Investigation of the Potential Targets behind the Promising and Highly Selective Antileishmanial Action of Synthetic Flavonoid Derivatives DOI
Estela Mariana Guimarães Lourenço,

Fernanda da Silva,

Amarith R. das Neves

et al.

ACS Infectious Diseases, Journal Year: 2023, Volume and Issue: 9(10), P. 2048 - 2061

Published: Sept. 29, 2023

Leishmaniases are among the neglected tropical diseases that still cause devastating health, social, and economic consequences to more than 350 million people worldwide. Despite efforts combat these vector-borne diseases, their incidence does not decrease. Meanwhile, current antileishmanial drugs old highly toxic, safer presentations unaffordable most severely affected human populations. In a previous study by our research group, we synthesized 17 flavonoid derivatives demonstrated impressive inhibition capacity against rCPB2.8, rCPB3, rH84Y. These cysteine proteases expressed in amastigote stage, target form of parasite. However, although compounds have been already described literature, until now, effect any molecules has proven. this work, aimed deeply analyze action set synthetic correlating ability inhibit with Among all derivatives, 11 them showed high activity amastigotes Leishmania amazonensis, also providing safety mammalian host cells. Furthermore, production nitric oxide infected cells treated active protease B (CPB) inhibitors confirms potential immunomodulatory response macrophages. Besides, considering flavonoids as multitarget drugs, investigated other mechanisms. The were selected investigate another biological pathway behind using flow cytometry analysis. results confirmed an oxidative stress after 48 h treatment. data represent important step toward validation CPB target, well aiding new drug discovery studies based on protease.

Language: Английский

Role of NLRP3 inflammasome in central nervous system diseases DOI Creative Commons
Lu Zhang, Yufen Tang, Peng Huang

et al.

Cell & Bioscience, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 7, 2024

Abstract The central nervous system (CNS) is the most delicate in human body, with complex structure and function. It vulnerable to trauma, infection, neurodegeneration autoimmune diseases, activates immune system. An appropriate inflammatory response contributes defence against invading microbes, whereas an excessive can aggravate tissue damage. NLRP3 inflammasome was first one studied brain. Once primed activated, it completes assembly of (sensor NLRP3, adaptor ASC, effector caspase-1), leading caspase-1 activation increased release downstream cytokines, as well pyroptosis. Cumulative studies have confirmed that plays important role regulating innate immunity its inhibitors shown good efficacy animal models various diseases. In this review, we will briefly discuss biological characteristics inflammasome, summarize recent advances clinical impact infectious, inflammatory, immune, degenerative, genetic, vascular diseases CNS, potential challenges a therapeutic target for CNS

Language: Английский

Citations

12
Recent Advances in the Synthesis and Antioxidant Activity of Low Molecular Mass Organoselenium Molecules DOI Creative Commons
João M. Anghinoni, Paloma T. Birmann, Marcia Juciele da Rocha

et al.

Molecules, Journal Year: 2023, Volume and Issue: 28(21), P. 7349 - 7349

Published: Oct. 30, 2023

Selenium is an essential trace element in living organisms, and present selenoenzymes with antioxidant activity, like glutathione peroxidase (GPx) thioredoxin reductase (TrxR). The search for small selenium-containing molecules that mimic a strong field of research organic medicinal chemistry. In this review, we review the synthesis bioassays new known organoselenium compounds covering last five years. A detailed description synthetic procedures performed vitro vivo presented, highlighting most active each series.

Language: Английский

Citations

18
Recent drug design strategies and identification of key heterocyclic scaffolds for promising anticancer targets DOI
Alia Mushtaq, Peng Wu, Muhammad Moazzam Naseer

et al.

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 254, P. 108579 - 108579

Published: Dec. 30, 2023

Language: Английский

Citations

15
B(C6F5)3-catalyzed selective C–H chalcogenation of arenes and heteroarenes DOI Creative Commons
Milan Pramanik,

Sampurna Das,

Rasool Babaahmadi

et al.

