenyl isocyanates and isothiocyanates. These compounds were evaluated for their antioxidant activity by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and nitric oxide (NO) radical scavenging assay methods including IC50 values. Some of the compounds exhibited potential activity in the two tested methods. Among the series of compounds, urea derivative linked with 4-bromo phenyl ring (4b), and thiourea derivatives bonded with phenyl ring (4e), 4-fluoro phenyl ring (4f) and 4-nitro pheyl ring (4h) were found to exhibit promising anti oxidant activity with low IC50 values. Where four of the title comounds exhibited higher bindig energies than the reference compound (Imatinib) in in silico molecular docking studies with Aromatase. All the synthesized compounds were characterized by IR, 1H, 13C NMR and mass spectral data.

A simple method was employed for the synthesis of dihydropyrano[3, 2-b]chromenedione derivatives (4a-o) in high yields by condensation of 5, 5-dimethylcyclohexane-1, 3-dione(1), different aromatic aldehydes (2a-o), and 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one(3), using meglumine as a stable and reusable catalyst. Meglumine, an amino sugar, was employed as an environmentally benign catalyst, due to its splendid properties such as being inexpensive, recyclable, and biodegradable. The accomplished protocol employs low catalyst loading and easy work-up for the synthesis of 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one derivatives. A great asset is that without any significant loss, the catalyst could be recovered and reused for extended synthetic steps. This offer huge advantage to overcome recyclability issues. Our synthesized compounds were analyzed by IR, 1H, 13C NMR, mass spectra and evaluated for their antioxidant properties by 1, 1-diphenyl-2-picryl hydrazyl radical (DPPH), hydrogen peroxide(H2O2), and nitric oxide (NO) scavenging methods. The correlation in exhibition of antioxidant activity was effective at all doses. The binding interactions and molecular docking studies for entitled compounds were studied against 3MNG protein; 4k exhibited marked binding affinity with excellent docking score of −7.6 Kcal/mol and emerged as a lead compound. © 2019 Wiley Periodicals, Inc. Ural Federal University, UrFU The authors G. Sravya and N. Bakthavatchala Reddy are thankful to Ural Federal University, Yekaterinburg, Russia, for postdoctoral fellowship.

Glutamate and dopamine hypotheses are leading theories of the pathophysiology of schizophrenia. Multiple lines of evidence suggest that dopaminergic and glutamatergic dysfunction is an underlying mechanism in schizophrenia. Since currently available antipsychotic drugs have significant untoward side effects, identification of new neuroprotective compounds from the medicinal plants may prove beneficial in neurodegenerative disorders. In our previous investigation we have isolated, characterized and reported a novel bioactive compound viz. 3-(3, 4-dimethoxy phenyl)-1-(4-methoxy phenyl) prop-2-en-1-one from the Celastrus paniculatus (CP) is used for the current clinical intervention of schizophrenia disease. The present study is mainly aimed to evaluate the neuroprotective potential of the above bioactive compound against ketamine-induced schizophrenia with particular reference to glutamate metabolism using in vivo and in silico methods. The decrease in glutamine content and the activity levels of glutamate dehydrogenase, glutamine synthetase, and glutaminase in different regions of the rat brain suggests lowered oxidative deamination and lowered mobilization of glutamate towards glutamine formation during ketamine-induced schizophrenia. Pre-treatment with the plant compound reversed the alterations in glutamate metabolism and restored the normal glutamatergic neurotransmission akin to the reference drug, clozapine. In addition, the compound has shown strong interaction and exhibited the highest binding energies against selected NMDA receptors with the lowest inhibition constant than the reference drug. Recoveries of these parameters during anti-schizophrenic treatment suggest that administration of plant compound might offer neuroprotection by interrupting the pathological cascade of glutamatergic neurotransmission that occurs during schizophrenia.

During the past few years, there has been exponential growth in the field of ethnopharmacology in the treatment of different human ailments, including neurological disorders. In our previous study, we isolated, characterized, and reported a novel bioactive compound with therapeutic efficacy in vivo, which was used in the current study. This study was designed to investigate the pharmacological effect and therapeutic mechanism of the natural plant compound 3-(3,4-dimethoxy phenyl)-1-(4-methoxy phenyl)prop-2-en-1-one against ketamine-induced toxicity in PC 12 cell lines. Cell death was induced in PC 12 cell lines by incubating with ketamine, and the protection offered by the compound at different concentrations was studied during pretreatment. The therapeutic efficacy was screened through MTT assay, LDH assay, DCF-DA assay, clonogenic assay, RT-PCR, and densitometric analysis. The bioactive compound caused a significant elevation in cell viability up to approximately 80%, down-regulation of cell damage, reduction in free radical damage caused by intracellular reactive oxygen species, and up-regulation of cell survival ability, which was dysregulated during ketamine induction. In addition, RT-PCR analysis of DOPA-related genes suggests that the compound exerted significant inhibition in the expression of these genes, which were overexpressed during ketamine induction. The current findings provide new insight into the neuroprotective mediation of bioactive factors as a prospective therapy for neurological disorders.

