Percentage Of Growth Inhibition Research Articles

Antifungal Activity of ZnO Nanobullets against Schizosaccharomyces pombe

In this study, an enhanced antifungal response of ZnO nanobullets (NBs) against Schizosaccharomyces pombe is reported. The ZnO NBs were prepared by alkali precipitation method and confirmed by microscopic, morphological and optical studies using SEM, EDX, TEM, HRTEM and photoluminescence (PL) spectroscopic techniques. Growth kinetics and MIC studies were conducted following the growth inhibition percentage studies. Colony forming assay, well diffusion, disc diffusion, N-acetyl cysteine (NAC) effect on S. pombe growth, trypan blue study, cellular reactive oxygen species (ROS) quantification using H2DCFDA dye, Bradford assay, DNA fragmentation and all other relevant protocols were performed in antifungal studies. ZnO nanobullets (NBs) were shown by SEM and TEM examinations to have an average size of 50 nm. The hexagonal wurtzite structure of ZnO NBs was confirmed by HRTEM’s lattice fringe findings. Defectrelated visible emissions at 412, 436, 457 and 564 nm were confirmed via PL analysis. It was found that ZnO NBs resulted in complete growth inhibition of S. pombe at 200 μg/mL. When S. pombe was treated with ZnO NBs, the Bradford assay revealed enhanced protein leakage, but the TBARS assay revealed lipid peroxidation brought on by reactive oxygen species (ROS). When S. pombe was exposed to ZnO NBs, the H2DCFDA assay revealed increased ROS generation, whilst the trypan blue assay revealed increased cell membrane fusion and lower viability. According to present study, the treatment with ZnO NBs caused S. pombe to develop damaged cell walls, leaky proteins and DNA breakage.

In-vitro Compatibility Assessment of Trichoderma harzianum with Chemical Fungicides and Botanical Extracts

The threats of devastating soil-borne disease, limited availability of its management strategies, development of fungicide-resistant strains, outbreaks of new diseases, and growing concerns regarding nature and the environment have compelled us to use integrated disease management (IDM) strategies with appropriate biocontrol agents. Trichoderma, free-living fungi, are successful antagonists with promising biocontrol potentials and can be used with chemicals and botanicals in the IDM approach to control various plant pathogenic fungi. So, the present experiment was conducted to evaluate the compatibility of Trichoderma harzianum with chemical fungicides and botanicals in in-vitro using a poisoned food technique. The experiment was conducted in a completely randomized design with three replications for each treatment at the central laboratory of the Institute of Agriculture and Animal Science, Lamjung, Nepal, and data were taken at different time intervals and analyzed. For fungicides, the maximum compatibility was found in Copper oxychloride at 100 ppm, and the highest inhibition (100%) was observed in Carbendazim + Mancozeb, Carbendazim, and Hexaconazole even in lower concentration (100 ppm). For botanicals, Azadirachta indica and Zingiber officinale enhanced T. harzianum, and the highest compatibility was observed at 10% leaves extract of Azadirachta indica with a growth inhibition percentage of -5.43% (Day 5). Aqueous extracts of tested botanicals were found compatible with T. harzianum, except for the Acorus calamus, Artemisia vulgaris, and Allium sativum. In IDM practice, compatible fungicides and botanicals at recommended doses can be used with T. harzianum.

Fabrication of PLGA Nanoparticles Using Combination of PCL-PVA-PEG Copolymer as Surfactant: In-Vitro Characterization and Cytotoxicity Study

