Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: in-vitro anticancer evaluation and in-silico studies

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 37(1), P. 1903 - 1917

Published: July 8, 2022

A thiazolidine-2,4-dione nucleus was molecularly hybridised with the effective antitumor moieties; 2-oxo-1,2-dihydroquinoline and 2-oxoindoline to obtain new hybrids potential activity against VEGFR-2. The cytotoxic effects of synthesised derivatives Caco-2, HepG-2, MDA-MB-231 cell lines were investigated. Compound 12a found be most potent candidate investigated IC50 values 2, 10, 40 µM, respectively. Furthermore, tested in vitro for their VEGFR-2 inhibitory showing strong inhibition. Moreover, an viability study Vero non-cancerous line results reflected a high safety profile all compounds. further its apoptotic behaviour by assessing gene expression four genes (Bcl2, Bcl-xl, TGF, Survivin). Molecular dynamic simulations authenticated affinity, accurate binding, perfect dynamics compound

Language: Английский

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The rapid discovery, target preparation, and bioactivity evaluation of 5-lipoxygenase and acetylcholinesterase inhibitors from the flowers of Astragalus membranaceus (Fisch) Bge

Industrial Crops and Products, Journal Year: 2025, Volume and Issue: 225, P. 120504 - 120504

Published: Jan. 11, 2025

Language: Английский

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The importance of method validation in herbal drug research

Journal of Pharmaceutical and Biomedical Analysis, Journal Year: 2022, Volume and Issue: 214, P. 114735 - 114735

Published: March 23, 2022

Language: Английский

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New quinoline and isatin derivatives as apoptotic VEGFR-2 inhibitors: design, synthesis, anti-proliferative activity, docking, ADMET, toxicity, and MD simulation studies

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 37(1), P. 2191 - 2205

Published: Aug. 16, 2022

New quinoline and isatin derivatives having the main characteristics of VEGFR-2 inhibitors was synthesised. The antiproliferative effects these compounds were estimated against A549, Caco-2, HepG2, MDA-MB-231. Compounds 13 14 showed comparable activities with doxorubicin Caco-2 cells. These strongly inhibited kinase activity. cytotoxic evaluated Vero Compound 7 highest value safety selectivity. Cell migration assay displayed ability compound to prevent healing abilities in cancer Furthermore, induced apoptosis through expressive down-regulation apoptotic genes, Bcl2, Bcl-xl, Survivin, upregulation TGF gene. Molecular docking emerged interactions synthesised a similar way sorafenib. Additionally, seven molecular dynamics simulations studies applied confirmed stability active pocket over 100 ns.

Language: Английский

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Robust antiviral activity of commonly prescribed antidepressants against emerging coronaviruses: in vitro and in silico drug repurposing studies

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: July 28, 2022

Abstract During the current coronavirus disease 2019 (COVID-19) pandemic, symptoms of depression are commonly documented among both symptomatic and asymptomatic quarantined COVID-19 patients. Despite that many FDA-approved drugs have been showed anti-SARS-CoV-2 activity in vitro remarkable efficacy against clinical trials, no pharmaceutical products yet declared to be fully effective for treating COVID-19. Antidepressants comprise five major drug classes treatment depression, neuralgia, migraine prophylaxis, eating disorders which frequently reported Herein, eight prescribed antidepressants on inhibition SARS-CoV-2 MERS-CoV was assessed. Additionally, anti-MERS-CoV activities were evaluated. Furthermore, molecular docking studies performed these spike (S) main protease (M pro ) pockets MERS-CoV. Results Amitriptyline, Imipramine, Paroxetine, Sertraline had potential anti-viral activities. Our findings suggested aforementioned deserve more vivo targeting especially those patients suffering from depression.

Language: Английский

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Traditional and Computational Screening of Non-Toxic Peptides and Approaches to Improving Selectivity

Pharmaceuticals, Journal Year: 2022, Volume and Issue: 15(3), P. 323 - 323

Published: March 8, 2022

Peptides have positively impacted the pharmaceutical industry as drugs, biomarkers, or diagnostic tools of high therapeutic value. However, only a handful progressed to market. Toxicity is one main obstacles translating peptides into clinics. Hemolysis hemotoxicity, principal source toxicity, natural disease-induced event leading death vital red blood cells. Initial screenings for toxicity been widely evaluated using erythrocytes gold standard. More recently, many online databases filled with peptide sequences and their biological meta-data paved way toward hemolysis prediction user-friendly, fast-access machine learning-driven programs. This review details growing contributions in silico approaches developed last decade large-scale erythrocyte lysis induced by peptides. After an overview landscape therapeutics, we highlighted relevance early studies drug development. We emphasized computational models algorithms used this end light historical recent findings promising field. benchmarked seven predictors from different data sets, having 7–35 amino acids length. According our predictions, scored accuracy over 50.42% minimal Matthew’s correlation coefficient 0.11. The maximum values these statistical parameters achieved 100.0% 1.00, respectively. Finally, strategies optimizing selectivity were described, well prospects future investigations. development predictive has just started, but important clearly demonstrate potential science computer-aided design. Methodology refinement increasing use will motivate timely accurate identification selective, non-toxic therapeutics.