Chem, Journal Year: 2024, Volume and Issue: 10(9), P. 2901 - 2915

Published: June 27, 2024

The synthesis of organochalcogenides remains a valuable area research due to their widespread biological applications, particularly in pharmaceuticals. Herein, our study details the B(C6F5)3-catalyzed Csp2–H functionalization diverse arenes, heteroarenes, and pharmacophores with thiosuccinimides or selenosuccinimides, providing selective access chalcogenated products. This protocol enables late-stage chalcogenation drug molecules such as anti-inflammatory naproxen, estrogen steroid hormone estradiol derivatives, industrially relevant trifluoromethylthiolation reaction. Furthermore, this C–S coupling methodology provides facile metal-free route synthesize vortioxetine, an antidepressant drug, plethora significant organic motifs. Detailed NMR, EPR analyses, density functional theory (DFT) computational studies indicate that elongation thiosuccinimide N–S bond is assisted by boron-centered adduct, which then leads stable ion pair arene. analysis shows transient radical pair, potentially off-cycle species, not directly involved catalytic process.

Language: Английский

Citations

5
Versatile Electrochemical Synthesis of Selenylbenzo[b]Furan Derivatives Through the Cyclization of 2-Alkynylphenols DOI Creative Commons

Carlos V. Doerner,

Marcos R. Scheide, Celso R. Nicoleti

et al.

Frontiers in Chemistry, Journal Year: 2022, Volume and Issue: 10

Published: May 17, 2022

We report an electrochemical oxidative intramolecular cyclization reaction between 2-alkynylphenol derivatives and different diselenides species to generate a wide variety of substituted-benzo[b]furans. Driven by the galvanostatic electrolysis assembled in undivided cell, it provided efficient transformation into oxidant-, base-, metal-free conditions open system at room temperature. With satisfactory functional group compatibility, products were obtained good excellent yields.

Language: Английский

Citations

22
Temozolomide Resistance in Glioblastoma by NRF2: Protecting the Evil DOI Creative Commons

Karoline Almeida Lima,

Isabeli Yumi Araújo Osawa, Maria Carolina Clares Ramalho

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(4), P. 1081 - 1081

Published: April 3, 2023

The transcription factor NRF2 is constitutively active in glioblastoma, a highly aggressive brain tumor subtype with poor prognosis. Temozolomide (TMZ) the primary chemotherapeutic agent for this type of treatment, but resistance to drug often observed. This review highlights research that demonstrating how hyperactivation creates an environment favors survival malignant cells and protects against oxidative stress TMZ. Mechanistically, increases detoxification, autophagy, DNA repair, decreases accumulation apoptotic signaling. Our also presents potential strategies targeting as adjuvant therapy overcome TMZ chemoresistance glioblastoma. Specific molecular pathways, including MAPKs, GSK3β, βTRCP, PI3K, AKT, GBP, modulate expression leading are discussed, along importance identifying modulators reverse develop new therapeutic targets. Despite significant progress understanding role GBM, there still unanswered questions regarding its regulation downstream effects. Future should focus on elucidating precise mechanisms by which mediates TMZ, novel targets intervention.

Language: Английский

Citations

12
Selenylated Imidazo[1,2-a]pyridine Induces Cell Senescence and Oxidative Stress in Chronic Myeloid Leukemia Cells DOI Creative Commons

Gabriella Teles Burkner,

Dhébora Albuquerque Dias, Kamylla Fernanda Souza de Souza

et al.

