Computational design and in vitro assay of lantadene-based novel inhibitors of NS3 protease of dengue virus DOI Creative Commons
Somdutt Mujwar,

Jyoti Pal,

Manu Sharma

et al.

Open Chemistry, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 1, 2024

Abstract Dengue virus (DENV) infection is one of the diseases for which no drug available treatment. The DENV NS2B-NS3 protease considered to be prime target anti-dengue development because its importance in new subunits via poly-protein breakdown. Pentacyclic triterpenoids (Lantadenes) from weed Lantana camara L. and semi-synthetic congeners have shown a wide array biological activities last two decades. virtual screening strategy was used on library 78 natural lantadenes predict potent antagonists enzyme their experimental validation by vitro assay lead molecules. In silico analysis triterpenoids, molecules (−10.60 −9.93 kcal/mol) were predicted inhibitors (viral) when compared reference ligand 1,8-dihydroxy-4,5-dinitroanthraquinone (−5.377 kcal/mol). At same time, binding affinity, pharmacokinetic, toxicity profiling, along with molecular dynamics simulations, studied. viral inhibition inferred that molecule 62 exhibited 60% 45% reduction titers at 10 5 µM concentrations, respectively. can further optimized pharmacophore has potential developed as drug-like molecule.

Language: Английский

Anti-Cancer Properties of Resveratrol: A Focus on Its Impact on Mitochondrial Functions DOI Creative Commons
Lolita Kuršvietienė, Dalia M. Kopustinskienė,

Inga Stanevičienė

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(12), P. 2056 - 2056

Published: Nov. 29, 2023

Cancer is one of the most serious public health issues worldwide, demanding ongoing efforts to find novel therapeutic agents and approaches. Amid growing interest in oncological applications phytochemicals, particularly polyphenols, resveratrol-a naturally occurring polyphenolic stilbene derivative-has emerged as a candidate interest. This review analyzes pleiotropic anti-cancer effects resveratrol, including its modulation apoptotic pathways, cell cycle regulation, inflammation, angiogenesis, metastasis, interaction with cancer stem cells tumor microenvironment. The resveratrol on mitochondrial functions, which are crucial development, also discussed. Future research directions identified, elucidation specific molecular targets, facilitate clinical translation prevention therapy.

Language: Английский

Citations

30
Allium cepa bioactive phytochemicals as potent ALK (Anaplastic lymphoma kinase) inhibitors and therapeutic agents against non-small cell lung cancer (NSCLC): a computational Study DOI
Md. Sakib Al Hasan,

Emon Mia,

Noshin Tasnim Yana

et al.

Pharmacological Research - Natural Products, Journal Year: 2024, Volume and Issue: unknown, P. 100124 - 100124

Published: Nov. 1, 2024

Language: Английский

Citations

8
Normalization of tumor vasculature by imiquimod: proposal for a new anticancer therapeutic indication for a TLR7 agonist DOI Creative Commons

Jarosz-Biej Magdalena,

Czapla Justyna,

C Renshaw Joanna

et al.

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(3)

Published: Feb. 1, 2025

Imiquimod (IMQ), a drug from aminoquinoline group, is the toll-like receptor 7 (TLR7) agonist. It acts as an immunostimulant and radio-sensitizing agent. IMQ stimulates both innate adaptive immune response. Despite studies conducted, there are no unambiguous data showing how affects condition of tumor blood vessels. Tumor vasculature plays main role in progression. Formation abnormal vessels increases area hypoxia which recruits suppressor cells, blocks infiltration by CD8+ T lymphocytes, inhibits efficacy chemoterapeutic leads to cancer relapse. Normalization type therapy targeted at Here, we demonstrated that 50 µg growth melanoma tumors more efficiently, compared other tested doses control group. Dose escalation did not improve therapeutic antitumor potential TLR7 A dose most effectively reduced vessel density. normalized structurally (by reducing tortuosity increasing pericyte coverage) functionally improving perfusion) dose-dependent manner. Hypoxia regions treated mice were significantly after administration. had also greatest impact on changes tumor-infiltrating lymphocytes levels. agonist inhibited angiogenesis mice. Functional vascular normalization effectiveness low doxorubicin. Higher showed worse effects than lower including decreased perfusion, increased immunosuppression. This knowledge may help optimize combination selected with e.g. chemotherapy or radiotherapy elicit synergistic effect treatment. To conclude, outline repurposing normalizing Our research results contribute expanding indications for use anticancer future.

