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In the present work, copper oxide nanoparticles have been fabricated by using a biological method. Copper oxide nanoparticles (CuO NPs) have received more attention than other metal oxides due to their distinctive properties and applications. Plant-mediated synthesis of nanoparticles has gained the attention of researchers because of its simple and ecologically sustainable approach. The biosynthesis of CuO NPs included the use of Passiflora edulis leaf extract that acts as a stabilizing and reducing agent. A non-toxic, cost-effective, and ecologically acceptable method was the use of plant leaf extract in the biogenesis of nanoscale materials. UV-vis, SEM, FTIR, and XRD techniques were used to examine the biologically produced copper oxide nanoparticles. The findings of the SEM examination, which gives morphological information, demonstrate that the synthesized NPs have a spherical shape and have an average particle size of between 60 and 65 nm. CuO has been further investigated in the current study as a photo-catalyst in the methylene blue (MB) dye degradation and as an antioxidant in free radical scavenging activities. The decolorization efficiency was approximately 93% after 160 min. Furthermore, CuO nanoparticles were tested for antioxidant performance by scavenging 2, 2-diphenyl-1-picrylhydrazyl hydrate free radicals (DPPH) and evaluated by UV-Vis spectroscopy. The result showed that biologically synthesized CuO NPs can be used as an effective antioxidant. The half maximal inhibitory concentration IC50 of copper oxide nanoparticles was found to be in the range of 0.13–0.20. [ABSTRACT FROM AUTHOR]

The most common reason for fungal infections is the development of Candida yeasts. Candida naturally is occurs on the skin and on most mucosal surfaces. It is proven that 90% of infections are caused by five Candida species: Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei. Herein we've reviewed isolated and fused heterocyclic compounds that exhibit antifungal activity against Candida strains. Over 200 potential fungicidal agents were described, and some of the particularities which affect the action values were determined. Thus, it was noted that the presence of nitro-, methoxy-, trifluoromethyl-, and/or halogenocontaining groups at the specific positions in the benzene ring could significantly increase the inhibition of yeasts growth. That's why using these patterns together with heterocycles while designing target compounds could speed up the search for new antifungal drugs. [ABSTRACT FROM AUTHOR]

Background: Determining the cytotoxicity of test substances is essential for the safety assessment of chemicals. To quantify the cytotoxicity, dose–response curves are determined and the half-maximum inhibitory concentration (IC50) is subsequently calculated. Results often rely on a single endpoint evaluation which typically requires manual sampling and subsequent sample analysis to determine the IC50. Hence, no information on culture behavior are available during treatment. Here, measurement of the oxygen transfer rate (OTR) was applied as a method for time-resolved assessment of the cytotoxicity to (a) provide information on culture behavior during treatment and (b) quantitatively assess the cytotoxic effect of a test substance. Results: To investigate the applicability of the method, different types and concentrations of test substances were added and the OTR was measured for two different CHO suspension cell lines in shake flasks: (a) For CHO cell line one, culture behavior was not affected when 0.1 mM ZnCl2 was added. However, for both cell lines, adding up to 0.2 mM CoCl2 led to a decrease in the OTR that was concentration dependent. For CHO cell line two, adding up to 5% DMSO led to a concentration-dependent decrease in the OTR and in the slope of the OTR; (b) From the measured OTR, dose–response curves were established and used to calculate the IC50. For cell line one, the IC50 for CoCl2 was 0.03 mM while the IC50 from a comparative measurement based on trypan blue exclusion was 0.06 mM. Cell line two was less susceptible to CoCl2 as the IC50 was not reached at the concentrations tested. For DMSO, single OTR values and determined slopes were used for evaluation. In both cases, the IC50 was calculated to 2.3%. Conclusions: Our approach provides a method for analyzing the cytotoxicity of a test substance based on OTR measurements. This method provides (i) insights on culture behavior, (ii) information on the progression of cytotoxicity, (iii) dose–response curves, and (iv) a first indication of IC50 values. Quantitative assessment of cytotoxicity is possible non-invasively and in real-time during treatment. Compared to traditional endpoint evaluation, our method simplifies experimentations and enhances the comparison of assay results. [ABSTRACT FROM AUTHOR]

Copyright of Egyptian Journal of Botany is the property of Egyptian National Agricultural Library (ENAL) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

With a global increase in mortality, particularly in low-income countries, cancer remains one of the most devastating diseases. Medicinal plants rich in phytochemicals have shown promise as chemoprotective and anticancer agents. As a result, in this study, we compiled a list of medicinal plant species that have been used to treat cancer in the last decade. The results of our review show that 170 plant species from 53 plant families have been used to treat various types of cancer. Plant species are categorised based on their taxonomic position and level of cytotoxicity (very strong, strong, cytotoxic, moderate, and weak). The phylogenetic relationships between these plant species were also reconstructed. The most frequently mentioned plant families were Fabaceae, Asteraceae, Solanaceae, Brassicaceae and Polygonaceae. Phytochemicals such as flavonoids, alkaloids, betalains, saponins and polyphenols are found in highly therapeutic plants. The species Solanum , Khaya , Eichhornia , Coccoloba , Annona , Withania , Salicornia , Beta , Persicaria , Persea , Hyphaene and Kalanchoe showed high potency against a range of cancer cells.

Objectives: This study aimed to assess the interaction between metoprolol and Ginkgo tablets during their co-administration to provide a reference for clinical prescribing., Methods: The co-administration of metoprolol (20 mg/kg) and Ginkgo tablets (2.4 mg/kg) was conducted in adult Sprague Dawley (SD) rats (n = 8). An optimized liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the analysis of plasma metoprolol to evaluate its pharmacokinetics. In vitro , the rat liver microsomes were employed to assess the effect of Ginkgo tablets on the metabolic stability of metoprolol and the activity of Cytochrome P450 2D6 (CYP2D6)., Results: The developed LC-MS/MS method was demonstrated of high sensitivity, accuracy, and precision. When co-administered with Ginkgo tablets, it increased the area under the curve (AUC, 59.01 ± 10.11 vs. 39.19 ± 10.21 μg/mL × min), the maximum plasma concentration (C max , 461.72 ± 44.64 vs. 276.35 ± 118.09 ng/mL), and the half-life (t 1/2 , 302.83 ± 91.52 vs. 262.34 ± 111.12 min) of metoprolol in rats and reduced the clearance rate (0.346 ± 0.057 vs. 0.539 ± 0.145 L/min/kg). In vitro , Ginkgo tablets improved the metabolic stability of metoprolol and suppressed the activity of CYP2D6 in a concentration-dependent manner with the IC 50 value of 11.17 μM., Conclusion: Co-administration of metoprolol with Ginkgo tablets resulted in increasing its systemic exposure through inhibiting CYP2D6 activity., Competing Interests: None., (AJTR Copyright © 2024.)

