Induction of pre-chorismate, jasmonate and salicylate pathways by Burkholderia sp. RR18 in peanut seedlings.

AIMS: To characterize the mechanisms by which bacteria in the peanut rhizosphere promote plant growth and suppress Aspergillus niger, the fungus that causes collar rot of peanut. METHODS AND RESULTS: In all, 131 isolates cultured from the peanut rhizosphere were assayed for growth promotion in a seedling germination assay. The most effective isolate, RR18, was identified as Burkholderia sp. by 16S sequencing analysis. RR18 reduced collar rot disease incidence and increased the germination rate and biomass of peanut seeds, and had broad-spectrum antifungal activity. Quantitative analyses showed that RR18 induced long-lasting accumulation of jasmonic acid, salicylic acid and phenols, and triggered the activity of six defence enzymes related to these changes. Comparative proteomic analysis of treated and untreated seedlings revealed a clear induction of four abundant proteins, including a member of the pre-chorismate pathway, a regulator of clathrin-coated vesicles, a transcription factor and a hypothetical protein. CONCLUSION: Burkholderia sp. RR18 promotes peanut growth and disease resistance, and stably induces two distinct defence pathways associated with systemic resistance. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates that a strain of the Burkholderia cepacia complex can elicit both salicylic- and jasmonic-acid-mediated defences, in addition to having numerous other beneficial properties.

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.

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.

Bacillus species (BT42) isolated from Coffea arabica L. rhizosphere antagonizes Colletotrichum gloeosporioides and Fusarium oxysporum and also exhibits multiple plant growth promoting activity.

BACKGROUND: Colletotrichum and Fusarium species are among pathogenic fungi widely affecting Coffea arabica L., resulting in major yield loss. In the present study, we aimed to isolate bacteria from root rhizosphere of the same plant that is capable of antagonizing Colletotrichum gloeosporioides and Fusarium oxysporum as well as promotes plant growth. RESULTS: A total of 42 Bacillus species were isolated, one of the isolates named BT42 showed maximum radial mycelial growth inhibition against Colletotrichum gloeosporioides (78%) and Fusarium oxysporum (86%). BT42 increased germination of Coffee arabica L. seeds by 38.89%, decreased disease incidence due to infection of Colletotrichum gloeosporioides to 2.77% and due to infection of Fusarium oxysporum to 0 (p < 0.001). The isolate BT42 showed multiple growth-promoting traits. The isolate showed maximum similarity with Bacillus amyloliquefaciens. CONCLUSION: Bacillus species (BT42), isolated in the present work was found to be capable of antagonizing the pathogenic effects of Colletotrichum gloeosporioides and Fusarium oxysporum. The mechanism of action of inhibition of the pathogenic fungi found to be synergistic effects of secondary metabolites, lytic enzymes, and siderophores. The major inhibitory secondary metabolite identified as harmine (ß-carboline alkaloids).

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.

Apoptosis induction capability of silver nanoparticles capped with Acorus calamus L. and Dalbergia sissoo Roxb. Ex DC. against lung carcinoma cells.

Silver nanoparticles (AgNPs) were prepared using a one-step reduction of silver nitrate (AgNO3) with sodium borohydride (NaBH4) in the presence of polyvinylpyrrolidone (PVP) as a capping agent. Plant extracts from D. sissoo (DS) and A. calamus L. (AC) leaves were incorporated during the synthesis process. The crystalline nature of the AgNPs was confirmed through X-ray diffraction (XRD), confirming the face-centered cubic structure, with a lattice constant of 4.08 Å and a crystallite size of 18 nm. Field Emission Gun Transmission Electron Microscopy (FEG-TEM) revealed spherical AgNPs (10-20 nm) with evident PVP adsorption, leading to size changes and agglomeration. UV-Vis spectra showed a surface plasmon resonance (SPR) band at 417 nm for AgNPs and a redshift to 420 nm for PVP-coated AgNPs, indicating successful synthesis. Fourier Transform Infrared Spectroscopy (FTIR) identified functional groups and drug-loaded samples exhibited characteristic peaks, confirming effective drug loading. The anti-cancer potential of synthesized NPs was assessed by MTT assay in human adenocarcinoma lung cancer (A549) and lung normal cells (WI-38) cells. IC50 values for all three NPs (AgPVP NPs, DS@AgPVP NPs, and AC@AgPVP NPs) were 41.60 ± 2.35, 14.25 ± 1.85, and 21.75 ± 0.498 µg/ml on A549 cells, and 420.69 ± 2.87, 408.20 ± 3.41, and 391.80 ± 1.55 µg/ml respectively. Furthermore, the NPs generated Reactive Oxygen Species (ROS) and altered the mitochondrial membrane potential (MMP). Differential staining techniques were used to investigate the apoptosis-inducing properties of the three synthesized NPs. The colony formation assay indicated that nanoparticle therapy prevented cancer cell invasion. Finally, Real-Time PCR (RT-PCR) analysis predicted the expression pattern of many apoptosis-related genes (Caspase 3, 9, and 8).