Language: Английский

Citations

1
Tomatidine targets ATF4-dependent signaling and induces ferroptosis to limit pancreatic cancer progression DOI Creative Commons
Debasmita Mukherjee,

Srija Chakraborty,

Lena Bercz

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(8), P. 107408 - 107408

Published: July 17, 2023

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with high metastasis and therapeutic resistance. Activating transcription factor 4 (ATF4), a master regulator of cellular stress, exploited by cells to survive. Prior research data reported provide evidence that ATF4 expression correlates worse overall survival in PDAC. Tomatidine, natural steroidal alkaloid, associated inhibition signaling multiple diseases. Here, we discovered vitro vivo tomatidine treatment PDAC inhibits tumor growth. Tomatidine inhibited nuclear translocation reduced the transcriptional binding downstream promoters. enhanced gemcitabine chemosensitivity 3D ECM-hydrogels vivo. was induction ferroptosis validated increased lipid peroxidation, mitochondrial biogenesis, decreased GPX4 cells. This study highlights possible approach utilizing plant-derived metabolite, tomatidine, target activity

Language: Английский

Citations

17
Therapeutic Potential of Plant-Derived Compounds and Plant Extracts in Rheumatoid Arthritis—Comprehensive Review DOI Creative Commons
Mateusz Kciuk, Anjali Garg, Manni Rohilla

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(7), P. 775 - 775

Published: June 27, 2024

Rheumatoid arthritis (RA) is a persistent autoimmune disorder that characterized by joint inflammation, discomfort, and impairment. Despite the existence of several therapeutic approaches, their effectiveness often restricted may be linked to unfavorable side effects. Consequently, there has been growing interest in investigating naturally derived compounds as plausible agents for RA disease. The objective this review summarize existing preclinical clinical evidence regarding efficacy extracted plant extracts treatment RA, focusing on anti-inflammatory, anti-oxidative, immunomodulatory properties. Some problems with using natural chemicals are uneven quality commercially available preparations poor bioavailability these compounds. Future investigations should focus improving formulations, conducting thorough trials, exploring different techniques fully utilize intrinsic potential treating RA.

Language: Английский

Citations

7
Exploring the Comprehensive Neuroprotective and Anticancer Potential of Afzelin DOI Creative Commons
Mateusz Kciuk, Nitika Garg, Sanchit Dhankhar

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(6), P. 701 - 701

Published: May 28, 2024

Neurodegenerative diseases (Alzheimer’s disease, Parkinson’s Huntington’s and others) cancer, seemingly disparate in their etiology manifestation, exhibit intriguing associations certain cellular molecular processes. Both cancer neurodegenerative involve the deregulation of processes such as apoptosis, proliferation, DNA repair pose a significant global health challenge. Afzelin (kaempferol 3-O-rhamnoside) is flavonoid compound abundant various plant sources. exhibits diverse range biological activities, offering promising prospects for treatment hallmarked by oxidative stress cell death pathways. Its protective potential against also alleviating side effects chemotherapy. This review explores therapeutic implications afzelin, including its capacity to mitigate stress, modulate inflammation, promote regeneration diseases.

Language: Английский

Citations

6
Biodegradable Persistent Luminescence Nanoparticles as Pyroptosis Inducer for High‐Efficiency Tumor Immunotherapy DOI Creative Commons
Lin Liu, Junpeng Shi, Jin‐Yuan Wang

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(39)

Published: Aug. 19, 2024

Abstract Pyroptosis possesses potent antitumor immune activity, making pyroptosis inducer development a promising direction for tumor immunotherapy. Persistent luminescence nanoparticles (PLNPs) are highly sensitive optical probes extensively employed in diagnosis and therapy. However, based on PLNPs has not been reported yet. Herein, polyethylene glycol–poly lactic acid‐co‐glycolic acid (PEG–PLGA: PP) modified biodegradable CaS:Eu 2+ (CSE@PP) synthesized as immunotherapy the first time. The CSE@PP biowindow persistent (PersL) pH‐responsive degradation properties, allowing it to remain stable under neutral pH but degrade when exposed weak (pH < 6.5). During within tumor, constantly releases H 2 S Ca while its PersL gradually fades away. Thus, signal can self‐monitor release. Furthermore, released result mitochondrial dysfunction inactivation of reactive oxygen species scavenging enzymes, synergistic facilitating intracellular oxidative stress, which induces caspase‐1/GSDM‐D dependent subsequent responses. In word, is confirmed that release pyroptosis‐mediated Immunotherapy. This work will facilitate biomedical applications inspire pyroptosis‐induced