Objective: Breast cancer is the most frequently diagnosed cancer and the second cause of death worldwide. The drug often used for chemotherapy is cisplatin. However, the drug cisplatin has a number of problems, including lack of selectivity, undesirable side effects, resistance, and toxicity in the body. So research is carried out on new drug compounds with low toxicity by designing in silico with molecular docking., Methods: Mn(II) Cysteine-Tyrosine dithiocarbamate is a new complex molecule whose research involves several steps, such as in-silico molecular docking testing with target proteins, ADMET then synthesis, characterization and in-vitro MCF-7 cells for anticancer drugs. The synthesis process involves the reaction of manganese metal with tyrosine, cysteine, CS2 and KOH. Characterization tests have been carried out including FT-IR spectroscopy, SEM-EDS, UV Vis, conductivity, melting point and XRD., Result: Confirm the structure of the compound using UV Vis, obtained orbitals π to π* and n to π* in the group N = C = S is represented by the absorption at 400 nm and 600 nm, FT-IR with the results obtained by the functional groups O-H, N-H, C =N and C=S. In vitro test results showed morphological changes (apoptosis) in MCF-7 cancer cells starting from 250 μg/mL and an IC50 value of 416.90 µg/mL. Molecular docking studies of the Mn(II)Cysteine-Tyrosine dithiocarbamate complex were identified with 4,4',4''-[(2R)-butane-1,1,2-triyl]triphenol - Estrogen α which showed an active site with amino acid residues GLU323, GLU385, VAL446, ILE514, TRP360, LYS449, MET388, MET357, PHE445, VAL392 and ILE389. Hydrophobic and hydrophobic bonds are seen in Mn(II)Cysteine-Tyrosine dithiocarbamate - Estrogen α has a bond energy of -77.5372 kJ/mol., Conclusion: Despite having a high H-bond interaction intensity, the chemical does not have a powerful enough anticancer impact. Despite the produced compound's low bioactivity, this study should offer important new understandings into how molecular structure affects anticancer activity.

Abstract Background Abiotic and biotic stresses induce oxidative processes in plant cells that this process starts with the production of ROSs which cause damage to the proteins. Therefore, plants have increased their antioxidant activity to defend against this oxidative stress to be able to handle stress better. In this research, 14 different tea accessions in a randomized complete block design with two replications were evaluated in two normal and drought stress conditions, and their antioxidant activity was measured by DPPH-free radicals’ assay and gene expression analysis. Results The results of gene expression analysis showed that the 100 and 399 accessions and Bazri cultivar had high values for most of the antioxidant enzymes, ascorbate peroxidase, superoxide dismutase, catalase, and peroxidase under drought stress conditions while the 278 and 276 accessions had the lowest amount of antioxidant enzymes in the same situation. Results showed that the IC50 of the BHT combination was 90.12 μg/ ml. Also, The IC50 of accessions ranged from 218 to 261 μg/ml and 201–264 μg/ml at normal and drought stress conditions, respectively. The 100 and 399 accessions showed the lowest IC50 under normal and drought stress conditions, while 278 and 276 accessions had the highest value for IC50. The antioxidant activity of tea accession extracts under normal conditions was ranged from 25 to 69% for accessions 278 and 100, respectively. While, the antioxidant activities of extracts under drought stress condition was 12 to 83% for accessions 276 and 100, respectively. So, according to the results, 100 and 399 accessions exhibited the least IC50 and more antioxidant activity under drought stress conditions and were identified as stress-tolerant accessions. However, 278 and 276 accessions did not show much antioxidant activity and were recognized as sensitive accessions under drought stress conditions. Conclusions These results demonstrate that total phenol content, antioxidant activity, and the oxygen-scavenging system can be used as a descriptor for identifying drought-tolerant accessions.

Abstract Background Cell lines are often used to assess the resistance of anticancer drugs when in vivo analysis is not possible. However, the process for establishing anti-cancer drug resistance in cell cultures in vitro and the subsequent method of then evaluating resistance are not clearly established. Traditionally, the IC50 is the most commonly used indicator of resistance evaluation but it cannot represent the effectiveness of anti-cancer drugs in a clinical setting and lacks reliability because it is heavily affected by the cell doubling time. Hence, new indicators that can evaluate anti-cancer drug resistance are needed. Methods A novel resistance evaluation methodology was validated in this present study by establishing sunitinib resistance in renal cell carcinoma cells and assessing the cross-resistance of five different anti-cancer drugs. Results It was confirmed in this present study that the IC50 does not reflect the cell proliferation rates in a way that represents anti-cancer drug resistance. An alternative indicator that can also be clinically meaningful when using in vitro cell line systems is GI100. Additionally, the GR100 allows different cell populations to be calibrated on the same basis when multiple experimental results are compared. Conclusion Since the GR100 has properties that indicate the efficiency of anti-cancer drugs, both the efficacy and GR100 of a particular anti-cancer drug can be used to effectively assess the resistance.

This paper presents antimalarial activity of several triphenyltin(IV) aminobenzoate compounds synthesized from the reaction of triphenyltin(IV) hydroxide with 2-, 3-, and 4-aminobenzoic acid. The activity of the compounds as anti-malaria agents was evaluated using Plasmodium falciparum, and demonstrated that the compounds have about the same IC50 with that of chloroquine (2×10−3 μg/mL) applied as the positive control. The result also showed that the Plasmodium is non-resistent to the compounds synthesized, which is the opposite to chloroquine.

Background: Leishmania is a parasitic protozoan that causes severe illness in humans. While pentavalent antimony compounds (Sb Drug) are used as antileishmanic drugs but are linked to limitations and many adverse complications. Objective: Therefore, commitment is still needed to find a new and successful treatment. Material & methods: In this study, the effect of Ag2O, MgO nanoparticles with mean particles size of (12-28)nm and(7-12)nm respectively on Leishmania was evaluated. Viability percentage of promastigotes following the addition of different concentrations of Ag2O, MgO nanoparticles and Sb drugs (25, 50, 100, 200 and 300 μg / ml ) to the parasite culture, assessed using colorimetric ALAMAR stain in (24,48 72)hours. Results: The concentration that the number of parasite by half (IC50) value was measured after 24, 48 and 72 hours for Sb, Ag2O NPs and MgO NPs. For Ag2O NPs the IC50 was 2.404 after 72 hours only, and doesn’t reveal any value in 24 hour, 48 hour, in comparison to Sb drug and MgO NPs which doesn't reveal IC50 value in all used concentration and periods. Conclusion: Our data determine the superiority of Ag2O NPs and MgO NPs over standard in vitro pentostam that's it. Provides the possibility of using these Ag2O NPs and MgO NPs as a drug target for candidates with better antileishmanial efficacy.

Molecular neuroimaging is today considered essential for evaluation of novel CNS drugs; it is used to quantify blood-brain barrier permeability, verify interaction with key target and determine the drug dose resulting in 50% occupancy, IC50. In spite of this, there has been limited data available to inform on how to optimize study designs.Through simulations, we here evaluate how IC50 estimation is affected by the (i) range of drug doses administered, (ii) number of subjects included, and (iii) level of noise in the plasma drug concentration measurements. Receptor occupancy is determined from PET distribution volumes using two different methods: the Lassen plot and Likelihood estimation of occupancy (LEO). We also introduce and evaluate a new likelihood-based estimator for direct estimation of IC50 from PET distribution volumes.For estimation of IC50, we find very limited added benefit in scanning individuals who are given drug doses corresponding to less than 40% receptor occupancy. In the range of typical PET sample sizes (5–20 subjects) each extra individual clearly reduces the error of the IC50 estimate.In all simulations, likelihood-based methods gave more precise IC50 estimates than the Lassen plot; four times the number of subjects were required for the Lassen plot to reach the same IC50 precision as LEO.