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.

Pristine, Ni- and Zn-Doped CuSe Nanoparticles: An Antimicrobial, Antioxidant, and Cytotoxicity Study.

The strategy of chemical coprecipitation is implemented to synthesize nanoparticles of pristine CuSe, 5 and 10% Ni-doped CuSe, and 5 and 10% Zn-doped CuSe. All of the nanoparticles are found to be near stoichiometric by the evaluation of X-ray energy using electron dispersion spectra, and the elemental mapping shows uniform distribution. By X-ray diffraction examination, all of the nanoparticles are identified as being single-phase and having a hexagonal lattice structure. Field emission microscopy with electrons in both scanning and transmission modes affirmed the spherical configuration of the nanoparticles. The crystalline nature of the nanoparticles is confirmed by the presence of spot patterns observed in the selected area electron diffraction patterns. The observed d value matches well with the d value of the CuSe hexagonal (102) plane. Findings from dynamic light scattering reveal the size distribution of nanoparticles. The nanoparticle's stability is investigated by ζ potential measurements. Pristine and Ni-doped CuSe nanoparticles exhibit ζ potential values in the preliminary stability band of ±10 to ±30 mV, while Zn-doped nanoparticles feature moderate stability levels of ±30 to ±40 mV. The potent antimicrobial effects of synthesized nanoparticles are studied against Staphylococcus aureus, Pseudomonas aeruginosa, Proteus vulgaris, Enterobacter aerogenes, and Escherichia coli bacteria. The 2,2-diphenyl-1-picrylhydrazyl scavenging test is used to investigate the nanoparticle's antioxidant activities. The results showed the highest activity for control (Vitamin C) with an IC50 value of 43.6 µg/mL, while the lowest for Ni-doped CuSe nanoparticles with an IC50 value of 106.2 µg/mL. Brine shrimps are utilized for in vivo cytotoxicity evaluation of the synthesized nanoparticles, which demonstrates that 10% Ni- and 10% Zn-doped CuSe nanoparticles are more damaging on brine shrimp instead on other nanoparticles with a 100% mortality rate. The lung cancer cell line of human (A549) is used to investigate in vitro cytotoxicity. The results indicate that pristine CuSe nanoparticles are more effective in the context of cytotoxicity against the A549 cell lines, possessing an IC50 of 488 µg/mL. The particulars of the outcomes are explained in depth.

1-D MOF [Ag2(C10H10N3O3S)2(C4H8N)2]n: photocatalytic treatment, crystallographic evaluation, ADMET parameters, CT-DNA and anticancer activity.

