Synthesis of novel carbazole hydrazine-carbothioamide scaffold as potent antioxidant, anticancer and antimicrobial agents

BMC Chemistry, Год журнала: 2024, Номер 18(1)

Опубликована: Май 21, 2024

Abstract Background Carbazole-based molecules containing thiosemicarbazide functional groups are recognized for their diverse biological activities, particularly in enhancing therapeutic anticancer effects through inhibiting crucial pathways. These derivatives also exhibit noteworthy antioxidant properties. Objectives This study aims to synthesize, characterize, and evaluate the activities of 18 novel carbazole derivatives. Methods The radical scavenging capabilities compounds were assessed using 2,2-diphenyl-1-picrylhydrazyl assay. Antiproliferative evaluated on MCF-7 cancer cell lines viability assays. Additionally, modulation PI3K/Akt/mTOR pathway, apoptosis/necrosis induction, cycle analysis conducted most promising agents. Results nine showed potent with IC 50 values lower than positive control acarbose, 4 h 4y exhibiting highest potency (IC 0.73 0.38 µM, respectively). Furthermore, 4o 4r displayed significant effects, 2.02 4.99 respectively. Compound , particular, exhibited activity by targeting signaling tumor survival, inducing apoptosis, causing arrest lines. compound was antimicrobial against S. aureus E. coli, antifungal effect C. albicans. Its potential overcome drug resistance this pathway inhibition highlights its promise as an agent. Molecular docking simulations supported these findings, revealing favorable binding profiles interactions within active sites enzymes PI3K, AKT1, mTOR. Moreover, assessing druggability newly synthesized demonstrated optimal physicochemical properties, further endorsing candidates.

Язык: Английский

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Explainable artificial intelligence-assisted virtual screening and bioinformatics approaches for effective bioactivity prediction of phenolic cyclooxygenase-2 (COX-2) inhibitors using PubChem molecular fingerprints

Molecular Diversity, Год журнала: 2024, Номер 28(4), С. 2099 - 2118

Опубликована: Янв. 10, 2024

Язык: Английский

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Bio synthesis, comprehensive characterization, and multifaceted therapeutic applications of BSA-Resveratrol coated platinum nanoparticles

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Апрель 3, 2024

This study examines the manufacturing, characterization, and biological evaluation of platinum nanoparticles, which were synthesized by Enterobacter cloacae coated with Bovine Serum Albumin (BSA) Resveratrol (RSV). The formation PtNPs was confirmed change color from dark yellow to black, due bioreduction chloride E. cloacae. BSA RSV functionalization enhanced these nanoparticles' biocompatibility therapeutic potential. TGA, SEM, XRD, FTIR employed for where drug conjugation-related functional groups studied FTIR. XRD crystalline nature Pt-BSA-RSV NPs, while TGA SEM showed thermal stability post-drug coating morphological changes. Designed composite also found be biocompatible in hemolytic testing, indicating their potential Biomedical applications. After confirmation based nanocaompsite synthesis, they examined anti-bacterial, anti-oxidant, anti-inflammatory, anti-cancer properties. NPs higher concentration-dependent DPPH scavenging activity, measured antioxidant capability. Enzyme inhibition tests demonstrated considerable anti-inflammatory activity against COX-2 15-LOX enzymes. In vitro anticancer studies, effectively killed human ovarian cancer cells. phenomenon facilitated acidic environment cancer, as release assay NP formulation environment. Finally, Molecular docking that has strong an antibacterial, agent. Overall, silico investigations current good medicinal applications designed nanocomposites, however, further in-vivo experiments must conducted validate our findings.

Язык: Английский

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Receptor-based pharmacophore modeling, molecular docking, synthesis and biological evaluation of novel VEGFR-2, FGFR-1, and BRAF multi-kinase inhibitors

BMC Chemistry, Год журнала: 2024, Номер 18(1)