The Oxalis corniculata (Oxalidaceae) is one of the most potential medicinal herbs and well known for multiple therapeutic properties (anti-inflammatory, anticancer, antioxidant, antimicrobial, analgesic and diuretic activity). This study investigated phytoconstituents, antibacterial activity and antioxidant activity of Oxalis corniculata leaves extract. Methanol based phytochemical screening of Oxalis corniculata revealed the presence of alkaloids, proteins, phenols, flavonoids, glycosides. The antibacterial activity revealed better potential inhibitory effect against gram-negative bacteria, particularly Escherichia coli and Salmonella typhi compared to Staphylococcus aureus, a gram-positive bacterium. However, 1% methanol extract showed highest antibacterial activity against Escherichia coli followed by Staphylococcus aureus and Salmonella typhi. Antioxidant activity of the methanol extract with 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging showed antioxidant activities with 3.87 µg/mL IC50 value. BIBECHANA 19 (2022) 27-33

Cisplatin is a classic anticancer drug widely used as a reference drug to test new metal complex drug candidates. We found an unexpected diversity in cisplatin-related cytotoxicity values, expressed as IC50 (the half-maximal inhibitory concentration) in tumour cell lines, such as MCF-7, HepG2 and HeLa. We reviewed the data published from 2018 to 2022. A total of 41 articles based on 56 in vitro experiments met our eligibility criteria. Using a meta-analysis based on a random effect model, we evaluated the cytotoxicity of cisplatin (IC50) after 48- or 72-h cell exposure. We found large differences between studies using a particular cell line. According to the random effect model, the 95% confidence intervals for IC50 were extremely wide. The heterogeneity of cisplatin IC50, as measured by the I2 index for all cancer cell lines, was over 99.7% at culture times of 48 or 72 h. Therefore, the variability between studies is due to experimental heterogeneity rather than chance. Despite the higher IC50 values after 48 h than after 72 h, the heterogeneity between the two culture periods did not differ significantly. This indicates that the duration of cultivation is not the main cause of heterogeneity. Therefore, the available data is diverse and not useful as a reference. We discuss possible reasons for the IC50 heterogeneity and advise researchers to conduct preliminary testing before starting experiments and not to solely rely on the published data. We hope that this systematic meta-analysis will provide valuable information for researchers searching for new cancer drugs using cisplatin as a reference drug.

Gap junctions (GJs) made of connexin-43 (Cx43) are necessary for the conduction of electrical impulses in the heart. Modulation of Cx43 GJ activity may be beneficial in the treatment of cardiac arrhythmias and other dysfunctions. The search for novel GJ-modulating agents using molecular docking allows for the accurate prediction of binding affinities of ligands, which, unfortunately, often poorly correlate with their potencies. The objective of this study was to demonstrate that a Quantitative Structure-Activity Relationship (QSAR) model could be used for more precise identification of potent Cx43 GJ inhibitors. Using molecular docking, QSAR, and 3D-QSAR, we evaluated 16 known Cx43 GJ inhibitors, suggested the monocyclic monoterpene d-limonene as a putative Cx43 inhibitor, and tested it experimentally in HeLa cells expressing exogenous Cx43. The predicted concentrations required to produce 50% of the maximal effect (IC50) for each of these compounds were compared with those determined experimentally (pIC50 and eIC50, respectively). The pIC50ies of d-limonene and other Cx43 GJ inhibitors examined by our QSAR and 3D-QSAR models showed a good correlation with their eIC50ies (R = 0.88 and 0.90, respectively) in contrast to pIC50ies obtained from molecular docking (R = 0.78). However, molecular docking suggests that inhibitor potency may depend on their docking conformation on Cx43. Searching for new potent, selective, and specific inhibitors of GJ channels, we propose to perform the primary screening of new putative compounds using the QSAR model, followed by the validation of the most suitable candidates by patch-clamp techniques.

This study investigated the stimulating or inhibitory effect of Zn, Cu, Cd, Pb, and their mixtures on fermentative hydrogen production. Heavy metals inhibited the production process at all concentrations except 0.50 ppm of Zn. Consistent with the half of the maximum inhibitory concentration (IC 50), Cu + Pb caused the greatest inhibition as it is more toxic than other heavy metal mixtures. As the concentration of heavy metal increased, the HBu/HAc ratio (butyrate/acetate) tended to decrease and the amount of hydrogen production decreased. Clostridium sp. , Klebsiella sp. , Dysgonomas sp. , Enterobacter sp. , and other hydrogen-producing bacteria were observed by polymerase chain reaction (PCR) – analysis by denaturing gradient gel electrophoresis (DGGE) during the fermentative hydrogen process. A significant relationship was observed between the richness index and the hydrogen production (p -value = 0.01 < 0.05) from the Pielou index. The Pielou index (E′) and the Shannon-Weaver index (H') had no significant relationship (p -value = 0.12 > 0.05). [Display omitted] • This study investigated the stimulative or inhibitive effects of Zn, Cu, Cd, Pb. • The heavy metals resulted in inhibitory effects at all concentrations except Zn. • Cu + Pb caused the highest inhibition by being more toxic than other mixtures. • Heavy metals with low IC 50 were more sensitive to hydrogen production. • Microbial richness, not diversity, is an important factor for hydrogen production. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a multifactorial global health disorder that is rising at an alarming rate. Cardiovascular diseases, kidney damage and neuropathy are the main cause of high mortality rates among individuals with diabetes. One effective therapeutic approach for controlling hyperglycemia associated with type-2 diabetes is to target alpha-amylase and alpha-glucosidase, enzymes that catalyzes starch hydrolysis in the intestine. At present, approved inhibitors for these enzymes are restricted to acarbose, miglitol and voglibose. Although these inhibitors retard glucose absorption, undesirable gastrointestinal side effects impede their application. Therefore, research efforts continue to seek novel inhibitors with improved efficacy and minimal side effects. Natural products of plant origin have been a valuable source of therapeutic agents with lesser toxicity and side effects. The anti-diabetic potential through alpha-glucosidase inhibition of plant-derived molecules are summarized in this review. Eight molecules (Taxumariene F, Akebonoic acid, Morusin, Rhaponticin, Procyanidin A2, Alaternin, Mulberrofuran K and Psoralidin) were selected as promising drug candidates and their pharmacokinetic properties and toxicity were discussed where available. [ABSTRACT FROM AUTHOR]

Background: Plantainoside D is widely existed in the herbs and possesses various pharmacological activities, making it possible to co-administrate with other herbs. Its effect on cytochrome P450 enzymes (P450) is a risk factor for inducing adverse drug-drug interactions. To assess the effect of plantainoside D on the activity of major P450 isoenzymes in human liver microsomes. Methods: The Cocktail method was conducted in human liver microsomes in the presence of probe substrates. The activity of P450 isoenzymes was evaluated by the production of corresponding metabolites. The concentration-dependent and time-dependent inhibition assays were performed in the presence of 0, 2.5, 5, 10, 25, 50, and 100 μM plantainoside D to characterize the inhibitory effect of plantainoside D. Results: Significant inhibition was observed in the activity of CYP1A2, 2D6, and 3A, which was concentration-dependent with the IC50 values of 12.83, 8.39, and 14.66 μM, respectively. The non-competitive manner and competitive manner were observed in the CYP3A inhibition (Ki = 7.16 μM) and CYP1A2 (Ki = 6.26 μM) and 2D6 inhibition (Ki = 4.54 μM), respectively. Additionally, the inhibition of CYP3A was found to be time-dependent with the KI of 1.28 μM−1 and Kinact of 0.039 min−1. Conclusions: Weak inhibitory effects of plantainoside D on the activity of CYP1A2, 2D6, and 3A were revealed in vitro, implying its potential of inducing interactions with CYP1A2-, 2D6-, and 3A-metabolized drugs. Although further in vivo validations are needed, the feasibility of the Cocktail method in evaluating P450 activity has been verified. [ABSTRACT FROM AUTHOR]

