Biochanin A - A G6PD inhibitor: In silico and in vitro studies in non-small cell lung cancer cells (A549).

Secondary metabolites from medicinal plants have a well-established therapeutic potential, with many of these chemicals having specialized medical uses. Isoflavonoids, a type of secondary metabolite, have little cytotoxicity against healthy human cells, making them interesting candidates for cancer treatment. Extensive research has been conducted to investigate the chemo-preventive benefits of flavonoids in treating various cancers. Biochanin A (BA), an isoflavonoid abundant in plants such as red clover, soy, peanuts, and chickpeas, was the subject of our present study. This study aimed to determine how BA affected glucose-6-phosphate dehydrogenase (G6PD) in human lung cancer cells. The study provides meaningful insight and a significant impact of BA on the association between metastasis, inflammation, and G6PD inhibition in A549 cells. Comprehensive in vitro tests revealed that BA has anti-inflammatory effects. Molecular docking experiments shed light on BA's high binding affinity for the G6PD receptor. BA substantially decreased the expression of G6PD and other inflammatory and metastasis-related markers. In conclusion, our findings highlight the potential of BA as a therapeutic agent in cancer treatment, specifically by targeting G6PD and related pathways. BA's varied effects, which range from anti-inflammatory capabilities to metastasis reduction, make it an appealing option for future investigation in the development of new cancer therapeutics.

Isolation, identification, and characterization of α- asarone, from hydromethanolic leaf extract of Acorus calamus L. and its apoptosis-inducing mechanism in A549 cells.

Due to the presence of several active secondary metabolites, the traditional Indian and Chinese medicinal herb Acorus calamus L. has been utilized for both medical and culinary purposes since ancient times. A recent report has underscored the promising cytotoxic effect of A. calamus leaves extract against non-small cell lung cancer A549 cells. Thus, we want to separate the bioactive substance from the hydromethanolic extract of A. calamus leaves in the current investigation. Thin-layer chromatography was used to separate the compounds and different spectroscopic methods (UV, FTIR, NMR, and LCMS/MS) were used for the structure prediction. α-asarone was found to be the main bioactive compound present and it was isolated from A. calamus leaves extract. It exerted a good cytotoxic effect with an IC50 value of 21.43 ± 1.27 µM against A549 cells and IC50 value of 324.12 ± 1.32 µM against WI-38 cells. The induction of apoptosis in A549 cells by α-asarone was reaffirmed by the diverse differential staining methods including DAPI, Acridine Orange/Ethidium Bromide, and Giemsa staining. Additionally, α-asarone induced mitochondrial membrane potential (ΔΨm) dissipation with a concomitant increase in the production of ROS. Furthermore, it also increased expressions of caspase-3, caspase-9, caspase-8, DR4, and DR5 genes in A549 cells. In conclusion, α-asarone-induced apoptotic cell death in non-small lung cancer cells (A549) as a result of loss of mitochondrial function, increased ROS production, subsequent activation of an internal and extrinsic caspase pathway, and altered expression of genes controlling apoptosis. As a whole, α-asarone is a plausible therapeutic agent for managing lung cancer. HIGHLIGHTSIsolation of bioactive compound from hydromethanolic leaves extract of Acorus calamus L. by thin layer chromatography.Structural elucidation of the bioactive compound was carried out using different methods like UV analysis, FTIR, NMR, and LC-MS/MS analysis.A plausible mode of action revealed that α-asarone can induce apoptosis in lung cancer cells (A549).Communicated by Ramaswamy H. Sarma.

Bioaccumulation of arsenic(V) from wastewater by live and dead Spirogyra sp.

Contaminated water with arsenic causes a negative impact on socioeconomic status in the concerned area. Existing methods are not much adequate, efficient, and appropriate. Bioremediation of heavy metals with microalgae seems to be a promising and holistic approach to counter the pre-existing associated with heavy metal toxicity. A pure culture of live and dead Spirogyra sp. was tested for its ability to adsorb arsenic(V) and modeling of experimental data was used to interpret the mechanism of bioaccumulation. Langmuir and Freundlich isotherm models were used to explain the sorption of arsenic. The maximum sorption capacity of live Spirogyra sp. was 315 mg/g and dead Spirogyra sp. was 207 mg/g. Mechanism of bioaccumulation for As(V) ions by live and dead Spirogyra sp. were studied using several advanced techniques including Fourier-transform infrared, fluorescence microscopy, and scanning electron microscope. The study summarizes, bioaccumulation of AsO4 -3 by live and dead cells of Spirogyra sp. seems to be promising. The pseudo-second-order rate equation described better the kinetics of As(V) adsorption with good correlation coefficients. The results suggested that live Spirogyra sp. was more suitable to remove As(V) as compared to dead Spirogyra sp.