Опубликована: Фев. 23, 2024

Abstract A receptor-based pharmacophore model describing the binding features required for multi-kinase inhibition of target kinases (VEGFR-2, FGFR-1, and BRAF) were constructed validated. It showed a good overall quality in discriminating between active inactive compiled test set compounds with F1 score 0.502 Mathew’s correlation coefficient 0.513. described ligand to hinge region Cys or Ala, glutamate residue Glu-Lys αC helix conserved pair, DFG motif Asp at activation loop, allosteric back pocket next ATP site. Moreover, excluded volumes used define steric extent sites. The application developed virtual screening an in-house scaffold dataset resulted identification benzimidazole-based as promising hit within dataset. Compounds 8a-u designed through structural optimization (un)substituted aryl substitution on 2 5 positions benzimidazole ring. Molecular docking simulations ADME properties predictions confirmed characteristics terms affinity pharmacokinetic properties, respectively. synthesized, they demonstrated moderate potent VEGFR-2 inhibitory activity 10 µM. Compound 8u exhibited against IC 50 values 0.93, 3.74, 0.25 µM, derivatives all selected by NCI (USA) conduct their anti-proliferation screening. 8a 8d mean growth % (GI%) 97.73% 92.51%, Whereas 8h , 8j 8k 8o 8q 8r GI% > 100% (lethal effect). most panel 60 different cancer cell lines progressed further five-dose testing. anticancer tested reaching sub-micromolar range. was found induce cycle arrest MCF-7 line G2/M phase accumulating cells sub-G1 result apoptosis.

Язык: Английский

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Flavonoids and Flavonoid-Based Nanoparticles for Osteoarthritis and Rheumatoid Arthritis Management

BioChem, Год журнала: 2024, Номер 4(1), С. 38 - 61

Опубликована: Март 13, 2024

Arthritis, a global health burden comprising osteoarthritis and rheumatoid arthritis, demands advanced therapeutic approaches. In this context, flavonoids, diverse group of naturally occurring compounds abundant in fruits, vegetables, medicinal plants, have emerged as promising candidates for mitigating the inflammatory processes associated with arthritic conditions. This review aims, first, to provide comprehensive exploration potential focusing on specific such quercetin, epigallocatechin-3-gallate (EGCG), apigenin, luteolin, fisetin, silibinin, kaempferol, naringenin, myricetin. The second section delves into anti-arthritic activities these drawing insights from clinical trials scientific studies. Each flavonoid is scrutinized individually elucidate its mechanisms action efficacy context both arthritis. third highlights challenges harnessing flavonoids anti-inflammatory purposes. Bioavailability limitations pose significant hurdle, prompting innovative strategies use nanoparticles delivery vehicles. response challenges, fourth focuses emerging field flavonoid-based nanoparticles. includes detailed discussions EGCG, naringenin-based nanoparticles, highlighting formulation preclinical evidence supporting their arthritis management. targeted sites synergistic combinations other are also discussed avenues enhance impact flavonoids. consolidates current knowledge nanoformulations interventions By addressing presenting future research directions, aims contribute advancement effective alleviating

Язык: Английский

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Flavonoids and their role in oxidative stress, inflammation, and human diseases

Chemico-Biological Interactions, Год журнала: 2025, Номер unknown, С. 111489 - 111489

Опубликована: Март 1, 2025

Oxidative stress and chronic inflammation are important drivers in the pathogenesis progression of many diseases, such as cancers breast, kidney, lung, others, autoimmune diseases (rheumatoid arthritis), cardiovascular (hypertension, atherosclerosis, arrhythmia), neurodegenerative (Alzheimer's disease, Parkinson's Huntington's disease), mental disorders (depression, schizophrenia, bipolar disorder), gastrointestinal (inflammatory bowel colorectal cancer), other disorders. With increasing demand for less toxic more tolerable therapies, flavonoids have potential to effectively modulate responsiveness conventional therapy radiotherapy. Flavonoids polyphenolic compounds found fruits, vegetables, grains, plant-derived beverages. Six twelve structurally different flavonoid subgroups dietary significance include anthocyanidins (e.g. pelargonidin, cyanidin), flavan-3-ols epicatechin, epigallocatechin), flavonols quercetin, kaempferol), flavones luteolin, baicalein), flavanones hesperetin, naringenin), isoflavones (daidzein, genistein). The health benefits related their structural characteristics, number position hydroxyl groups presence C2=C3 double bonds, which predetermine ability chelate metal ions, terminate ROS radicals formed by Fenton reaction), interact with biological targets trigger a response. Based on these can exert both antioxidant or prooxidant properties, activity ROS-scavenging enzymes expression activation proinflammatory cytokines (e.g., interleukin-1beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)), induce apoptosis autophagy, target key signaling pathways, nuclear factor erythroid 2-related 2 (Nrf2) Bcl-2 family proteins. This review aims briefly discuss mutually interconnected aspects oxidative inflammatory mechanisms, lipid peroxidation, protein oxidation, DNA damage, mechanism resolution inflammation. major part this article discusses role alleviating inflammation, two common components human diseases. results epidemiological studies also presented.