The administration of combinations of drugs is a method widely used in the treatment of different pathologies as it can lead to an increase in the therapeutic effect and a reduction in the dose compared to the administration of single drugs. For these reasons, it is of interest to study combinations of drugs and to determine whether a specific combination has a synergistic, antagonistic or additive effect. Various mathematical models have been developed, which use different methods to evaluate the synergy of a combination of drugs. We have developed an open access and easy to use app that allows different models to be explored and the most fitting to be chosen for the specific experimental data: SiCoDEA (Single and Combined Drug Effect Analysis). Despite the existence of other tools for drug combination analysis, SiCoDEA remains the most complete and flexible since it offers options such as outlier removal or the ability to choose between different models for analysis. SiCoDEA is an easy to use tool for analyzing drug combination data and to have a view of the various steps and offer different results based on the model chosen. [ABSTRACT FROM AUTHOR]

• The paper reviews the antidiabetic potentials of Aloe species. • Aloe vera is the most common species with antidiabetic properties. • Different methods were used to determine their potentials. • Further study is needed to isolate antidiabetic agents from the genus. Of all medicinal plants used to treat ailments, the genus Aloe represents one of the commonest. They manage various pathological conditions, including inflammation, infection, cancer and diabetes mellitus. There are specific reports on the hypoglycemic and antidiabetic potential of different species of Aloe. Still, there is a shortage of comprehensive reports which present all Aloe species with antidiabetic properties. This study aims to integrate available information on all Aloe spp. with antidiabetic potentials. Scientific databases such as PubMed, EBSCOhost, Science Direct, Scopus, and Google Scholar, were utilized to search and collect literature for this review. This review revealed that the most common Aloe sp. with antidiabetic potentials is A. vera. It also showed that few studies were carried out in vitro while most were performed in vivo. We can conclude that Aloe spp. is a potent source of antidiabetic agents. Further studies should be conducted to isolate the antidiabetic compounds from the plant. [ABSTRACT FROM AUTHOR]

In Leishmania sp., the enzymes of de novo cysteine biosynthesis pathway require sulfide. Other organisms utilize sulfide through the sulfide reduction pathway, but Leishmania lacks the gene that encodes these enzymes. Hence, the major source of sulfide for Leishmania is believed to be from the action of 3-mercaptopyruvate sulfurtransferase (3MST) on 3-mercapto-pyruvate (3MP). There has been no effort reported in the past to screen inhibitors against L. donovani 3MST (Ld3MST). As a result, this study examines natural compounds that are potent against Ld3MST and validates it by in vitro activity and cytotoxicity tests. Initially, a library of ~ 5000 natural compounds was subjected to molecular docking approach for screening, and the best hit was validated using a long-term molecular dynamic simulation (MD). Among the docking results, quercetine-3-rutinoside (Rutin) was deemed the best hit. The results of the MD indicated that Rutin was highly capable of interacting with the varied active site segments, possibly blocking substrate access. Additionally, promastigotes and amastigotes were tested for Rutin activity and the IC50 was found to be 40.95 and 90.09 μM, respectively. Similarly, the cytotoxicity assay revealed that Rutin was not toxic even at a concentration of 819.00 μM to THP-1 cell lines. Additionally, the Ld3MST was cloned, purified, and evaluated for enzyme activity in the presence of Rutin. Reduction in the enzyme activity (~ 85%) was observed in the presence of ~ 40 μM Rutin. Thus, this study suggests that Rutin may act as a potent inhibitor of Ld3MST. With further in vivo investigations, Rutin could be a small molecule of choice for combating leishmaniasis. [ABSTRACT FROM AUTHOR]

Copyright of Jornal of Biotechnology Research Center is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Hyperuricemia is a risk factor for gout and other cardiovascular diseases. One of the therapies used is Allopurinol. Unfortunately, it has unwanted side effects. These conditions made researchers continue to seek and develop alternative treatments from natural products. One of which is from plants of the Phyllanthus genus. One of their contents was polyphenols, especially flavonoids. It is an alternative treatment for hyperuricemia because of its minimal side effects. The flavonoids in this genus were reported to have xanthine oxidase inhibitory: quercetin, kaempferol, rutin, apigenin, luteolin, myricetin, catechin, epicatechin, and epigallocatechin with IC50 values from 0.44 M to > 100μM. The presence of π-π interactions between planar rings A and C on flavones with phe 1009 and phe 914 and the addition of hydroxyl groups on flavonoid compounds plays a crucial role in inhibiting xanthine oxidase. [ABSTRACT FROM AUTHOR]

Changes in the osmolality of the extracellular medium (ECM) affect cell volume and cellular processes such as cell migration and proliferation. Not only may high concentrations of zinc (Zn) lead to cell death by apoptosis, but Zn is also a physiological suppressor of apoptosis. The aim of our study was to examine whether Zn and regulation of extracellular osmolality had an effect on the lung cancer cell line (A549) and how to be changed in ECM according to elements and osmolality depending on incubation time and Zn application. Our study consisted of four groups: cell-free medium, ECM of cancer cell after 24 h incubation (24hECM), ECM of cancer cell after 48 h incubation (48hECM), and ECM of cancer cell after 48 h incubation with ZnCl2 (48hECM + Zn). ECM osmolality was measured by using osmometer, and the levels of chromium (Cr), iron (Fe), and magnesium (Mg) elements were analyzed using ICP-OES device for all groups. According to the result of the analysis, a statistically significant difference was found when osmolality and element values of ECM of 24hECM and 48hECM groups were compared with the values of the 48hECM + Zn group. It was observed that there was a decrease in the levels of Cr, Fe, and Mg with Zn application and incubation period in ECM. The regulation of ECM osmolality is a promising method due to biophysical effects on cancer cells. In our study, we speculated that the understanding of the effects of Zn and osmolality with the relationship between ECM and cancer cell might lead to the discovery of biophysical approaches as a novel therapeutic strategy. [ABSTRACT FROM AUTHOR]

Enzyme inhibitor's hydrolyzing carbohydrates, such as α-amylase, play an important role in the control of diabetes mellitus, particularly in patients with type 2 diabetes. In this study, we selected two medicinal plants recommended to treat diabetes in traditional North African medicine: Tetraclinis articulata and Trigonella foenum-graecum. The inhibition kinetics of α-amylase by extracts of these plants was studied by in vitro methods. Enzyme dissociation constants, terminal velocity, and inhibition constants were determined. The results revealed a dose-dependent inhibition of α-amylase with IC50 of 57.74 and 104.93 µg/ml for Trigonella foenum-graecum and Tetraclinis articulata, respectively. The extracts also showed a competitive inhibition of α-amylase by significantly varying the enzymatic dissociation constant from 6.79 mg/ml of the enzyme alone to 27.50 mg/ml with Tetraclinis articulata, and 23.42 mg/ml with Trigonella foenum-graecum. [ABSTRACT FROM AUTHOR]