Objective: The present study aimed to fabricate Poly lactic acid co-glycolic acid (PLGA) nanoparticles loaded with resveratrol using a novel graft co-polymer surfactant named Soluplus®. Methods: The PLGA nanoparticles were prepared in the present study using polyvinyl caprolactam polyvinyl acetate polyethylene glycol amphiphilic graft copolymer named Soluplus® as surfactant through double emulsification and single emulsification-solvent evaporation method. The formulations were prepared successfully to encapsulate the drug resveratrol, and then evaluated for their particle size, polydispersity index, zeta potential, drug loading and the degree of entrapment of the drug. A scanning electron microscope was used to examine the morphology of the nanoparticles. In vitro drug release was assessed and, mathematical pharmacokinetic modelling was done to assess the release pattern. A comparative cytotoxicity study between free drug and prepared nanoparticles using MTT assay was carried out for cell viability evaluation. Uptake and internalization of nanoparticles were also studied using confocal fluorescence microscopy. Results: The results demonstrated successful fabrication of the PLGA nanoparticles using the Soluplus as polymer surfactant. The drug, polymer and the all the excipients were found to be compatible and did not indicate any interaction. The results also indicated the prepared nanoparticles (SF2) as suitable resveratrol delivery vehicle in terms of the compliant particle size (344.6 ±6.63 nm), polydispersity index (0.962), zeta potential (- 18.5±1.21), drug loading (18.94± 0.27%), the entrapment efficiency (39.62±0.17%) and drug release (75.13±0.17%). The shape and surface morphology of the formulated nanoparticles were found to be spherical and smooth. Cytotoxicity study also demonstrated significant reduction of cell viability by the nanoparticle compared to free resveratrol. The highest cytotoxicity of SF2 against MCF7 cell was found in 2000 nM concentration with 3.03±0.05 percent of cell viability. It was found that the percentage of growth inhibition was increasing with increasing concentration of SF2 and IC50 value of this assay was 108.94 μg/ml. Conclusion: It has been found that the Resveratrol loaded PLGA nanoparticles were successfully formulated and found to perform better in terms of efficacy and cytotoxicity.

In vitro evaluation of antagonistic potentiality of Trichoderma harzianum against Diplodia spp. phytopathogenics fungi

BackgroundTrichoderma species are able to cause significant changes in the metabolism of host plants, by that means it trigger the plant growth and increasing plant defense to diverse fungal diseases. Trichoderma harzianum has been identified as potential biocontrol agent of many phytopathogenic fungi. Therefore, the aim of this study was to assess in vitro antagonistic activity against three Diplodia isolates utilizing direct and remote confrontations methods.ResultsThe results revealed that T. harzianum inhibited mycelial growth of the three phytopathogenic fungi compared to the untreated control. The percentage of growth inhibition of T. harzianum against Diplodia isolates ranged between 58 and 79% for direct confrontation and between 31 and 46% remote confrontation. Considerable antagonistic abilities of T. harzianum were exhibited against all tested Diplodia isolates. The results of both confrontations showed that the radial growth of the fungal pathogens was statistically significant (P < 0.001) and influenced by the antagonist on 6 days following incubation.ConclusionThe findings may reveal a valuable knowledge that may be further used to find a suitable biological control contrariwise Botryosphaeria dieback caused by Diplodia species.

Costs and Causes of Oncology Drug Attrition With the Example of Insulin-Like Growth Factor-1 Receptor Inhibitors

The development of oncology drugs is expensive and beset by a high attrition rate. Analysis of the costs and causes of translational failure may help to reduce attrition and permit the more appropriate use of resources to reduce mortality from cancer. To analyze the causes of failure and expenses incurred in clinical trials of novel oncology drugs, with the example of insulin-like growth factor-1 receptor (IGF-1R) inhibitors, none of which was approved for use in oncology practice. In this cross-sectional study, inhibitors of the IGF-1R and their clinical trials for use in oncology practice between January 1, 2000, and July 31, 2021, were identified by searching PubMed and ClinicalTrials.gov. A proprietary commercial database was interrogated to provide expenses incurred in these trials. If data were not available, estimates were made of expenses using mean values from the proprietary database. A search revealed studies of the effects of IGF-1R inhibitors in preclinical in vivo assays, permitting calculation of the percentage of tumor growth inhibition. Archival data on the clinical trials of IGF-1R inhibitors and proprietary estimates of their expenses were examined, together with an analysis of preclinical data on IGF-1R inhibitors obtained from the published literature. Expenses associated with research and development of IGF-1R inhibitors. Sixteen inhibitors of IGF-1R studied in 183 clinical trials were found. None of the trials, in a wide range of tumor types, showed efficacy permitting drug approval. More than 12 000 patients entered trials of IGF-1R inhibitors in oncology indications in 2003 to 2021. These trials incurred aggregate research and development expenses estimated at between $1.6 billion and $2.3 billion. Analysis of the results of preclinical in vivo assays of IGF-1R inhibitors that supported subsequent clinical investigations showed mixed activity and protocols that poorly reflected the treatment of advanced metastatic tumors in humans. Failed drug development in oncology incurs substantial expense. At an industry level, an estimated $50 billion to $60 billion is spent annually on failed oncology trials. Improved target validation and more appropriate preclinical models are required to reduce attrition, with more attention to decision-making before launching clinical trials. A more appropriate use of resources may better reduce cancer mortality.