Newly synthesized dinuclear crystalline polymer, the silver complex of bidentate Sulfamethoxazole (Ag-SMX) in the presence of secondary ligand pyrrolidine has been characterized by elemental, spectral (1H-NMR spectra, FT-IR spectra, UV-Vis spectra.), powder XRD, and single-crystal X-ray diffraction (single-crystal) analysis. The synthesis molecular structure of the dinuclear [Ag2(C10H10N3O3S)2(C4H8N)2]n complex reveals a one-dimensional polymeric chain with seesaw geometry (τ4 = 0.71): two silvers interlink each other by argentophilic interaction with Ag1…Ag2 separation distance of 3.0047(6) Å. The Hirshfeld surfaces (HS) and 2D fingerprint plots were used to examine the interconnects in the crystal packing. Molecule properties including MEP, MPA, HOMO-LUMO energy, and global reactivity descriptor parameters were computed to understand the molecule's stability. From ADMET parameters, human Intestinal Absorbance data revealed that the compound has the potential to be well absorbed, and also Ag-smx complex cannot cross the blood-brain barrier (BBB). The capacity of the silver complex to interact with CtDNA was investigated using absorption spectroscopy and viscosity tests. The interaction between CT-DNA reveals that the Ag-SMX complex exhibits the strongest binding affinity among all known sulfonamide derivatives and their metal complexes. The silver complex has higher inhibitory action than the free SMX ligand, according to data from a panel of gram (+ve) and gram (-ve) organisms' minimum inhibitory concentrations. In vitro cytotoxicity investigation revealed that the IC50 value for Ag-SMX is 57.12 g/mL and for SMX is 100.90 g/mL against human lung cancer cell line (A549). This study revealed that, when compared to SMX free-ligand, Ag-SMX is the most effective in terms of cytotoxicity toward the human lung cancer cell line (A549 cell line). In under 120 min, the synthesized Ag-smx complex showed exceptional photo-degradation characteristics against methylene blue (MB) (10 ppm) in visible light radiation.Communicated by Ramaswamy H. Sarma.

Visible light-driven photocatalysts, quantum chemical calculations, ADMET-SAR parameters, and DNA binding studies of nickel complex of sulfadiazine.

A 3D-supramolecular nickel integrated Ni-SDZ complex was synthesized using sodium salt of sulfadiazine as the ligand and nickel(II) acetate as the metal salt using a condensation process and slow evaporation approach to growing the single crystal. The metal complex was characterized for its composition, functional groups, surface morphology as well as complex 3D structure, by resorting to various analytical techniques. The interacting surface and stability as well as reactivity of the complex were carried out using the DFT platform. From ADMET parameters, human Intestinal Absorbance data revealed that the compound has the potential to be well absorbed, and also Ni-SDZ complex cannot cross the blood-brain barrier (BBB). Additionally, the complex's DNA binding affinity and in-vivo and in-vitro cytotoxic studies were explored utilizing UV-Vis absorbance titration, viscosity measurements, and S. pombe cells and brine shrimp lethality tests. In visible light radiation, the Ni-SDZ complex displayed exceptional photo-degradation characteristics of approximately 70.19% within 70 min against methylene blue (MB).

Synthesis, Spectral Characterization, Thermal Investigation, Computational Studies, Molecular Docking, and In Vitro Biological Activities of a New Schiff Base Derived from 2-Chloro Benzaldehyde and 3,3'-Dimethyl-[1,1'-biphenyl]-4,4'-diamine.

The current research involves the synthesis of a new Schiff base through the reaction between 2-chlorobenzaldehyde and 3,3'-dimethyl-[1,1'-biphenyl]-4,4'-diamine by using a natural acid catalyst and a synthesized compound physicochemically characterized by X-ray diffraction, Fourier transform infrared spectroscopy, 1H- and 13C-nuclear magnetic resonance, and liquid chromatography-mass spectrometry. Thermal studies were conducted using thermogravimetric, differential thermal analysis, and differential thermogravimetric curves. These curves were obtained in an inert nitrogen environment from ambient temperature to 1263 K using heating rates of 10, 15, and 20 K·min-1. Using thermocurve data, model-free isoconversional techniques such as Kissinger-Akahira-Sunose, Flynn-Wall-Ozawa, and Friedman are used to determine kinetic parameters. These parameters include activation energy, phonon frequency factor, activation enthalpy, activation entropy, and Gibb's free energy change. All of the results have been thoroughly investigated. The molecule's anti-inflammatory and antidiabetic properties were also examined. To learn more about the potential of the Schiff base and how successfully it can suppress the amylase enzyme, a molecular docking experiment was also conducted. For in silico research, the Swiss Absorption, Distribution, Metabolism, Excretion, and Toxicity algorithms were used to calculate the theoretical pharmacokinetic properties, oral bioavailability, toxic effects, and biological activities of the synthesized molecule. Moreover, the cytotoxicity tests against a human lung cancer cell line (A549) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay demonstrated that the synthesized Schiff base exhibited significant anticancer properties.

