In this work, the biological potency of nitazoxanide (NTZ) was enhanced through coordination with transition metal ions Cu(II), Ni(II), and Zn(II). Initially, complexes with a ligand-metal ...stoichiometry of 2:1 were successfully synthesized and characterized by spectroscopic techniques and thermogravimetric methods. Measurement of the infrared spectrum revealed the bidentate nature of the ligand and excluded the possibility of the metal ion—amide group interaction. Nuclear magnetic resonance spectra showed a reduction in the NH- intensity signal and integration, indicating the possibility of enolization and the formation of keto-enol tautomers. To interpret these results, density functional theory was utilized under B3LYP/6-311G** for the free ligand and B3LYP/LANL2DZ for the metal complexes. We used UV-Vis and fluorescence spectroscopy to understand the biological properties of the complexes. This showed stronger interactions of NTZ-Cu(II) and NTZ-Ni(II) with DNA molecules than the NTZ-Zn(II) compound, with a binding constant (Kb) for the copper complex of 7.00 × 105 M−1. Both Cu(II)- and Ni(II)-NTZ had functional binding to the SARS-CoV-2 (6LU7) protease. Moreover, all metal complexes showed better antioxidation properties than the free ligand, with NTZ-Ni(II) having the best IC50 value of 53.45 μg/mL. NTZ-Ni(II) was an effective antibacterial, with a mean inhibitory concentration of 6 μM, which is close to that of ampicillin (a reference drug). The metal complexes had moderated anticancer potencies, with NTZ-Cu(II) having IC50 values of 24.5 and 21.5 against human breast cancer cells (MCF-7) and cancerous cervical tumor cells (HeLa), respectively. All obtained complexes exhibited high selectivity. Finally, the metal ions showed a practical role in improving the biological effectiveness of NTZ molecules.
Fluxomics is an innovative -omics research field that measures the rates of all intracellular fluxes in the central metabolism of biological systems. Fluxomics gathers data from multiple different ...-omics fields, portraying the whole picture of molecular interactions. Recently, fluxomics has become one of the most relevant approaches to investigate metabolic phenotypes. Metabolic flux using
C-labeled molecules is increasingly used to monitor metabolic pathways, to probe the corresponding gene-RNA and protein-metabolite interaction networks in actual time. Thus, fluxomics reveals the functioning of multi-molecular metabolic pathways and is increasingly applied in biotechnology and pharmacology. Here, we describe the main fluxomics approaches and experimental platforms. Moreover, we summarize recent fluxomic results in different biological systems.
Cancer is a progressive disease of multi-factorial origin that has risen worldwide, probably due to changes in lifestyle, food intake, and environmental changes as some of the reasons. Skin cancer ...can be classified into melanomas from melanocytes and nonmelanoma skin cancer (NMSC) from the epidermally-derived cell. Together it constitutes about 95% of skin cancer. Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC) are creditworthy of 99% of NMSC due to the limited accessibility of conventional formulations in skin cancer cells of having multiple obstacles in treatment reply to this therapeutic regime. Despite this, it often encounters erratic bioavailability and absorption to the target. Nanoparticles developed through nanotechnology platforms could be the better topical skin cancer therapy option. To improve the topical delivery, the nano-sized delivery system is appropriate as it fuses with the cutaneous layer and fluidized membrane; thus, the deeper penetration of therapeutics could be possible to reach the target spot. This review briefly outlooks the various nanoparticle preparations, i.e., liposomes, niosomes, ethosomes, transferosomes, transethosomes, nanoemulsions, and nanoparticles technologies tested into skin cancer and impede their progress tend to concentrate in the skin layers. Nanocarriers have proved that they can considerably boost medication bioavailability, lowering the frequency of dosage and reducing the toxicity associated with high doses of the medication.