A green and efficient one-pot has been developed for the synthesis of a series of new diethyl-(((2,3-dihydrobenzo[b][1, 4] dioxin-6yl)amino)(substituted phenyl)methyl) phosphonates (4a-k) by the Kabachinik-Fields reaction of 2,3-dihydrobenzo[b] [1, 4]dioxin-6-amine (1) with various substituted aldehydes (2a-k) and diethyl phosphite (3) using nano ferrite supported glutathione (nano FGT) as catalyst under microwave irradiation and solvent free conditions. The synthesized compounds were evaluated for their antioxidant (DPPH & FRAP) and anti-inflammatory activity studies. Compounds 4b (naphthyl) and 4k (9-anthracenyl) showed highest antioxidant activity than that of standard ascorbic acid in DPPH method. Whereas compounds 4f (3-nitrophenyl), 4h (3-phenoxyphenyl) and 4k (9-anthracenyl) exhibited low IC50 values than that of standard ascorbic acid in and in Ferric Reducing Antioxidant Power (FRAP) studies. Compounds 4a, 4b, 4h, 4i, and 4k have shown strong anti-inflammatory activity against LPS induced cell death in RAW 264.7 cell lines. Molecular docking studies were also carried out against COX-2 showed high binding energies that are in support of their high anti-inflammatory activity. Being the most bioactive compound (4k) stands as promising next future anti-oxidant and anti-inflammatory agent.

Different kinds of secondary metabolites present in the medicinal plants play an important role to alleviate different human ailments including neurodegenerative disorders such as Parkinson's, Alzheimer's, epilepsy and schizophrenia etc. Recently we have isolated and characterized a novel bioactive compound viz. 3-(3,4-dimethoxy phenyl)-1-4(methoxy phenyl)prop-2-en-1-one from the methanolic extract of

In an attempt to find potential neuroprotective agents, a series of novel 3-(1-((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl) methoxyimino) ethyl)-2H-chromen-2-one derivatives 6a–j were synthesized by using “click reaction” and evaluated for their in vitro neuroprotectivity and toxicity against H2O2-induced PC12 cell lines by using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) reduction assay. Most of them exhibited moderate to good activity in which compound 6e was found to have significant protectivity with cell viability of 94.51 ± 0.68% at 50 µg/ml concentration and half-maximal effective concentration (EC50) value of 14.04 µg/ml against injured PC12 cell lines and low toxicity with half-maximal cytotoxic concentration (CC50) value of 544.88 µg/ml. Furthermore, molecular docking was carried out in order to understand plausible binding modes of novel derivatives with the active site of glycogen synthase kinase-3β enzyme, and the results were well complemented by the in vitro neuroprotective results against H2O2-induced PC12 cell lines. Additionally, in silico ADME properties showed drug likeness with good oral absorption and moderate blood–brain barrier permeability. The structures of all the synthesized compounds were confirmed by 1H NMR, 13C NMR, IR and LC–MS analyses.

A series of new urea and thiourea derivatives of 5-hydroxy tryptophan 3a-l was designed and synthesized from 5-hydroxy tryptophan (1) by treating various isocyanates 2a-g and isothiocyanates 2h-l in the presence of triethylamine (TEA) as a base. The antioxidant activities of the newly synthesized compounds were evaluated by using different in vitro assays such as 1, 1-diphenyl-2-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2) and superoxide. The results obtained from the in vitro studies revealed that the compounds 3a, 3g, 3h, and 3l exhibited the significant high content of antioxidant activity. Besides, molecular docking studies indicated that, all the compounds 3a-l have formed higher binding energies with 3MNG protein than the reference compound 1. Among all the synthesized compounds, 3a, 3l, 3g, 3b, 3c and 3h have exhibited the highest dock scores than the rest of the compounds including the reference compound. Hence, it is concluded that the title compounds will open new vistas for the discovery of strong antioxidants and will stand as remarkable antioxidant moieties in future.

An efficient and convenient Meglumine catalyzed procedure for the synthesis of bis(indolyl) methanes at ambient temperature under aqueous conditions in high yields. The catalytic reaction proceeds very smoothly. Clean reaction, ease of product isolation/purification, easily available reactants, metal free and environmentally friendly reaction conditions are the notable advantages of the present methodology. All the entitled compounds were characterized by IR, 1H, 13C NMR, mass spectra and evaluated for their antioxidant (DPPH, H2O2 and NO scavenging methods). They exhibited potent in vitro antioxidant activity dose-dependently. The binding interactions and molecular docking studies for entitled compounds were studied against 3MNG protein. 4d exhibited marked binding affinity with excellent docking score of −7.6 K.cal/mol and emerged as a lead compound.