The NLRP3 inflammasome: a potential therapeutic target for traumatic brain injury.

Although the precise mechanisms contributing to secondary brain injury following traumatic brain injury are complex and obscure, a number of studies have demonstrated that inflammatory responses are an obvious and early feature in the pathogenesis of traumatic brain injury. Inflammasomes are multiprotein complexes that prompt the stimulation of caspase-1 and subsequently induce the maturation and secretion of proinflammatory cytokines, such as interleukin-1ß and interleukin-18. These cytokines play a pivotal role in facilitating innate immune responses and inflammation. Among various inflammasome complexes, the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is the best characterized, a crucial role for NLRP3 has been demonstrated in various brain diseases, including traumatic brain injury. Several recent studies have revealed the contribution of NLRP3 inflammasome in identifying cellular damage and stimulating inflammatory responses to aseptic tissue injury after traumatic brain injury. Even more important, blocking or inhibiting the activation of the NLRP3 inflammasome may have substantial potential to salvage tissue damage during traumatic brain injury. In this review, we summarize recently described mechanisms that are involved in the activation and regulation of the NLRP3 inflammasome. Moreover, we review the recent investigations on the contribution of the NLRP3 inflammasome in the pathophysiology of TBI, and current advances and challenges in potential NLRP3-targeted therapies. A significant contribution of NLRP3 inflammasome activation to traumatic brain injury implies that therapeutic approaches focused on targeting specific inflammasome components could significantly improve the traumatic brain injury outcomes.

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.

Biocompatible CuInS2 Nanoparticles as Potential Antimicrobial, Antioxidant, and Cytotoxic Agents.

A simple hydrothermal route is employed to synthesize pure copper indium disulfide (CIS) and CIS nanoparticles (NPs) mediated by various natural plant extracts. The plant extracts used to mediate are Azadirachta indica (neem), Ocimum sanctum (basil), Cocos nucifera (coconut), Aloe vera (aloe), and Curcuma longa (turmeric). The tetragonal unit cell structure of as-synthesized NPs is confirmed by X-ray diffraction. The analysis by energy-dispersive X-rays shows that all the samples are near-stoichiometric. The morphologies of the NPs are confirmed by high-resolution scanning and transmission modes of electron microscopy. The thermal stability of the synthesized NPs is determined by thermogravimetric analysis. The optical energy band gap is determined from the absorption spectra using Tauc's equation. The antimicrobial activity analysis and the estimation of the minimum inhibitory concentration (MIC) value of the samples are performed for Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Enterobacter aerogenes, and Staphylococcus aureus pathogens. It shows that the aloe-mediated CIS NPs possess a broad inhibitory spectrum. The best inhibitory effect is observed against S. aureus, whereas the least effect was exhibited against P. vulgaris. The least MIC value is found for aloe-mediated CIS NPs (0.300 mg/mL) against S. aureus, P. aeruginosa, and E. aerogenes, along with basil-mediated NPs against E. coli. The antioxidant activity study showed that the IC50 value to inhibit the scavenging activity is maximum for the control (vitamin C) and minimum for pure CIS NPs. The in vivo cytotoxicity study using brine shrimp eggs shows that the pure CIS NPs are more lethal to brine shrimp than the natural extract-mediated CIS NPs. The in vitro cytotoxicity study using the human lung carcinoma cell line (A549) shows that the IC50 value of turmeric extract-mediated CIS NPs is minimum (15.62 ± 1.58 µg/mL). This observation reveals that turmeric extract-mediated CIS NPs are the most potent in terms of cytotoxicity toward the A549 cell line.

Conditioned medium from stimulated macrophages inhibits growth but induces an inflammatory phenotype in breast cancer cells.