The Oncolytic Effect of an Iraqi Newcastle Disease Virus Attenuated Strain (AMHA1) Against Colorectal Cancer Cells.

Objective: The most recent World Health Organization statistics show that colorectal cancer is the third foremost cause of death by cancer among Iraqis. It has become necessary to search and develop novel and unconventional treatment methods. Oncolytic virotherapy is one of the innovative cancer therapeutics that showed to be safe and selective and there is increased efforts in the recent years to move them to clinic. For the reason we were developing our Iraqi strain of oncolytic NDV to fight colorectal cancer. Materials and Methods: This study tested the killing rate of Iraqi strain of Newcastle disease virus (AMHA1) on colorectal cancer cells and testing the safety on normal cells. The virus tittered using vero cells, and then the cytotoxic effect of the virus on both types of cells was determined using the crystal violet assay. Finally, we performed a morphological analysis using hematoxylin and eosin staining. Results: Newcastle disease virus 0.3 MOI causes significant cytotoxicity with prominent cytopathic effect in the colorectal cancer cell line HRT-18G with 50% percentage of growth inhibition, but not in the normal human fibroblast (NHF) percentage of growth inhibition where it was less than 20%. Conclusion oncolytic NDV AMHA1 strain effective against colorectal cancer cells because it has selectivity in replication and safety profile.

Halogen substituted aurones as potential apoptotic agents: synthesis, anticancer evaluation, molecular docking, ADMET and DFT study

A series of halogen-substituted aurone derivatives (2a-k) were synthesized and evaluated for an anti-proliferative study against NCI 60 cancer cell line panel and showed that most of the compounds predominantly exhibited promising activity against MCF-7. Compound 2e exhibited promising anticancer activity against the MCF-7 cancer cell line with 84.98% percentage growth inhibition in a single dose assay of 10 μM with an IC50 value of 8.157 ± 0.713 μM. In apoptotic assay, the effect of compound 2e on the cell cycle progression indicated that exposure of MCF-7 cells to compound 2e induced a significant disruption in the cell cycle profile including a time-dependent decrease in the cell population at G0/G1 and G2/M phase and arrests the cell cycle at the S phase. In silico, molecular docking ADME and toxicity studies of all compounds were also carried out. The docking study revealed that all the aurone derivatives displayed good docking scores ranging from −7.066 to −8.573. The results of Molecular Electrostatic Potential Mapping (MESP) and Density Functional Theory (DFT) studies of the most active compound 2e and least active compound 2k also favoured the experimental results.

Design, Synthesis, ADME, and Anticancer Studies of Newer N-Aryl-5-(3,4,5-Trifluorophenyl)-1,3,4-Oxadiazol-2-Amines: An Insight into Experimental and Theoretical Investigations.

In continuance of our investigation into the anticancer activity of oxadiazoles, we report here the preparation of 10 new 1,3,4-oxadiazole analogues using the scaffold hopping technique. We have prepared the oxadiazoles having a common pharmacophoric structure (oxadiazole linked aryl nucleus) as seen in the reported anticancer agents IMC-038525 (tubulin inhibitor), IMC-094332 (tubulin inhibitor), and FATB (isosteric replacement of the S of thiadiazole with the O of oxadiazole). All of the oxadiazole analogues were predicted for their absorption, distribution, metabolism, and excretion (ADME) profiles and toxicity studies. All of the compounds were found to follow Lipinski's rule of 5 with a safe toxicity profile (Class IV compound) against immunotoxicity, mutagenicity, and toxicity. All of the compounds were synthesized and characterized using spectral data, followed by their anticancer activity tested in a single-dose assay at 10 μM as reported by the National Cancer Institute (NCI US) Protocol against nearly 59 cancer cell lines obtained from nine panels, including non-small-cell lung, ovarian, breast, central nervous system (CNS), colon, leukemia, prostate, and cancer melanoma. N-(2,4-Dimethylphenyl)-5-(3,4,5-trifluorophenyl)-1,3,4-oxadiazol-2-amine (6h) displayed significant anticancer activity against SNB-19, OVCAR-8, and NCI-H40 with percent growth inhibitions (PGIs) of 86.61, 85.26, and 75.99 and moderate anticancer activity against HOP-92, SNB-75, ACHN, NCI/ADR-RES, 786-O, A549/ATCC, HCT-116, MDA-MB-231, and SF-295 with PGIs of 67.55, 65.46, 59.09, 59.02, 57.88, 56.88, 56.53, 56.4, and 51.88, respectively. The compound 6h also registered better anticancer activity than Imatinib against CNS, ovarian, renal, breast, prostate, and melanoma cancers with average PGIs of 56.18, 40.41, 36.36, 27.61, 22.61, and 10.33, respectively. Molecular docking against tubulin, one of the appealing cancer targets, demonstrated an efficient binding within the binding site of combretastatin A4. The ligand 6h (docking score = -8.144 kcal/mol) interacted π-cationically with the residue Lys352 (with the oxadiazole ring). Furthermore, molecular dynamic (MD) simulation studies in complex with the tubulin-combretastatin A4 protein and ligand 6h were performed to examine the dynamic stability and conformational behavior.