Cancer is a deadly disease; many treatment strategies are available to cure/treat cancer. After the metal-based anticancer drug (Cisplatin), metal complexes play a vital role in pharmaceutical science. We aimed to analyze the anticancer activity of pyridine Schiff base complexes. This review article searched the anticancer studies of pyridine Schiff base metal complexes from 2015 to 2021. Information was gathered from the selected studies to analyze and highlight the importance of anticancer agents. A total of sixty six full-length articles were collected and evaluated. On the critical assessment, we found that compared to Schiff base ligand, the metal complexes exhibited excellent activity towards various cancer cell lines (including MCF-7, HeLa, HCT-116, Hepa-2). We identified more complexes that exhibited promising activity against various cell lines and revealed IC50 values equal to or even lower than the reference drug used. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is the 3rd most common type of cancer in the world with unsatisfactory therapeutic effectiveness. One of the efforts being made to overcome this problem is by extracting various new chemotherapy agents, including herbal plants. The Nyamplung plant (Calophyllum inophyllum L.) is reported to contain calophyllolide, triterpene, coumarin, saponin, biflavonoids, benzophenones and neoflavanoids which are potential anticancer agents. Objective: This study aims to determine the cytotoxic activity of ethanolic extract of fruit shells and seeds of Nyamplung (Calophyllum inophyllum L.) on WiDr colorectal cancer cells and their selectivity on normal cells (Vero). Methods: The fruit and seeds of Nyamplung were extracted by maceration with 70% ethanol solvent. The cytotoxic test was carried out by the 3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide (MTT) method, with doxorubicin as a positive control. Data analyzed using Microsoft Excel software using linear regression analysis. The IC50 value and selectivity index were used as indicator of toxicity selectivity. Results: The IC50 value of the ethanolic extract of Nyamplung fruit shells on WiDr was 42.47 µg/ml with a selectivity index of 1.50. Meanwhile, the IC50 value of ethanolic extract of Nyamplung seeds was 1,030.41 µg/ml with a selectivity index of 67,982,414.71. Doxorubicin as a positive control obtained IC50 value on WiDr cells of 3.49 µg/ml with a selectivity index of 764.41. Conclusion: The ethanolic extract of Nyamplung seeds was not cytotoxic against WiDr colorectal cancer cells, while the ethanolic extract of Nyamplung fruit sell was moderate cytotoxic with low selectivity index.

مقدمه: ملانوم پوستی به عنوان یکی از مهاجمانه‌ترین انواع سرطان پوست است. این بیماری حدود 75 درصد از کل مرگ و میرهای ناشی از سرطان پوست را تشکیل می‌دهد و تاکنون درمان قطعی برای آن ارائه نشده است. در نتیجه تشخیص به هنگام و جلوگیری از پیشرفت این بیماری حائز اهمیت است. پژوهش‌های زیادی برای یافتن روش‌های درمان و بهبود سرطان ارائه شده است. یکی از جدیدترین روش‌ها در این زمینه استفاده از فناوری نانو برای تشخیص و مهار سلول‌های سرطانی است. در این تحقیق تاثیر استفاده از نانومیکروحباب‌های هوا، اکسیژن و اوزون بر رده سلولی A375 سرطان ملانوما مورد ارزیابی قرار گرفته است.مواد و روش‌ها‌: رده سلولی A375 که با غلظت‎های مختلف نانومیکروحباب‎ها‌ی هوا، اکسیژن و اوزون تیمار شده اند توسط روش MTT مورد ارزیابی قرار گرفته‌اند. به منظور سنجش زنده بودن سلول‌ها، به هر چاهک پلیت ماده MTT اضافه شده و سپس پلیت در انکوباتور قرار گرفته است. یافته‌ها: طبق نتایج این تحقیق کاهش درصد زیست پذیری سلول‌های سرطانی A375 با افزایش غلظت نانومیکروحبابهای اکسیژن و اوزون پس از 24 ساعت نشان دهنده آپوپتوز بوده و مهار چشمگیری بر رشد این سلول‌ها داشته است.نتیجه‌گیری: نتایج حاصل از این تحقیق گویای آن است که نانومیکروحبابهای اکسیژن و اوزون در غلظت‌های بالا باعث مرگ سلولی رده سلول‌های A375 می‌شود. نتایج در این تحقیق کمک خواهد کرد که نقش نانومیکروحباب‌های هوا، اکسیژن و اوزون در درمان سرطان ملانوما بررسی شود.

Preclinical models of tumors have the potential to become valuable tools for commercial drug research and development, and 3D culture systems are gaining traction in this area, particularly in prostate cancer (PCa) research. However, nearly all 3D drug design and screening assessments are based on 2D experiments, suggesting limitations of 3D drug testing. To simulate the natural response of human cells to the drug, we detected the half-maximal inhibitory concentration (IC50) changes of 2D/3D LNCaP cells in the drug docetaxel, as well as the sensitivity of different morphologies of 2D/3D LNCaP to docetaxel treatment. In contrast to 2D LNCaP cells, the evaluation of LNCaP spheroids’ susceptibility to treatment was more complicated; the fitness of IC50 curves of 2D and 3D tumor cell preclinical models differs significantly. IC50 curves were unsuitable for large-sized LNCaP spheroids. More evaluation indexes (such as max inhibition) and experiments (such as spheroids formation) should be explored and performed to evaluate the susceptibility systematically.

Abstract The aim of the current study was to determine the chemical constituents of essential oil and to study the antibacterial and antioxidant activities of essential oil and the extracts obtained from the raw material of Ziziphora wild growing in the floras of Armenia and Artsakh cultivated in the hydroponic conditions. The essential oils were obtained by the method of hydro-distillation. The determination of the essential oil constituents were performed by the GC-MS method. Agar disk diffusion method was used to study the antimicrobial activity of essential oils. The antioxidant activity determination was carried out DPPH test by the spectrophotometric method, at the same time IC50 was determined. The highest values of the essential oils yield (1.25 ± 0.01%) and IC50 13.83±0.218(x10-5)g/l) were received for the plant cultivated in hydroponic conditions. For the first time in the above studied samples, by the method of GC-MS more than 70 components were revealed. The results of the study showed that essential oils of Ziziphora exhibit antimicrobial activity and the extracts revealed relatively expressed antioxidant activity. The study results show the future prospects of the use of Ziziphora not only as the source of flavonoids and essential oils, but also antimicrobial and antioxidant agents.

Natural infections of Plasmodium falciparum, the parasite responsible for the deadliest form of human malaria, often comprise multiple parasite lineages (haplotypes). Multiclonal parasite isolates may exhibit variable phenotypes including different drug susceptibility profiles over time due to the presence of multiple haplotypes. To test this hypothesis, three P. falciparum Cambodian isolates IPC_3445 (MRA-1236), IPC_5202 (MRA-1240) and IPC_6403 (MRA-1285) suspected to be multiclonal were cloned by limiting dilution, and the resulting clones genotyped at 24 highly polymorphic single nucleotide polymorphisms (SNPs). Isolates harbored up to three constituent haplotypes, and exhibited significant variability (p

Many terpyridines and their metal complexes are known to exhibit remarkable potential for the interaction of biological targets. Notably, a subtle change in the structure of the ligand can influence these interactions significantly. In this regard, it would be very interesting to assess the binding affinity of functionalized molecules with DNA/BSA. In this work, a novel ester-based terpyridine (L) and the corresponding four metal complexes with Ni(II) (MC1), Cu(II) (MC2), Fe(III) (MC3) and Ru(III) (MC4) were prepared and structurally characterized using various spectroscopic and analytical techniques including the validation of molecular structures of ligand (L) and Ni(II)-Tpy complex (MC1). The EPR data demonstrate that MC1 is diamagnetic and other complexes (MC2-MC4) exhibit paramagnetic behavior. Additionally, the structures of ligands and metal complexes were determined using DFT studies and the same were utilized for the docking studies. Interestingly, MC3 and MC4 exhibit a predominant lowest binding energy of −9.62 Kcal/mol (with DNA) and −10.05 Kcal/mol (with BSA) respectively. The binding affinity of the ligand and its complexes with protein and DNA was evaluated by spectroscopic techniques. Notably, the cytotoxicity studies of L and MC1-MC4 were performed against the MCF-7 (human breast cancer) cell lines. The complex MC4 displayed great activity with an IC 50 of 3.5 ± 1.75 μM among all synthesized compounds and comparable with cisplatin. [ABSTRACT FROM AUTHOR]