(Euphorbiaceae) has been used as an emetic, anthelminthic, and cathartic agent in traditional medicine. We used gas chromatography-mass spectrometry (GC-MS) to characterize the composition of ethyl ...acetate (EAC) and dichloromethane (DCMC) fractions from the whole
plant. EAC and DCMC fractions were evaluated for acetylcholinesterase (AChE) inhibitory activity and acute toxicity. Their effects on intestinal propulsive movement and spasmogenic activity of the gastrointestinal tract (GIT) muscle were also assessed. The compounds detected in both fractions were mostly fatty acids, with about seven compounds in EAC and 10 in DCMC. These included pharmacologically active compounds such as imipramine, used to treat depression, or hexadecanoic acid methyl ester, an antioxidant. Both EAC and DCMC fractions inhibited acetylcholinesterase (AChE) activity with IC
values of 10 µg and 130 µg, respectively. Both the fractions were found to be toxic in a dose-dependent manner, inducing emesis at 0.5 g or higher and lethargy and mortality from 3-5 g upwards. Similarly, both of the fractions showed laxative activity in metronidazole- and loperamide-induced constipation models. EAC relaxed the intestinal muscle at a lower dose (1 mg/mL) than DCMC. Similarly, the EAC extract showed a significant relaxation effect (EC
= 0.67 ± 0.15 mg/mL) on KCL-induced contraction in rabbit jejunum as compared to DCMC (EC
= 5.04 ± 0.05 mg/kg). The present study strongly supports the folklore that this valuable plant is a cathartic agent. Further work is required to isolate and validate the bioactive compounds that act as diarrheal agents in
Lasso peptides are unique in that the tail of the lasso peptide threads through its macrolactam ring. The unusual structure and biological activity of lasso peptides have generated increased interest ...from the scientific community in recent years. Because of this, many new types of lasso peptides have been discovered. These peptides can be synthesized by microorganisms efficiently, and yet, their chemical assembly is challenging. Herein, we investigated the possibility of high pressure inducing the cyclization of linear precursors of lasso peptides. Unlike other molecules like rotaxanes which mechanically interlock at high pressure, the threaded lasso peptides did not form, even at pressures the high pressure up to 14 000 kbar.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Health-care systems that develop rapidly and efficiently may increase the lifespan of humans. Nevertheless, the older population is more fragile, and is at an increased risk of disease development. A ...concurrently growing number of surgeries and transplantations have caused antibiotics to be used much more frequently, and for much longer periods of time, which in turn increases microbial resistance. In 1945, Fleming warned against the abuse of antibiotics in his Nobel lecture: "The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant". After 70 years, we are witnessing the fulfilment of Fleming's prophecy, as more than 700,000 people die each year due to drug-resistant diseases. Naturally occurring antimicrobial peptides protect all living matter against bacteria, and now different peptidomimetic strategies to engineer innovative antibiotics are being developed to defend humans against bacterial infections.
Microbial interactions with plant roots play an imperial role in tomato plant growth and defense against the
Rhizoctonia solani
. This study performed a field experiment with two antagonistic ...bacteria (
Pseudomonas
and
Bacillus
) inoculated in healthy and
Rhizoctonia solani
treated soil in tomato rhizosphere to understand the metabolic pattern and microbial function during plant disease suppression. In the present study, we assessed soil and microbial enzymes, bacterial and fungal cell forming unit (CFU), and carbon utilization profiling through Bio-Eco plates of rhizoplane samples. Antagonist bacteria and pathogen interaction significantly (
p
< 0.05) influenced the bacterial count, soil enzymes (chitinase and glucanase), and bacterial function (siderophore and chitinase production). These results indicated that these variables had an imperial role in disease suppression during plant development. Furthermore, the metabolic profiling showed that carbon source utilization enhanced under fruit development and ripening stages. These results suggested that carbon sources were essential in plant/pathogen/antagonist interaction. Substrates like β-methyl-D-glucoside, D-mannitol, D-galacturonic acid, N-acetyl-D-glucosamine, and phenylethylamine strongly connect with the suppuration of root rot disease. These carbon sources may help to propagate a healthy microbial community to reduce the pathogen invasion in the plant root system, and these carbon sources can be stimulators of antagonists against pathogens in the future.