Antifungal activity of myco-synthesized bimetallic ZnO-CuO nanoparticles against fungal plant pathogen Fusarium oxysporum

Fusarium species are considered one of the most destructing plant pathogens. In the current study, bimetallic zinc oxide-copper oxide nanoparticles (ZnO-CuO NPs) were myco-synthesized using Aspergillus fumigatus for controlling Fusarium oxysporum growth. Aspergillus fumigatus was isolated from soil and identified morphologically and genetically. The myco-synthesized ZnO-CuO NPs were characterized using UV-Vis, DLS, HR-TEM, SEM, and XRD analyses. HR-TEM characterization method indicated that, the biosynthesized bimetallic ZnO-CuO NPs appeared as semi-spherical with the average diameter specified as 54.18 ± 1.9 nm. The DLS method described the characteristic particle size diffusion and was calculated as 85.52 nm, 90.85 nm, and 92.85 nm for ZnO NPs, CuO NPs, and ZnO-CuO NPs, respectively. Additionally, the SEM image of ZnO-CuO NPs displays basic NP surface character and the exterior impression was apparent. The biosynthesized ZnO-CuO NPs were separated naturally as spherical particles connected within the fungal filtrate, which displays as illuminated NPs fused and capped with the fungal filtrate. Antifungal activity of bimetallic ZnO-CuO NPs was evaluated against F. oxysporum. Results revealed that bimetallic ZnO-CuO NPs exhibited promising antifungal activity toward F. oxysporum where inhibition zone at 1000 µg/ml was 22.8 ± 0.76 mm, and MIC was 125 µg/ml. Moreover, growth inhibition percentages of F. oxysporum at different concentrations of bimetallic ZnO-CuO NPs 1000, 500, 250, and 125 µg/ml were 88.9, 65.5, 41.1, and 8.9% respectively, where the highest inhibition was 88.9% at concentration 1000 µg/ml, while the lowest inhibition was 8.9% at concentration 125 µg/ml. In TEM ultrastructure results, the treated F. oxysporum with ZnO-CuO NPs, a clear destruction was found in all cell contents and disintegration of the cell wall as well as destruction of the plasma membrane. Also, the nucleus appeared as small size and damaged shape and the chromatin materials distributed with several dark stained bodies in cytoplasm. In conclusion, bimetallic ZnO-CuO NPs were successfully myco-synthesized using A. fumigatus, where it had promising antifungal activity against F. oxysporum.

Phytoconstituents and antidermatophytic activity of crude extracts of Senna occidentalis

Dermatophytes are one of the major aetiologic agents of cutaneous mycoses Senna occidentalis is among the plants used in traditional herbal medicine in treating fungal skin infections and it is shown from literature to contain phytochemicals which are attributed to its antidermatophytic activity. This work is aimed at determining the Phytoconstituents and antidermatophytic activity of leaves and seeds crude extracts of the Senna occidentalis plant . The study is a qualitative study that determines the phytoconstituents and antidermatophytic activity of the plant extracts on some clinical dermatophyte isolates. The plant parts were sampled and were used to obtain aqueous and n-hexane extracts using distilled water and n-hexane as extracting solvents respectively. Phytochemical analysis was done on the extracts to determine the presence of secondary metabolites. The antidermatophytic activity of the extracts on clinical dermatophytes isolates was determined using poisoned food technique. Aqueous extraction gave higher percentage extraction yield than n-hexane extract . All extracts contain secondary metabolites and the extracts showed varying degree of percentage growth inhibition on the isolates. Phytochemical screening of the leaves and seeds extracts of Senna occidentalis revealed the presence of alkaloids, saponins, tannins and other phytoconstituents. The Senna occidentalis leaves and seeds extracts showed growth inhibition percentage (I) ranging between 9% to 39.8% for n-hexane leaf extract,1.3% to 52.6% for aqueous leaf extract,2.6% to 57.2% for n-hexane seed extract and 12.8% to 61.1% for aqueous seed extract. Senna occidentalis leaves and seeds extract have shown varying potential in inhibiting dermatophyte growth with no extract having 100% inhibition percentage on all the tested dermatophytes.&#x0D;