Introduction: Antioxidants are substances that can counteract or prevent oxidation reactions. Herbal tea is basically a mixture of herbs made from the leaves, seeds, or roots of various plants. one of the innovative ingredients is a combination of Meniran (Phyllanthus niruri Linn.) and red ginger (Zingiber officinale rosc.var Rubrum) plants that contain various active components. Among them, flavonoids that act as antioxidants. The purpose of this study was to determine the antioxidant activity of the combination of meniran and red ginger tea. Methods: Combination tea was made by mixing meniran and red ginger with formulas of 25%, 50% and 75% antioxidants. Data was analyzed by ANOVA statistical test. Antioxidant analysis was conducted using spectrophotometric method. Result: The antioxidant test results showed that the highest antioxidant activity was found in treatment F3 which was 2,585 ppm with consecutive F2 7,485 ppm and F1 9,993 ppm and ascorbic acid as a comparison showed IC50 value of 5,158 mg/L. Conclusion: The meniran (Phyllanthus niruri Linn.) and red ginger (Zingiber officinale rosc.var Rubrum) tea combination showed potential antioxidant activity. [ABSTRACT FROM AUTHOR]

Asiatic acid, a triterpenoid compound, has been shown to have anti-inflammatory activity through the inhibition of the formation of cyclooxygenase-2 (COX-2) in vitro and in vivo. This study was conducted to determine the binding stability and the inhibitory potential of asiatic acid as an anti-inflammatory candidate. The study involved in vitro testing utilizing a colorimetric kit as well as in silico testing for the pharmacophore modeling and molecular dynamic (MD) simulation of asiatic acid against COX-2 (PDB ID: 3NT1). The MD simulations showed a stable binding of asiatic acid to COX-2 and an RMSD range of 1–1.5 Å with fluctuations at the residues of Phe41, Leu42, Ile45, Arg44, Asp367, Val550, Glu366, His246, and Gly227. The total binding energy of the asiatic acid–COX-2 complex is −7.371 kcal/mol. The anti-inflammatory activity of the asiatic acid inhibition of COX-2 was detected at IC50 values of 120.17 µM. Based on pharmacophore modeling, we discovered that carboxylate and hydroxyl are the two main functional groups that act as hydrogen bond donors and acceptors interacting with the COX-2 enzyme. From the results, it is evident that asiatic acid is a potential anti-inflammatory candidate with high inhibitory activity in relation to the COX-2 enzyme.

Tyrosinase is the enzyme involved in melanization and is also responsible for the browning of fruits and vegetables. Control of its activity can be carried out using inhibitors, which is interesting in terms of quantitatively understanding the action of these regulators. In the study of the inhibition of the diphenolase activity of tyrosinase, it is intriguing to know the strength and type of inhibition. The strength is indicated by the value of the inhibition constant(s), and the type can be, in a first approximation: competitive, non-competitive, uncompetitive and mixed. In this work, it is proposed to calculate the degree of inhibition ( i D ), varying the concentration of inhibitor to a fixed concentration of substrate, L-dopa (D). The non-linear regression adjustment of i D with respect to the initial inhibitor concentration [ I ] 0 allows for the calculation of the inhibitor concentration necessary to inhibit the activity by 50%, at a given substrate concentration (IC50), thus avoiding making interpolations between different values of i D . The analytical expression of the IC50, for the different types of inhibition, are related to the apparent inhibition constant ( K I app) . Therefore, this parameter can be used: (a) To classify a series of inhibitors of an enzyme by their power. Determining these values at a fixed substrate concentration, the lower IC50, the more potent the inhibitor. (b) Checking an inhibitor for which the type and the inhibition constant have been determined (using the usual methods), must confirm the IC50 value according to the corresponding analytical expression. (c) The type and strength of an inhibitor can be analysed from the study of the variation in i D and IC50 with substrate concentration. The dependence of IC50 on the substrate concentration allows us to distinguish between non-competitive inhibition ( i D does not depend on [ D ] 0 ) and the rest. In the case of competitive inhibition, this dependence of i D on [ D ] 0 leads to an ambiguity between competitive inhibition and type 1 mixed inhibition. This is solved by adjusting the data to the possible equations; in the case of a competitive inhibitor, the calculation of K I 1 app is carried out from the IC50 expression. The same occurs with uncompetitive inhibition and type 2 mixed inhibition. The representation of i D vs. n, with n = [ D ] 0 / K m D , allows us to distinguish between them. A hyperbolic i D vs. n representation that passes through the origin of coordinates is a characteristic of uncompetitive inhibition; the calculation of K I 2 app is immediate from the IC50 value. In the case of mixed inhibitors, the values of the apparent inhibition constant of meta-tyrosinase (Em) and oxy-tyrosinase (Eox), K I 1 app and the apparent inhibition constant of metatyrosinase/Dopa complexes (EmD) and oxytyrosinase/Dopa (EoxD), K I 2 app are obtained from the dependence of i D vs. n, and the results obtained must comply with the IC50 value. [ABSTRACT FROM AUTHOR]

Identifying new lead molecules to treat cancer requires more than a decade of dedicated effort. Before selected drug candidates are used in the clinic, their anti-cancer activity is generally validated by in vitro cellular experiments. Therefore, accurate prediction of cancer drug response is a critical and challenging task for anti-cancer drugs design and precision medicine. With the development of pharmacogenomics, the combination of efficient drug feature extraction methods and omics data has made it possible to use computational models to assist in drug response prediction. In this study, we propose DeepTTA, a novel end-to-end deep learning model that utilizes transformer for drug representation learning and a multilayer neural network for transcriptomic data prediction of the anti-cancer drug responses. Specifically, DeepTTA uses transcriptomic gene expression data and chemical substructures of drugs for drug response prediction. Compared to existing methods, DeepTTA achieved higher performance in terms of root mean square error, Pearson correlation coefficient and Spearman's rank correlation coefficient on multiple test sets. Moreover, we discovered that anti-cancer drugs bortezomib and dactinomycin provide a potential therapeutic option with multiple clinical indications. With its excellent performance, DeepTTA is expected to be an effective method in cancer drug design. [ABSTRACT FROM AUTHOR]

Aim. Study of antioxidant (antiradical) activity of 6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazine derivatives. Methods. In vitro study of antiradical/scavenging activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals inhibition assay; IC50 values determination. Results. The series of 29 modified derivatives of 6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazine were evaluated for their ability to scavenge DPPH radicals in conditions close to physiological at 5 mM concentration, and the IC50 values were determined for the most promising compounds using the serial dilutions method. The structure - antiradical activity correlations were performed and possible mechanisms of action were discussed. Conclusions. Tested 6,7-dihydro-5Himidazo[ 2,1-b][1,3]thiazine derivatives possess a moderate level of antiradical/scavenging activity. [ABSTRACT FROM AUTHOR]