Язык: Английский

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Critical review on anti‐inflammation effects of saponins and their molecular mechanisms

Phytotherapy Research, Год журнала: 2024, Номер 38(4), С. 2007 - 2022

Опубликована: Фев. 19, 2024

Abstract This review highlights the increasing interest in one of natural compounds called saponins, for their potential therapeutic applications addressing inflammation which is a key factor various chronic diseases. It delves into molecular mechanisms responsible anti‐inflammatory effects these amphiphilic compounds, prevalent plant‐based foods and marine organisms. Their structures vary with soap‐like properties influencing historical uses traditional medicine sparking renewed scientific interest. Recent research focuses on inflammatory diseases, unveiling actions such as NF‐κB MAPK pathway regulation COX/LOX enzyme inhibition. Saponin‐containing sources like Panax ginseng soybeans suggest novel therapies. The explores emerging role shaping gut microbiome, composition activity, contributing to effects. Specific examples, notoginseng Gynostemma pentaphyllum , illustrate intricate relationship between collective impact immune metabolic health. Despite promising findings, emphasizes need further comprehend behind interactions underscoring crucial balanced microbiome optimal health positioning saponins dietary interventions managing conditions.

Язык: Английский

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Astaxanthin targets IL-6 and alleviates the LPS-induced adverse inflammatory response of macrophages

Food & Function, Год журнала: 2024, Номер 15(8), С. 4207 - 4222

Опубликована: Янв. 1, 2024

AST exerts anti-inflammatory effects and may target IL-6 to inhibit the positive feedback loop of inflammatory factors, thereby effectively reducing adverse responses.

Язык: Английский

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Metabolic-Associated Fatty Liver Disease: The Influence of Oxidative Stress, Inflammation, Mitochondrial Dysfunctions, and the Role of Polyphenols

Pharmaceuticals, Год журнала: 2024, Номер 17(10), С. 1354 - 1354

Опубликована: Окт. 10, 2024

Metabolic-Associated Fatty Liver Disease (MAFLD) is a clinical-pathological scenario that occurs due to the accumulation of triglycerides in hepatocytes which considered significant cause liver conditions and contributes an increased risk death worldwide. Even though possible causes MAFLD can involve interaction genetics, hormones, nutrition, lifestyle (diet sedentary lifestyle) most influential factor developing this condition. Polyphenols comprise many natural chemical compounds be helpful managing metabolic diseases. Therefore, aim review was investigate impact oxidative stress, inflammation, mitochondrial dysfunction, role polyphenols MAFLD. Some reverse part damage related or among them are anthocyanin, baicalin, catechin, curcumin, chlorogenic acid, didymin, epigallocatechin-3-gallate, luteolin, mangiferin, puerarin, punicalagin, resveratrol, silymarin. These have actions reducing plasma enzymes, body mass index, waist circumference, adipose visceral indices, lipids, glycated hemoglobin, insulin resistance, HOMA index. They also reduce nuclear factor-KB (NF-KB), interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), blood pressure, fat content, steatosis fibrosis. On other hand, they improve HDL-c, adiponectin levels, fibrogenesis markers. results show promising prevention treatment

Язык: Английский

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Anti-Parkinson potential of hesperetin nanoparticles: in vivo and in silico investigations

Natural Product Research, Год журнала: 2024, Номер unknown, С. 1 - 10

Опубликована: Апрель 22, 2024

Parkinson's disease (PD) is characterised by the gradual demise of dopaminergic neurons. In recent years, there has been significant interest in herbal treatments. this study, hesperetin nanoparticles (HTN) were developed and compared their anti-PD potential with (HT) on rotenone induced PD rats. Molecular docking was also performed to evaluate binding affinity pathological protein, i.e. D2 dopamine receptors (DR2), using Auto Dock Vina tools. The results showed a higher relationship HTN (−7.2 kcal/mol) L-dopa (−6.4 kcal/mol), supporting as drug candidates for therapy. effectively synthesised fabrication technique zeta SEM analysis. had favourable characteristics, including size 249.8 ± 14.9 nm Z-potential −32.9 mV. After being administered orally, demonstrated notable anti-Parkinsonian effects, indicated improvement motor function assessed rota rod test (p < .001***), pole stair .01**), wood walk .01**) an increase substantia nigra (SN) antioxidant levels, CAT SOD GSH .01**). Additionally, led increased levels decrease oxidant system, MDA Furthermore, histopathological examination revealed decreased SN neuronal necrosis diseased animals treated those HT rat model disease. Therefore, can be regarded viable platform efficient therapy PD.

Язык: Английский

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