Green Synthesised TiO2 Nanoparticles-Mediated Terenna asiatica: Evaluation of Their Role in Reducing Oxidative Stress, Inflammation and Human Breast Cancer Proliferation.

Oxidative stress and chronic inflammation interplay with the pathogenesis of cancer. Breast cancer in women is the burning issue of this century, despite chemotherapy and magnetic therapy. The management of secondary complications triggered by post-chemotherapy poses a great challenge. Thus, identifying target-specific drugs with anticancer potential without secondary complications is a challenging task for the scientific community. It is possible that green technology has been employed in a greater way in order to fabricate nanoparticles by amalgamating plants with medicinal potential with metal oxide nanoparticles that impart high therapeutic properties with the least toxicity. Thus, the present study describes the synthesis of Titanium dioxide nanoparticles (TiO2 NPs) using aqueous Terenna asiatica fruit extract, with its antioxidant, anti-inflammatory and anticancer properties. The characterisation of TiO2 NPs was carried out using a powdered X-ray diffractometer (XRD), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray diffraction (EDX), high-resolution transmission electron microscopy (HR-TEM), dynamic light scattering (DLS), and zeta-potential. TiO2 NPs showed their antioxidant property by scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals in a dose-dependent manner with an IC50 value of 80.21 µg/µL. To ascertain the observed antioxidant potential of TiO2 NPs, red blood cells (RBC) were used as an in vitro model system. Interestingly, TiO2 NPs significantly ameliorated all the stress parameters, such as lipid peroxidation (LPO), protein carbonyl content (PCC), total thiol (TT), superoxide dismutase (SOD), and catalase (CAT) in sodium nitrite (NaNO2)-induced oxidative stress, in RBC. Furthermore, TiO2 NPs inhibited RBC membrane lysis and the denaturation of both egg and bovine serum albumin, significantly in a dose-dependent manner, suggesting its anti-inflammatory property. Interestingly, TiO2 NPs were found to kill the MCF-7 cells as a significant decrease in cell viability of the MCF-7 cell lines was observed. The percentage of growth inhibition of the MCF-7 cells was compared to that of untreated cells at various doses (12.5, 25, 50, 100, and 200 µg/mL). The IC50 value of TiO2 NPs was found to be (120 µg/mL). Furthermore, the Annexin V/PI staining test was carried out to confirm apoptosis. The assay indicated apoptosis in cancer cells after 24 h of exposure to TiO2 NPs (120 µg/mL). The untreated cells showed no significant apoptosis in comparison with the standard drug doxorubicin. In conclusion, TiO2 NPs potentially ameliorate NaNO2-induced oxidative stress in RBC, inflammation and MCF-7 cells proliferation.

Biological Control of Fungal Phytopathogens with Trichoderma harzianum and Its Fungicidal Compatibility

Excessive synthetic fungicide use reduces soil's antagonistic population, allowing soil-borne plant pathogens to cause significant global losses. Despite high fungicide application, plant diseases persist, harming the ecosystem. Trichoderma spp, an eco-friendly plant symbiont, can serve as an alternative biocontrol agent. This study evaluated Trichoderma harzianum's antagonistic effect against fungal pathogens and its compatibility with fungicides under in-vitro using a Completely Randomized Design with four replications per treatment. Trichoderma harzianum showed high antagonistic activity for Alternaria brassicicola (70.35%), Fusarium solani (70.82%), Helminthosporium sorokinana (66.55%), Rhizoctonia solani (78.58%), Sclerotium rolfsii (92.53%). Among the tested fungicides, Copper oxychloride and Mancoxeb at 400 ppm showed maximum compatibility with growth inhibition percent (GIP) of 2.41% and 7.91%, respectively, after 60 hours of incubation. Fungicides viz., Carbendazim, Hexaconazole, and Carbendazim+Mancozeb at all concentrations aren't compatible with 100% GIP throughout the experiment, and for Metalaxyl+Mancozeb, high growth inhibition percent was observed ranging from 42.77% to 78.40% making it incompatible. In integrated disease management, compatible fungicides at recommended doses can be used in combination with T. harzianum.