Molecules, Journal Year: 2023, Volume and Issue: 28(2), P. 893 - 893

Published: Jan. 16, 2023

Imidazo[1,2-a]pyridines (IPs) have been studied regarding drug development. The objective of this work was to evaluate the antileukemic capacity IP derivatives by screening their ability as a pro-oxidant. were synthesized and oral bioavailability toxicity analyzed in silico. Redox performed on human Kasumi, KG-1, K562, Jurkat leukemia cells. derivative most responsive leukemic cell selected for cytotoxicity, proliferation, senescence, oxidative stress assays. predictive analysis showed possible effect reproductive system, but without mutagenic, carcinogenic, or irritability effects. MRK-107 against K562 cells compound that best redox profile. did not induce death monocyte However, able decrease proliferation increase senescence after 48 72 h. Furthermore, induced h, increasing lipid peroxidation decreasing reduced glutathione (GSH) contents. This study demonstrated MRK-107-induced with involvement is mechanism action, addressing potential antitumor chronic myeloid leukemia.

Language: Английский

Citations

11
Urea Hydrogen Peroxide and Ethyl Lactate, an Eco-Friendly Combo System in the Direct C(sp2)–H Bond Selenylation of Imidazo[2,1-b]thiazole and Related Structures DOI Creative Commons
Cassio A. O. Moraes,

Rafaely B. C. Santos,

Marcos F. O. Cavalcante

et al.

ACS Omega, Journal Year: 2023, Volume and Issue: 8(42), P. 39535 - 39545

Published: Oct. 12, 2023

Herein, we describe a urea hydrogen peroxide-mediated sustainable protocol for the synthesis of selenylated imidazo[2,1-b]thiazole by using half molar equivalent diorganyl diselenides in ethyl lactate as greener solvent. The reaction features high yields, easy performance on gram scale, metal-free conditions, well applicability to imidazopyridine and imidazopyrimidine.

Language: Английский

Citations

11
Naphthalene peri-Diselenide-Based BODIPY Probe for the Detection of Hydrogen Peroxide, tert-Butylhydroperoxide, Hydroxyl Radical, and Peroxynitrite Ion DOI Creative Commons

Babli Chhillar,

Nikhil Sodhi,

Rajni Kadian

et al.

ACS Omega, Journal Year: 2025, Volume and Issue: 10(7), P. 6396 - 6405

Published: Feb. 13, 2025

Dimethoxynaphthalene peri-diselenide-based BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) probe has been synthesized. The demonstrated selectivity and sensitivity for hydrogen peroxide (H2O2) tert-butylhydroperoxide (t-BuOOH), hydroxyl radical (•OH), peroxynitrite ion (ONOO–) detection reversibility upon treatment with glutathione. limits of the were observed to be 0.40 μM H2O2, 0.41 t-BuOOH, 0.95 •OH, 0.46 ONOO–, respectively. A proposed mechanism "turn-on" event suggested corroborated by spectroscopic computational data. It that electron transfer occurred from Se center moiety, followed photoinduced (PET) mechanism.

Language: Английский

Citations

0
Editorial: Targeting cellular signalling pathways for disease therapy: the potential of cellular reprogramming and protein kinase inhibitors DOI Creative Commons
Vanessa Marensi, Pedro F. Oliveira, Ariane Zamoner

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 19, 2025

Cellular reprogramming is particularly active during development, regeneration and cancer, when dynamic signaling pathways orchestrate cellular changes in response to input signals (1). It facilitates adaptation exogenous pressure enabling tumor cells adapt survive adverse microenvironments (2,3). Understanding the mechanism these adaptations happen has fueled significant advances medical science, regenerative medicine targeted cancer therapies (4,5). Spatialtemporal integration of fundamental effective reprogramming.Dysregulation protein kinases key pathogenesis various pathologies, dictating disease progression inhibitors targeting this family represent pivotal tools modern therapeutics (6). Transduction via MAPK PI3K pathway been extensively studied stablished as mediator (7).Molecules like providing tailored have already approved for clinical applications (8,9). Despite advances, cross-communication between occurs further understanding needed uncover rewiring develops (7). This research topic focuses on cascades result reprograming their target therapeutic strategy consolidates recent advancements how are modulated purposes. The studies included here provide a comprehensive overview some aspects developments field summarized

Language: Английский

Citations

0