Language: Английский

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Bioactive Azadirachta indica and Melia azedarach leaves extracts with anti-SARS-CoV-2 and antibacterial activities

PLoS ONE, Journal Year: 2023, Volume and Issue: 18(3), P. e0282729 - e0282729

Published: March 8, 2023

The leaves of Azadirachta indica L. and Melia azedarach L., belonging to Meliaceae family, have been shown medicinal benefits are extensively employed in traditional folk medicine. Herein, HPLC analysis the ethyl acetate fraction total methanolic extract emphasized enrichment both A . M extracts with phenolic flavonoids composites, respectively. Besides, 4 limonoids 2 were isolated using column chromatography. By assessing vitro antiviral activities against Severe Acute Respiratory Syndrome Corona virus (SARS-CoV-2), it was found that robust anti-SARS-CoV-2 at low half-maximal inhibitory concentrations (IC 50 ) 8.451 6.922 μg/mL, Due high safety cytotoxic (CC 446.2 351.4 μg/ml, respectively, displayed extraordinary selectivity indices (SI>50). could induce antibacterial Gram-negative positive bacterial strains. minimal varied from 25 100 mg/mL within 30 min contact time towards tested bacteria. Our findings confirm broad-spectrum value extracts. Finally, additional vivo investigations highly recommended anti-COVID-19 antimicrobial plant

Language: Английский

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Production and characterization of rhamnolipids by Pseudomonas aeruginosa isolated in the Amazon region, and potential antiviral, antitumor, and antimicrobial activity

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 12, 2024

Abstract Biosurfactants encompass structurally and chemically diverse molecules with surface active properties, a broad industrial deployment, including pharmaceuticals. The interest is growing mainly for the low toxicity, biodegradability, production from renewable sources. In this work, optimized biosurfactant by Pseudomonas aeruginosa BM02, isolated soil of mining area in Brazilian Amazon region was assessed, addition to its antiviral, antitumor, antimicrobial activities. optimal conditions were determined using factorial design, which showed best yield (2.28 mg/mL) at 25 °C, pH 5, 1% glycerol. obtained characterized as mixture rhamnolipids virucidal properties against Herpes Simplex Virus, Coronavirus, Respiratory Syncytial Gram-positive bacteria ( Staphylococcus aureus Enterococcus faecium ), 50 µg/mL. antitumor activity BS (12.5 µg/mL) also demonstrated, potential selectivity reducing proliferation breast tumor cells, after 1 min exposure. These results demonstrate importance studying interconnection between cultivation industrially important compounds, such rhamnolipid-type P. promising sustainable alternative development new prototypes.

Language: Английский

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A promising antifungal lipopeptide from Bacillus subtilis: its characterization and insight into the mode of action

Applied Microbiology and Biotechnology, Journal Year: 2024, Volume and Issue: 108(1)

Published: Jan. 22, 2024

Language: Английский

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Brazilian Stingless Bee Geopropolis Exhibits Antioxidant Properties and Anticancer Potential Against Hepatocellular Carcinoma Cells

Antioxidants, Journal Year: 2025, Volume and Issue: 14(2), P. 141 - 141

Published: Jan. 24, 2025

Hepatocellular carcinoma (HCC) is the third most common cancer in terms of mortality and sixth incidence worldwide. Treatment varies by tumor stage, but low survival rates are across all stages. Due to these poor outcomes, there a critical need for new treatment options lead compounds, prompting an active search. Geopropolis has been identified as source bioactive compounds with various pharmacological activities, including anticancer effects against different types cancer. Since stingless bees may be selective native botanical species, geopropolis they produce can have unusual chemical profile. In this study, we report antioxidant properties potential extracts produced Melipona bicolor, M. marginata, mondury using 2D- 3D- cell culture models. The profile samples UPLC-QTOF HRMS/MS indicated ferreirin dihydrokaempferide main flavonoids, along cupressic acid 15-acetoxyisocupressic abundant diterpenoids. Interestingly, artepillin C, component green propolis, was also detected. showed good viability inhibition selectivity indices comparison cisplatin used HCC option. capacity high correlated cytotoxic effect cells. Investigations into mechanisms show ability induce apoptosis suppress clonogenic lines. We observed spheroid formation, viability, morphology alterations. This first time described panel

Language: Английский

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