Bioefficacy of Lecanoric Acid Produced by Parmotrema austrosinense (Zahlbr.) Hale against Tea Fungal Pathogens

Lichens are symbiotic organisms that are composed of fungal partners and photosynthetic algal partners. During the symbiotic process in lichen thallus, the fungus synthesizes certain secondary metabolites in which lecanoric acid is very important in terms of antibiotic properties. Considering the vital importance of lecanoric acid, the present study aimed to produce lecanoric acid from the thallus of Parmotrema austrosinense lichen using Modified Bold’s basal salt medium and evaluate the bio-efficacy against tea fungal pathogens. Lecanoric acid was purified and confirmed by micro-crystallization method and subsequently bioassayed against tea fungal pathogens. The results revealed that lecanoric acid registered a significant antifungal activity in terms of the growth inhibition of test pathogens. Companion systemic and botanical fungicides were found to be inferior to lecanoric acid in the percentage of growth inhibition. The inhibition rate varied among tea pathogens. Of the tea pathogens tested, tea leaf disease-causing pathogens including Cercospora theae (C. theae), Glomerella cingulata (G. cingulate), and Phomopsis theae (P. theae) showed the highest percentage of growth inhibition followed by stem and root rot diseases. The present study suggests that lecanoric acid showed an inhibitory effect against tea pathogens, which might be due to antibiotic properties and fungicidal action of lecanoric acid.

Evaluation of Magonia pubescens A. St.-Hill. Roots Extract against Phytopathogens: Searching for Eco-Friendly Crop Protection Products

Botanical biopesticides have emerged as sustainable and eco-friendly alternatives to synthetic pesticides, whose indiscriminate use leads to several drawbacks to human and environmental health. To the best of our knowledge, there have been no reports on M. pubescens’ bioactivity on phytopathogens affecting crops as a potential fungicide or antifeedant. This has encouraged us to investigate the potential of the roots of this plant as a source of biopesticides. The present study reports on the evaluation of the roots extract from Magonia pubescens A. St.-Hill., a species from the Cerrado (Brazilian savannah), on the phytopathogenic fungi Botrytis cinerea, Fusarium oxysporum, and Alternaria alternata. In addition, its insect antifeedant effect was assayed against Chrysodeixis chalcites. Thus, an in vitro test-assay was used to determine the fungicide potential (percentage growth inhibition, % GI) of the ethanolic extract of this plant species, whereas a leaf-disk bioassay on the 5th instar larvae of C. chalcites was performed to evaluate its insecticidal potential. The ethanolic extract was further fractionated by liquid–liquid partition using solvents of increasing polarity. The hexane/dichloromethane fraction exhibited a moderated potency and was similar to the ethanolic extract on the three assayed fungi (around % GI 30 at 1 mg/mL), whereas the n-butanol fraction showed a slight improvement of the fungicide effect against B. cinerea (% GI 39.18 at 1 mg/mL). Moreover, the ethanolic extract exhibited a strong antifeedant activity, with a refusal rate (FR) higher than 90% in both choice and non-choice assays against C. chalcites, while the ethyl acetate and n-butanol fractions behaved as appetite suppressors. These results highlight M. pubescens as a promising source of biopesticides and deserve further investigations to optimize extraction procedures.