Fluconazole is the drug of choice for cryptococcal meningitis (CM) monoprophylaxis in resource-limited settings such as Uganda. Emerging fluconazole resistance linked to mutations in the Cryptococcus neoformansERG11 gene (CYP51) has been observed in clinical isolates. Currently, the single nucleotide polymorphisms [SNPs] in the Cryptococcus spp. ERG11 gene that could be responsible for fluconazole resistance are poorly characterized within Ugandan C. neoformans clinical isolates. If available, this information would be useful in the management of cryptococcosis among HIV patients. This cross-sectional study investigates the SNPs present in the coding region of the C. neoformansERG11 gene to determine the relationship between the SNPs identified and fluconazole susceptibility of the clinical isolates. 310 C. neoformans isolates recovered from the Cerebrospinal Fluid (CSF) of patients with HIV and cryptococcal meningitis were examined. The fluconazole half-maximal inhibitory concentrations (IC50 range: 0.25–32 μg/mL) was determined using the microbroth dilution method. A total of 56.1% of the isolates had low IC50 values of <8 μg/mL while 43.9% had high IC50 values ≥ 8 μg/mL. We amplified and sequenced 600 bp of the ERG11 coding sequence from 40 of the clinical isolates. Novel synonymous and 2 missense mutations, S460T and A457V, were identified in the ERG11 gene. The identified SNPs were not associated with differences in fluconazole IC50 values in vitro (p = 0.179). [ABSTRACT FROM AUTHOR]

In this study, water and methanol extracts were obtained from sea buckthorn seeds, which have an important place in health. It was aimed to determine the DPPH, ABTS antioxidant activities and urease, collagenase enzyme inhibition activities of these extracts. The inhibitory effect of the prepared extracts on these enzymes was evaluated by in vitro method. The best DPPH and ABTS scavenging activity was observed in aqueous extracts. DPPH (IC50 = 19.34±0.49 µg/mL) and ABTS (IC50 = 7.24±0.14 µg/mL) were determined. According to DPPH results, while aqueous extract provided 25,85 % removal, the methanolic extract provided 20,44 % removal. In ABTS removal activity, while aqueous extract provided 25,55 % removal, the methanolic extract provided 18,23% removal. The lower the IC50 value, the higher the free radical scavenging power. The best urease and collagenase inhibition from sea buckthorn seed extracts was seen in the aqueous extract (IC50 = 0,23 ± 0,003µg/mL, IC50 = 2,19 ± 1,12µg/mL). Methanol extracts did not show tyrosinase and urease enzyme inhibition. This study clearly shows that sea buckthorn the aqueous extract of can be used as an alternative source of anti-urease and anti-collagenase source. Due to the important role of these enzymes in various diseases, new drugs with inducing or inhibitory effects should be developed. [ABSTRACT FROM AUTHOR]

Titanium dioxide nanoparticles (TiO2NPs) have been extensively used in industry, raising many concerns about their release into the aquatic environments. In marine ecosystems, microalgae are major primary producers; among them, Chaetoceros muelleri is an important microalga in the aquaculture industry as live feed. The impacts of TiO2NPs on the growth, photosynthetic pigments, protein and lipid contents, and the interaction of TiO2NPs with the cell wall of C. muelleri were investigated in the present study. Algal cells were exposed to concentrations of 5, 10, 50, 100, 200, and 400 mg/L TiO2NPs for 10 days. There was a significant difference in the growth between the control and TiO2NPs treatments on each day. The half-maximal inhibitory concentration (IC50) of TiO2NPs on algal cells was found to be 10.08 and 5.01 mg/L on the 3rd and 10th days, respectively. The contents of chlorophyll a and c reduced significantly in the TiO2NPs-treated microalgae. TiO2NPs also reduced the protein and lipid contents in the treated microalgae, up to 13.02% and 47.6% respectively, at the highest concentration. The interaction of TiO2NPs with the C. muelleri cells was obvious based on Fourier transform infrared spectroscopy, microscopic images, EDS, and Mapping analyses. Toxic effects of the released TiO2NPs can damage the stocks of C. muelleri as an important live feed in mariculture. [ABSTRACT FROM AUTHOR]

A series of chloroquine analogs were designed to search for a less toxic chloroquine derivative as a potential SARS‐CoV‐2 Mpro inhibitor. Herein, an ANN‐based QSAR model was built to predict the IC50 values of each analog using the experimental values of other 4‐aminoquinolines as the training set. Subsequently, molecular docking was used to evaluate each analog's binding affinity to Mpro. The analog that showed the greatest affinity and lowest IC50 values was synthesized and characterized for its posterior incorporation into a polycaprolactone‐based nanoparticulate system. After characterizing the loaded nanoparticles, an in vitro drug release assay was carried out, and the cytotoxicity of the analog and loaded nanoparticles was evaluated using murine fibroblast (L929) and human lung adenocarcinoma (A549) cell lines. Results show that the synthesized analog is much less toxic than chloroquine and that the nanoparticulate system allowed for the prolonged release of the analog without evidence of adverse effects on the cell lines used; therefore, suggesting that the analog could be a potential therapeutic option for COVID‐19. [ABSTRACT FROM AUTHOR]

TNBG-5602, a novel anticancer drug candidate, may induce the expression of PPARγ, causing targeted lipotoxicity in cancer tissues. In this study, the in vivo metabolism in rats, in vitro metabolism in recombinant cytochromes, molecular docking for the CYP binding site, and pharmacokinetics in rats were explored to better understand TNBG-5602′s in vivo fate and behavior. Thirteen metabolites were identified using a high-resolution mass spectrometry method, and metabolizing pathways of TNBG-5602 were proposed. Results suggest that TNBG-5602 could be metabolized by CYP450s, while CYP2D6 may play an important role in its in vivo metabolism. The main metabolizing sites of TNBG-5602 are the amino group on the side chain and rings A and E in the molecule. TNBG-5602 is a potent CYP2D6 inhibitor, with an IC50 value of 2.52 μM. An interaction responsible for its metabolism is formed by the NH on the side chain bonding with the ASP301 on the CYP2D6. The pharmacokinetics in rats after a single intravenous administration were fitted to a two-compartment model. The clearance was 0.022 L min−1, and the elimination half-life was 710.9 min. The distribution volume of the peripheral compartment was 1.88-fold that of the central compartment, while the K12 was 1.5-fold that of K21. In conclusion, these studies have not only revealed the metabolizing pathways of TNBG-5602 using in vivo and in vitro methodology, but they have also provided the pharmacokinetic characteristics of TNBG-5602 in rats. The results suggest that TNBG-5602 has good drug developability in terms of pharmacokinetic behaviors. [ABSTRACT FROM AUTHOR]

Objectives: Platinum-based chemotherapies are currently the first-line treatment of non-small cell lung cancer. This study will improve our understanding of the causes of resistance to cisplatin, especially in lung adenocarcinoma (LUAD) and provide a reference for therapeutic decisions in clinical practice.Methods: Cancer Cell Line Encyclopedia (CCLE), The Cancer Genome Atlas (TCGA) and Zhongshan hospital affiliated to Fudan University (zs-cohort) were used to identify the multi-omics differences related to platinum chemotherapy. Cisplatin-resistant mRNA and miRNA models were constructed by Logistic regression, classification and regression tree and C4.5 decision tree classification algorithm with previous feature selection performed via least absolute shrinkage and selection operator (LASSO). qRT-PCR and western-blotting of A549 and H358 cells, as well as single-cell Seq data of tumor samples were applied to verify the tendency of certain genes.Results: 661 cell lines were divided into three groups according to the IC50 value of cisplatin, and the top 1/3 (220) with a small IC50 value were defined as the sensitive group while the last 1/3 (220) were enrolled in the insensitive group. TP53 was the most common mutation in the insensitive group, in contrast to TTN in the sensitive group. 1348 mRNA, 80 miRNA, and 15 metabolites were differentially expressed between 2 groups (P < 0.05). According to the LASSO penalized logistic modeling, 6 of the 1348 mRNAs, FOXA2, BATF3, SIX1, HOXA1, ZBTB38, IRF5, were selected as the associated features with cisplatin resistance and for the contribution of predictive mRNA model (all of adjusted P-values < 0.001). Three of 6 (BATF3, IRF5, ZBTB38) genes were finally verified in cell level and patients in zs-cohort.Conclusions: Somatic mutations, mRNA expressions, miRNA expressions, metabolites and methylation were related to the resistance of cisplatin. The models we created could help in the prediction of the reaction and prognosis of patients given platinum-based chemotherapies. [ABSTRACT FROM AUTHOR]