Potential of live Spirogyra sp. in the bioaccumulation of copper and nickel ions: A study on suitability and sustainability.

AIM: Various industrial and municipal wastes are the major sources of heavy metal contamination in water causing significant environmental issues. Bioremediation is an effective and affordable solution for the removal of metals and metal pollutants from industrial wastewater. This study aimed to assess the efficacy of live and dead Spirogyra sp. for sorption of metals like of Cu2+ and Ni2+ . METHODS AND RESULTS: The live Spirogyra sp. was used for the uptake of Cu2+ and Ni2+ from their aqueous solutions. The equilibrium data were fitted using a Langmuir and Freundlich isotherm model; the maximum uptakes for Cu2+ and Ni2+ were 29 and 521 mg g-1 , respectively. Scanning electron microscopic (SEM) and infrared (IR) spectroscopic studies of Spirogyra sp. and treated Spirogyra sp. with specific metal ions were used to assess the bonding site and extent of sorption mechanism. CONCLUSION: The initial study showed that this biomass takes up a significant amount of metal ions. Compared to the Langmuir model, the Freundlich model showed better sorption process. The pseudo-second-order rate model represented an enhanced kinetics of metal ion adsorption using live Spirogyra sp. SIGNIFICANCE AND IMPACT OF THE STUDY: As bioaccumulation technology is environmental friendly and potentially cost-effective, live Spirogyra sp. is expected to be a good candidate for managing industrial wastewater.

Arylidene analogues as selective COX-2 inhibitors: synthesis, characterization, in silico and in vitro studies.

Pyrazole derivatives are known to be as non-steroidal anti-inflammatory drugs (NSAID). Celecoxib is the pioneer sulfonamide being pyrazole derivative COX-2 inhibitors, which used to treat pain and inflammation; they may also have a role in cancer prevention. In the present investigation, a series of arylidene analogues (NDP-4011 to NDP-4016) were synthesized by the condensation of 4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl) benzenesulfonamide (I) with various substituted aromatic aldehydes in ethanol using a catalytic amount of piperidine. All the synthesized compounds were well characterized by IR, 1H NMR, 13C NMR and mass spectrometry. The cytotoxicity of synthesized compounds was tested on the NRK-52E cell line. From which NDP-4011, NDP-4012, NDP-4013, NDP-1015 and NDP-4016 were found to have higher cytotoxicity whereas NDP-4014 showed less cytotoxicity compared to Celecoxib. The in silico pharmacokinetic parameters of compounds were evaluated to check their candidature as a drug. Molecular docking was carried out on COX-2 structures, which revealed that NDP-4011 to NDP-4016 targets allosteric binding site similar to the binding mode of the selective COX inhibitor Celecoxib. Furthermore, results of in vitro COX-2 inhibition assay supports arylidene analogues as COX-2 inhibitors.

Benzothiazole analogues: Synthesis, characterization, MO calculations with PM6 and DFT, in silico studies and in vitro antimalarial as DHFR inhibitors and antimicrobial activities.

Benzothiazole analogues are of interest due to their potential activity against malarial and microbial infections. In search of suitable antimicrobial and antimalarial agents, we report here the synthesis, characterization and biological activities of benzothiazole analogues (J 1-J 10). The molecules were characterized by IR, Mass, 1H NMR, 13C NMR and elemental analysis. The in vitro antimicrobial activity was investigated against pathogenic strains; the results were explained with the help of DFT and PM6 molecular orbital calculations. In vitro cytotoxicity and genotoxicity of the molecules were studied against S. pombe cells. In vitro antimalarial activity was studied. The active compounds J 1, J 2, J 3, J 5 and J 6 were further evaluated for enzyme inhibition efficacy against the receptor Pf-DHFR, computational and in vitro studies were carried out to examine their candidatures as lead dihydrofolate reductase inhibitors.

1,2,4-Triazole and 1,3,4-oxadiazole analogues: Synthesis, MO studies, in silico molecular docking studies, antimalarial as DHFR inhibitor and antimicrobial activities.

1,2,4-Triazole and 1,3,4-oxadiazole analogues are of interest due to their potential activity against microbial and malarial infections. In search of suitable antimicrobial and antimalarial compounds, we report here the synthesis, characterization and biological activities of 1,2,4-triazole and 1,3,4-oxadiazole analogues (SS 1-SS 10). The molecules were characterized by IR, mass, 1H NMR, 13C NMR and elemental analysis. The in vitro antimicrobial activity was investigated against pathogenic strains, the results were explained with the help of DFT and PM6 molecular orbital calculations. In vitro cytotoxicity and genotoxicity of the molecules were studied against S. pombe cells. In vitro antimalarial activity was studied. The active compounds were further evaluated for enzyme inhibition efficacy against the receptor Pf-DHFR computationally as well as in vitro to prove their candidature as lead dihydrofolate reductase inhibitors.