Anti-tumor Efficacy and Safety of the BAG3/HSP70 Inhibitor YM-1 ina Triple Negative Breast Cancer Model

Patients who treat with TNBC are usually with intense chemotherapy. Recently, BAG3 has been suggested as apotential therapeutic target for cancer. However, inhibiting BAG3 for therapy may result in unintended damage tocardiomyocytes. Thus, this research proposal will test whether or not the inhibition of BAG3 will significantly affectthe heart while still having potent anti-tumor efficacy. Human TNBC cell line BT-549 cells will be inoculated into CB17/SCID mice. When the tumor grows to 100 mm3, mice will be intraperitoneally injected with different doses of YM1, an inhibitor of BAG3/HSP70. The clinically used TNBC chemotherapy drug doxorubicin will be used as the positivecontrol. The tumor growth, expressed as the change in tumor volume and tumor growth inhibition percentage (TGI),will be measured. Troponin I level in the serum, ECG measurement, and Hematoxylin and Eosin staining will be used toassess heart damage. The results of our study will indicate whether the animals will tolerate the BAG3 inhibitor, YM-1,at its effective doses and whether inhibition of BAG3 may be a better option, particularly regarding unwanted effects oncardiomyopathy, compared to standard of care in TNBC. Future investigations are warranted.

Silicon Phthalocyanines as Anti‐infectious, Antioxidant, and Anticancer Agents

AbstractThis study reports the synthesis of three silicon phthalocyanines (SiPc1–3) bearing 2‐dimethylaminoethoxy, 2‐[2‐(dimethylamino)ethoxy]ethoxy, or 2‐{2‐[2‐(dimethylamino)ethoxy]ethoxy}ethoxy on axial positions. Also, their quaternized derivatives (SiPcQ1–3) were prepared. The effect of ligand length on the biological features of water‐soluble silicon phthalocyanines (SiPcQ1–3) was investigated. The highest antimicrobial activity was obtained 32 μg/mL for SiPcQ1 against double‐distilled water, E. hirae, and E. faecalis. The growth inhibition percentages of compounds SiPcQ1–3 were obtained 100 %, 100 %, and 85.14 %, respectively. The highest biofilm inhibition activity was obtained 86.16 % for 250 mg/L SiPcQ3 against S. aureus. The E. coli growth inhibition activities of 50 mg/L compounds SiPcQ1–3 ranged from 60.17 % to 87.53 % and their activities increased (73.46 %–95.37 %) by the enhancement of the concentration. The E. coli viability inhibition activities of SiPcQ1–3 were concentration‐dependent. The DNA cleavage and binding properties of SiPcQ1–3 were studied using pBR322 DNA and CT‐DNA, respectively. Besides, the toxicity of SiPcQ1–3 was examined against the human colon cancer cell line (DLD‐1). The IC50 values of compounds (SiPcQ1–3) were obtained between 10.12 and 27.06 μM in the dark, however, these values were calculated between 12.32 and 22.17 μM under the light. SiPcQ3 exhibited the highest in vitro anticancer activity against the tested cell.

Yeast Mixtures for Postharvest Biocontrol of Diverse Fungal Rots on Citrus limon var Eureka

Mexico is among the most important citrus fruit producers in the world. However, during storage, several problems related to fungi can arise. The most common fungal postharvest diseases detected on Citrus limon var Eureka (Italian lime) produced in the Tamaulipas state are green/blue mold (Penicillium spp.), fusarium rot (F. oxysporum, F. solani, F. proliferatum, among others), and anthracnose (Colletotrichum spp.). In this work, we selected yeasts, occurring as the natural epiphytic mycoflora of lemons or from fermented traditional products, to be tested as part of a formulation for protecting stored lemons against fungal diseases. The best-performing yeasts, labeled as LCBG-03 (Meyerozyma guilliermondii), LCBG-30 (Pseudozyma sp.), and LCBG-49 (Saccharomyces cerevisiae), were selected to test their compatibility and biocontrol performance against strains of Penicillium digitatum (AL-38), Fusarium sp. (AL-21), Colletotrichum gloeosporioides (AL-13), and Epicoccum sorghinum (H3A). Based on their in vitro performance regarding the percentage of radial growth inhibition, both applied individually or as two yeasts mixed at equal cellular concentrations, the best combinations (containing M. guilliermondii formulated with either Pseudozyma sp. or S. cerevisiae) were selected with efficacies higher than 95% in both in vitro fungal radial growth rate inhibition and on stored lemon fruits. This work contributes to the search for compatible yeast combinations with the aim to diminish the fungal losses of citrus fruits using biocontrol for citrus postharvest protection.

Plant Extracts Control In Vitro Growth of Disease-Causing Fungi in Chayote.