Abstract Root-knot nematodes (RKNs) are a vital pest that causes significant yield losses and economic damage to potato plants. The use of chemical pesticides to control these nematodes has led to ...environmental concerns and the development of resistance in the nematode populations. Endophytic fungi offer an eco-friendly alternative to control these pests and produce secondary metabolites that have nematicidal activity against RKNs. The objective of this study is to assess the efficacy of Aspergillus flavus (ON146363), an entophyte fungus isolated from Trigonella foenum-graecum seeds, against Meloidogyne incognita in filtered culture broth using GC–MS analysis. Among them, various nematicidal secondary metabolites were produced: Gadoleic acid, Oleic acid di-ethanolamide, Oleic acid, and Palmitic acid. In addition, biochemical compounds such as Gallic acid, Catechin, Protocatechuic acid, Esculatin, Vanillic acid, Pyrocatechol, Coumarine, Cinnamic acid, 4, 3-indol butyl acetic acid and Naphthyl acetic acid by HPLC. The fungus was identified through morphological and molecular analysis, including ITS 1–4 regions of ribosomal DNA. In vitro experiments showed that culture filtrate of A. flavus had a variable effect on reducing the number of egg hatchings and larval mortality, with higher concentrations showing greater efficacy than Abamectin. The fungus inhibited the development and multiplication of M. incognita in potato plants, reducing the number of galls and eggs by 90% and 89%, respectively. A. flavus increased the activity of defense-related enzymes Chitinas, Catalyse, and Peroxidase after 15, 45, and 60 days. Leaching of the concentrated culture significantly reduced the second juveniles’ stage to 97% /250 g soil and decreased the penetration of nematodes into the roots. A. flavus cultural filtrates via soil spraying improved seedling growth and reduced nematode propagation, resulting in systemic resistance to nematode infection. Therefore, A. flavus can be an effective biological control agent for root-knot nematodes in potato plants. This approach provides a sustainable solution for farmers and minimizes the environmental impact.
The seminal discovery of paclitaxel from endophytic fungus
was a milestone in recognizing the immense potential of endophytic fungi as prolific producers of bioactive secondary metabolites of use in ...medicine, agriculture, and food industries. Following the discovery of paclitaxel, the research community has intensified efforts to harness endophytic fungi as putative producers of lead molecules with anticancer, anti-inflammatory, antimicrobial, antioxidant, cardio-protective, and immunomodulatory properties. Endophytic fungi have been a valuable source of bioactive compounds over the last three decades. Compounds such as taxol, podophyllotoxin, huperzine, camptothecin, and resveratrol have been effectively isolated and characterized after extraction from endophytic fungi. These findings have expanded the applications of endophytic fungi in medicine and related fields. In the present review, we systematically compile and analyze several important compounds derived from endophytic fungi, encompassing the period from 2011 to 2022. Our systematic approach focuses on elucidating the origins of endophytic fungi, exploring the structural diversity and biological activities exhibited by these compounds, and giving special emphasis to the pharmacological activities and mechanism of action of certain compounds. We highlight the tremendous potential of endophytic fungi as alternate sources of bioactive metabolites, with implications for combating major global diseases. This underscores the significant role that fungi can play in the discovery and development of novel therapeutic agents that address the challenges posed by prevalent diseases worldwide.
Chrozophora tinctoria is an annual plant of the family Euphorbiaceae, traditionally used as a laxative, a cathartic and an emetic. A methanolic extract of Chrozophora tinctoria (MEC) whole plant and ...an n-butanol fraction of Chrozophora tinctoria (NBFC) were analyzed by gas chromatography–mass spectrometry (GC-MS) to detect the phytochemicals. MEC and NBFC were tested for in vitro anti acetylcholinesterase (AChE) potential. The effect of both samples on intestinal propulsive movement and spasmolytic activity in the gastrointestinal tract (GIT) was also studied. About twelve compounds in MEC and three compounds in NBFC were tentatively identified through GC-MS. Some of them are compounds with known therapeutic activity, such as toluene; imipramine; undecane; 14-methyl-pentadecanoic acid methyl ester; and hexadecanoic acid. Both NBFC and MEC samples were checked for acute toxicity and were found to be highly toxic in a dose-dependent manner, causing diarrhea and emesis at 1 g/kg concentration in pigeons, with the highest lethargy and mortality above 3 g/kg. Both the samples of Chrozophora tinctoria revealed significant (p ≤ 0.01) laxative activity against metronidazole (7 mg/kg) and loperamide hydrochloride (4 mg/kg)-induced constipation. NBFC (81.18 ± 2.5%) and MEC (68.28 ± 2.4%) significantly increased charcoal meal intestinal transit compared to distal water (41.15 ± 4.3%). NBFC exhibited a significant relaxant effect (EC50 = 3.40 ± 0.20 mg/mL) in spontaneous rabbit jejunum as compared to MEC (EC50 = 4.34 ± 0.68 mg/kg). Similarly, the impact of NBFC on KCl-induced contraction was more significant than that of MEC (EC50 values of 7.22 ± 0.06 mg/mL and 7.47 ± 0.57 mg/mL, respectively). The present study scientifically validates the folk use of Chrozophora tinctoria in the management of gastrointestinal diseases such as constipation. Further work is needed to isolate the phytochemicals that act as diarrheal agents in Chrozophora tinctoria.
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