Disparate roles exist for tumor-associated macrophages in breast cancer growth and progression. The aim of this study was to explore the influence of induced macrophages on the growth of breast cancer cells. THP-1 monocytes were differentiated to macrophages using phorbol 12-myristate 13-acetate. The effect of the medium from THP-1 monocytes or macrophage-conditioned medium (MφCM) on MCF-7 (estrogen receptor and progesterone-positive positive) and MDA-MB-231 (MB; triple-negative) breast cancer cells was determined at 24 h, 48 h and 72 h. Assays were conducted for cell viability, apoptosis, proliferation and cell phenotype, and quantitative real-time polymerase chain reaction (qRT-PCR) for expression of associated genes. MφCM inhibited proliferation of MCF-7 and MB cells in a time-dependent manner and, in particular, decreased viability of MCF-7 cells. MφCM induced a markedly vacuolated phenotype in MCF-7 increased apoptosis in MCF-7 cells, but correlative changes in Bcl-2 or Bax were absent. A multifold and significant reduction in anti-apoptotic Bcl-2 in MB cells was not matched by increased apoptosis. The cell cycle inhibitor CDKN1A was increased in both cell lines, but PCNA decreased only in MB cells. Senescence-associated galactosidase beta-1 (GLB1) mRNA was decreased in MCF-7 cells (48 and 72 h) but increased in MB cells (72 h). Increased expression of interleukin-6 (IL-6) and IL-8 was seen in both cell lines, and increased tumor necrosis factor- α was seen at 24 h for MB and 72 h for MCF-7 indicating increased inflammatory responses of the cancer cells. The two breast cancer celllines had different responses to MφCM, mainly involving inhibition rather than stimulation of growth of the cells, stimulation of senescence (MB cells) and increased inflammatory cytokine expression. The estrogen and progesterone receptor status of the cell lines may determine their response to MφCM. The function of the inflammatory cytokines in breast cancer growth remains to be identified.

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.

Maslinic Acid Inhibits Proliferation of Renal Cell Carcinoma Cell Lines and Suppresses Angiogenesis of Endothelial Cells.

Despite the introduction of many novel therapeutics in clinical practice, metastatic renal cell carcinoma (RCC) remains a treatment-resistant cancer. As red and processed meat are considered risk factors for RCC, and a vegetable-rich diet is thought to reduce this risk, research into plant-based therapeutics may provide valuable complementary or alternative therapeutics for the management of RCC. Herein, we present the antiproliferative and antiangiogenic effects of maslinic acid, which occurs naturally in edible plants, particularly in olive fruits, and also in a variety of medicinal plants. Human RCC cell lines (ACHN, Caki-1, and SN12K1), endothelial cells (human umbilical vein endothelial cell line [HUVEC]), and primary cultures of kidney proximal tubular epithelial cells (PTEC) were treated with maslinic acid. Maslinic acid was relatively less toxic to PTEC when compared with RCC under similar experimental conditions. In RCC cell lines, maslinic acid induced a significant reduction in proliferation, proliferating cell nuclear antigen, and colony formation. In HUVEC, maslinic acid induced a significant reduction in capillary tube formation in vitro and vascular endothelial growth factor. This study provides a rationale for incorporating a maslinic acid-rich diet either to reduce the risk of developing kidney cancer or as an adjunct to existing antiangiogenic therapy to improve efficacy.

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.

Novel morpholinoquinoline nucleus clubbed with pyrazoline scaffolds: Synthesis, antibacterial, antitubercular and antimalarial activities.

A series of novel morpholinoquinoline based conjugates with pyrazoline moiety were synthesized under microwave irradiation. The newly synthesized compounds were screened for their preliminary in vitro antibacterial activity against a panel of pathogenic strains of bacteria and fungi, antituberculosis activity against Mycobacterium tuberculosis H37Rv and antimalarial activity against Plasmodium falciparum. Most of them exhibited significant antibacterial activity as compared to the first line drugs. Compounds 6a and 9d were found to possess excellent antibacterial activity potency as compared to ampicillin (286 µM), chloramphenicol (154 µM) and ciprofloxacin (150 µM). In antifungal screening, against Candida albicans, compounds 6c, 7c, 8a, 8b, 8c and 9b showed significant activity as compared to griseofulvin (1147 µM). Compounds 8b, 6b, 9d, 6a, 9b, 7b and 8a displayed brilliant activity against P. falciparum strain as compared to chloroquine (IC50 0.062 µM) as well as quinine (IC50 0.826 µM). Compounds 6d, 7b, 8b, 9c and 9d exhibited superior antitubercular activity. Among them 8b was found to be equipotent to rifampicin with 95% inhibition. The cytotoxicity of the synthesized compounds was tested using bioassay of Schizosaccharomyces pombe cells at cellular level.