Language: Английский

Citations

5
In-silico investigation of alpha-bisabolol and derivatives as inhibitors of bcl-2 family proteins for targeting glioblastoma DOI Creative Commons
Nilüfer Vural, Sibel Kaymak

International Journal of Secondary Metabolite, Journal Year: 2025, Volume and Issue: 12(1), P. 1 - 15

Published: Jan. 19, 2025

Glioblastoma is one of the most common and destructive types tumors, with an increasing number around world. Alpha-bisabolol a plant secondary metabolite discovered anticancer activity, which can also be considered potential treatment for glioblastoma. In silico investigations provide adequate information understanding roles alpha-bisabolol compounds in For this purpose, computational drug design procedures were applied to investigate anti-glioblastoma biotherapeutic compounds. study, bcl-2 family proteins' inhibitory activity their toxicity properties investigated by molecular docking studies. Toxicity evaluated prediction tools as, CarcinoPred carcinogenicity LAZAR mutagenicity, pkCSM, SwissADME absorption, distribution, metabolism, excretion (ADMET) analysis BOILED-Egg model, PASS analyze biological functions druggability, DruLiTo program compute likeness property QSAR Toolbox modeling. The results reveal oxide B, alpha bisabolol derivative, glioblastoma mechanisms proteins, being non-toxic non-mutagenic.

Language: Английский

Citations

0
Modification in Structures of Active Compounds in Anticancer Mitochondria-Targeted Therapy DOI Open Access
Agnieszka Felczykowska, Anna Herman-Antosiewicz

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1376 - 1376

Published: Feb. 6, 2025

Cancer is a multifaceted disease characterised by uncontrolled cellular proliferation and metastasis, resulting in significant global mortality. Current therapeutic strategies, including surgery, chemotherapy, radiation therapy, face challenges such as systemic toxicity tumour resistance. Recent advancements have shifted towards targeted therapies that act selectively on molecular structures within cancer cells, reducing off-target effects. Mitochondria emerged pivotal targets this approach, given their roles metabolic reprogramming, retrograde signalling, oxidative stress, all of which drive the malignant phenotype. Targeting mitochondria offers promising strategy to address these mechanisms at origin. Synthetic derivatives natural compounds hold particular promise mitochondrial-targeted therapies. Innovations drug design, use conjugates nanotechnology, focus optimizing for mitochondrial specificity. Such enhance efficacy while minimizing toxicity, presenting step forward modern anticancer strategies.

Language: Английский

Citations

0
Antitumor Activity, Mechanisms of Action and Phytochemical Profiling of Sub-Fractions Obtained from Ulex gallii Planch. (Fabaceae): A Medicinal Plant from Galicia (Spain) DOI Creative Commons
Lucía Bada, Hussain Shakeel Butt, Elías Quezada

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(4), P. 972 - 972

Published: Feb. 19, 2025

The plant kingdom serves as a valuable resource for cancer drug development. This study explored the antitumor activity of different sub-fractions (hexane, dichloromethane and methanol) U. gallii (gorse) methanol extract in glioblastoma (U-87MG U-373MG) neuroblastoma (SH-SY5Y) cell lines, along with their phytochemical profiles. Cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) lactate dehydrogenase (LDH) assays, cycle arrest apoptosis were assessed through flow cytometry by measuring reactive oxygen species (ROS) protein expression levels. D7 D8 significantly reduced viability, triggered early SH-SY5Y U-87MG cells specifically increased ROS levels cells. Western blot analyses showed that p53, caspase-3, caspase-8 γH2AX cells, while elevated p53 caspase-3 both lines. In U-373 markedly inducing necrosis. Morphological changes indicative also observed all Bioinformatic analysis UHPLC-MS GC-MS data tentatively identified 20 metabolites 15 D8, primarily flavonoids. HPLC-DAD confirmed isoprunetin genistein most abundant respectively, isolated NMR spectroscopy. Most flavonoids have been reported agents, suggesting these compounds may be responsible pharmacological activity.

Language: Английский

Citations

0