The use of agrochemicals has caused environmental problems and toxicity to humans, so natural alternatives for disease control during harvest and postharvest have been evaluated. The aim of this study was to evaluate cinnamon essential oil, neem oil, and black sapote fruit extract for in vitro inhibition of fungi isolated from chayote fruit. The extracts were applied at 300, 350, and 400 ppm in Petri dishes and the mycelial growth of Fusarium oxysporum, Fusarium solani, Goetrichum sp., and Phytophthora capsici was evaluated for 7 days, and the percentage of mycelial growth inhibition per day was calculated. Cinnamon oil showed a fungicidal effect at all concentrations. Neem oil at 400 ppm showed a 42.3% reduction in the growth of F. solani and 27.8% reduction in the growth of F. oxysporum, while at 350 ppm it inhibited the mycelial growth of Phytophthora capsici by 53.3% and of Goetrichum sp. by 20.9%; finally, the black sapote extract at 400 ppm inhibited 21.9-28.6% of the growth of all fungi. The growth of postharvest fungi on chayote fruit could be prevented or reduced by applying the plant extracts evaluated at adequate concentrations.

The endophytobiome of wild Rubiaceae as a source of antagonistic fungi against the American Leaf Spot of coffee (Mycena citricolor).

The American leaf spot, caused by Mycena citricolor, is an important disease of coffee (Coffea arabica), mostly in Central America. Currently, there are limited pathogen control alternatives that are environment friendly and economically accessible. The use of fungi isolated from the plant endomycobiota in their native habitats is on the rise because studies show their great potential for biological control. To begin to generate a green alternative to control M. citricolor, the objectives of the present study were to (i) collect, identify, screen (in vitro and in planta), and select endophytic fungi from wild Rubiaceae collected in old-growth forests of Costa Rica; (ii) confirm endophytic colonization in coffee plantlets; (iii) evaluate the effects of the endophytes on plantlet development; and (iv) corroborate the antagonistic ability in planta. Through in vitro and in planta antagonism assays, we found that out of the selected isolates (i.e. Daldinia eschscholzii GU11N, Nectria pseudotrichia GUHN1, Purpureocillium aff. lilacinum CT24, Sarocladium aff. kiliense CT25, Trichoderma rifaii CT5, T. aff. crassum G1C, T. aff. atroviride G7T, T. aff. strigosellum GU12, and Xylaria multiplex GU14T), Trichoderma spp. produced the highest growth inhibition percentages in vitro. Trichoderma isolates CT5 and G1C were then tested in planta using Coffea arabica cv. caturra plantlets. Endophytic colonization was verified, followed by in planta growth promotion and antagonism assays. Results show that Trichoderma isolates CT5 and G1C have potential for plant growth promotion and antagonism against Mycena citricolor, reducing incidence and severity, and preventing plant mortality.

Crystal Structure, Hirshfeld Surface Analysis, and Computational Study of Quinolin-8-yl 4-Chlorobenzoate: Insights from Spectroscopic, Thermal, and Antitumor Properties

We report the time-efficient synthesis of quinolin-8-yl 4-chlorobenzoate (3) via an O-acylation reaction between 8-hydroxyquinoline (1) and 4-chlorobenzoyl chloride (2) mediated by triethylamine in acetonitrile under heating at 80 °C for 20 min in the Monowave 50 reactor. This protocol is distinguished by its short reaction time, operational simplicity, and clean reaction profile. The structure of 3 was fully characterized through a combination of analytical techniques, including NMR, IR, and UV–Vis spectroscopy, MS spectrometry, differential scanning calorimetry (DSC), thermogravimetry (TG), and crystallographic studies. Interestingly, X-ray diffraction analyses of 3 show that the crystal structure is characterized by C-H···N, C-H···O, Cl···π, and π···π interactions. The molecular conformation presents an orthogonal orientation between aromatic rings in the solid state. The calculated interaction energies using the CE-B3LYP model show that dispersion forces act in a higher proportion to build the crystal, which is consistent with the few short hydrogen interactions detected. Electrostatic potential maps suggest the formation of σ-holes over the Cl atoms. Although they can behave as both Lewis acid and base sites, Cl··Cl interactions are absent due to the shallow depth of these σ-holes. Quantum chemical descriptors and global reactivity descriptors were examined using the B3LYP method with the 6-31G(d,p) basis set implemented in CrystalExplorer. Finally, compound 3 exhibited low activity against HOP-92 and EKVX non-Small-cell lung and UO-31 Renal cancer cell lines, with a growth inhibition percentage (GI%) ranging from 6.2% to 18.1%.