Phytol induces ROS mediated apoptosis by induction of caspase 9 and 3 through activation of TRAIL, FAS and TNF receptors and inhibits tumor progression factor Glucose 6 phosphate dehydrogenase in lung carcinoma cell line (A549).

A number of drugs as well as lead molecules are isolated from natural sources. Phytol is one of such lead molecule belongs to terpenes group distributed widely in medicinal plants. In the present work, we investigated the cytotoxic behavior of phytol on human lung carcinoma cells (A549). Phytol was found to cause characteristic apoptotic morphological changes and generation of ROS in A549 cells. The mechanism of phytol involved the activation of TRAIL, FAS and TNF-α receptors along with caspase 9 and 3. In silico molecular docking studies revealed that phytol has a good binding affinity with glucose-6-phosphate dehydrogenase (G6PD), which is known to promote tumor proliferation. The ability of phytol to become potential drug candidate has been revealed from the pharmacokinetic study performed in the present study.

Synthesis and biological screening of novel 2-morpholinoquinoline nucleus clubbed with 1,2,4-oxadiazole motifs.

Novel series of 2-morpholinoquinoline scaffolds (6a-n), containing the 1,2,4-oxadiazole and moiety, was designed and synthesized in good yield (76-86%). The synthesized compounds were screened for their preliminary in vitro antimicrobial activity against a panel of pathogenic strains of bacteria and fungi. Molecular docking and pharmacokinetic study were carried out for the prepared compounds. The cytotoxicity of the synthesized compounds was tested at different concentrations using bioassay of S. pombe cells at the cellular level. The effect of synthesized compounds on the DNA integrity of S. pombe was observed on agarose gel. Compounds 6d, 6e, 6g, 6h, 6j and 6n exhibited excellent antimicrobial potency as compared to the standard drugs (i.e Ampicillin, Norfloxacin, Chloramphenicol, Ciprofloxacin). Compounds 6d, 6e, 6g, 6k and 6n were found to have significant antifungal activity as compared to griseofulvin. Compounds 6f, 6i, 6k, 6l were found very less cytotoxic, while compounds 6d, 6e, 6g, 6h were found to exhibit maximum toxicity. The rest of the synthesized compounds were found to be moderately toxic.

Synthesis, characterization and in silico designing of diethyl-3-methyl-5-(6-methyl-2-thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxamido) thiophene-2,4-dicarboxylate derivative as anti-proliferative and anti-microbial agents.

A series of eight compounds diethyl-3-methyl-5-(6-methyl-2-thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxamido) thiophene-2,4-dicarboxilate (KM10-17) analogues have been prepared by conventional methods and characterized by IR, Mass, NMR and elemental analysis. In silico docking studies on Human topoisomerase IIbeta (PDB Id: 3QX3) have been performed for all molecules (KM10-17) synthesized. The compounds were tested for in vitro anti-proliferative activity on VERO and 786-O cell lines. Out of all the synthesized compounds, KM11 &KM16 showed moderate activity on both cell lines. In vitro anti-microbial activity was also checked against Bacillus subtilis (BS), Staphylococcus aurous (SA), Pseudomonas aeruginosa (PA), Escherichia coli (EC) and Candida albicans (CA) by well diffusion method. The compound KM11 was found to have highest zone of inhibition against BS, SA, PA and EC. The molecules KM13 and KM16 exhibited good activity against CA. The compounds KM14 and KM16 indicated good zone of inhibition against BS.

6-Tosyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide analogues: synthesis, characterization, MO calculation, and antibacterial activity.

A series of 6-tosyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide analogues are synthesized by conventional techniques and characterized by elemental analysis, IR, MS, (1)H, and (13)C NMR. These are tested for their antibacterial activity against Bacillus subtilis (abbreviated as BS), Staphylococcus aureus (abbreviated as SA), and Escherichia coli (abbreviated as EC). The synthesized compounds are able to inhibit the growth of the SA and EC. None of the compounds are effective against BS. All valence molecular orbital (abbreviated as MO) calculations with PM6 have been carried out for the molecules for which bioactivity data are available. Ciprofloxacin is taken as the standard antibiotics to compare activity with the molecules synthesized. It has been attempted to correlate the activity of the molecules with their electronic structure.