In this study, Poly (N-tert- amylacrylamide-co-Acrylamide/AMPSNa) hydrogels (HG37, HG38, HG39, and HG40) were prepared by free-radical copolymerization of N-tert-amyl acrylamide (NTA), acrylamide (AM), and 2-Acrylamido-2-methyl-1-propane sodium sulfonate (AMPSNa). The hydrogels were characterized using FTIR, XRD, SEM, and TGA. The adsorption of bovine serum albumin (BSA) was evaluated at various pH levels and with different amounts of AMPSNa. Protein adsorption was shown to vary depending on pH and the amount of ionic monomer present. The BSA adsorption was complemented with XRD, SEM, and TGA. The maximum protein adsorption was reported at a pH of 5.0 which is closer to that of IEP. When assessed in vitro, the hydrogels were found to be effective in reducing biofilm formation (MTP assay) by Staphylococcus aureus (IC50 -20.45 µg/mL) and Pseudomonas aeruginosa (IC50 - 46.64 µg/mL). These hydrogels inhibited the formation of zoospores of the marine alga Ulva Lactuca (47.41 percent), indicating antimarine fouling activity in vitro. [ABSTRACT FROM AUTHOR]

Due to their small sizes and high reactivity, nanoparticles have a completely different toxicity profile than larger particles, and it is difficult to predict their potential ecological impact. There is a need for broad ecotoxicological studies of nanomaterials in order to specify their environmental impact and ensure safe application of nanotechnology products. In this work, we have assessed the toxicity of Au and Au/ZnO metal nanoparticles obtained with the use of Tanacetum parthenium (herba) extract. The obtained nanoparticles were characterized by UV–Vis spectrophotometry (UV–VIS), Transmission electron microscopy (TEM), Atomic force microscopy (AFM), and Fourier transform infrared spectroscopy (FTIR). In order to assess the toxicity of biologically synthesized nanoparticles, we used seeds of various plants: Lepidium sativum, Linum flavum, Zea mays, Salvia hispanica-chia, Lupinus angustifolius, Petroselinum crispum subsp. Crispum, Beta vulgaris, Phaseolus vulgaris. The in vitro phytotests showed that gold nanoparticles at a specific range of concentrations for all plants stimulated their growth. The highest growth activity was exhibited by the solution at the concentration of 0.300 mg/ml towards corn (Aw ≈ − 135 ± 16) and flax (Aw ≈ − 44 ± 10). Only for parsley the IC50 was determined at 0.57 mg/ml, but solutions at the concentration of 0.030 to 0.150 mg/ml also stimulated plant growth. Au/ZnO had a toxic effect at all concentrations applied in the study. [ABSTRACT FROM AUTHOR]

Background and Objectives: Cancer is believed to be one of the main challenges to health care profession and compounds isolated from natural products play significant role in treatment of cancer. Sarcococca saligna (Buxaceae) contains variety of steroidal alkaloids having numerous pharmacological and biological potentials. Hence, current research work was designed to isolate steroidal alkaloids from Sarcococca saligna and to evaluate it for antioxidant and cytotoxic activity. Materials and Methods: Compounds Alkaloid-C, Dictyophlebine, Sarcovagine-D and Holaphylline were purified by column chromatography followed by spectroscopic techniques for their structure confirmation. Antioxidant and cytotoxic activities were investigated against DPPH and HeLa cell lines using ascorbic acid and doxorubicin as standard. Results: The radical scavenging effect produced by Holaphylline and Sarcovagine-D was 80.0±3.20 and 78.0±3.20 % at 400 µg/ml concentration which was statistically similar to that of standard, while on the same concentration inhibition for Dictyophlebine and Alkaloid-C was 10.0±0.00% and 20±1.01 %. In addition, Holaphylline showed less anticancer activity (23.88±0.243) in cell growth of HeLa cell followed by Alkaloid-C (12.9±0.235), Dictyophlebine (6.1±0.345), while S cytotoxic effect for Sarcovagine-D was high (5.1±0.14) in (IC50), which exhibiting statistical variation from Doxorubicin (2.1±0.14%). Conclusion: This study provided scientific report and importance of the use of steroidal alkaloids from Sarcococca saligna as an antioxidant and cytotoxic against agents' HeLa cell lines that may provide a new scope toward the development of novel drugs for cancer remedy. [ABSTRACT FROM AUTHOR]

Toxoplasmosis is a highly prevalent human disease, and virulent strains of this parasite emerge from wild biotopes. Here, we report on the potential of a histone deacetylase (HDAC) inhibitor we previously synthesized, named JF363, to act in vitro against a large panel of Toxoplasma strains, as well as against the liver and blood stages of Plasmodium parasites, the causative agents of malaria. In vivo administration of the drug significantly increases the survival of mice during the acute phase of infection by T. gondii, thus delaying its spreading. We further provide evidence of the compound's efficiency in controlling the formation of cysts in the brain of T. gondii-infected mice. A convincing docking of the JF363 compound in the active site of the five annotated ME49 T. gondii HDACs was performed by extensive sequence–structure comparison modeling. The resulting complexes show a similar mode of binding in the five paralogous structures and a quite similar prediction of affinities in the micromolar range. Altogether, these results pave the way for further development of this compound to treat acute and chronic toxoplasmosis. It also shows promise for the future development of anti-Plasmodium therapeutic interventions. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor tyrosine kinase domain (EGFR‐TK) has been one of the prominent targets for therapeutics of several human cancers, in particular non‐small cell lung cancer. Although several small chemical compounds targeting EGFR‐TK have been approved by FDA for treatment of such a cancer, the discovery of a new class of EGFR‐TK inhibitors, for example, small peptides, is still desired. In this study, using molecular docking‐based virtual screening, we selected five small peptides with high docking scores from eight thousand peptides as candidate compounds against EGFR‐TK. Among five, the tripeptide WFF had the most potency to suppress the survival of non‐small cell lung cancer cells but had the least toxicity to human liver cancer cells. Our in vitro kinase assays showed that WFF exhibited much lower inhibitory activity against purified EGFR‐TK than the drug erlotinib (i.e., IC50 values of ≈ 0.62 μM vs ≈ 7.57 nM, respectively). The relative free binding energies estimated from molecular dynamic simulations were consistent with the in vitro experiments in which the WFF bound had a lower affinity than erlotinib bound to EGFR‐TK (i.e., ΔGbind values of −20.3 kJ/mol vs ≈ −126.8 kJ/mol, respectively). In addition, the simulation analyses demonstrated the difference in EGFR binding preference between the drug and tripeptide in which erlotinib was stably bound in the ATP‐binding pocket for 4‐anilinoquinazoline class of inhibitors, while WFF moved out of that pocket to interact with polar amino acid residues on the αC‐helix, activation loop, and substrate‐binding region. Our findings suggest preferable interactions of the potential tripeptide on enzyme inhibition that are useful for further development of a new class of inhibitors targeting EGFR‐TK. [ABSTRACT FROM AUTHOR]