Multidrug Resistance Reversed by Maleimide Interactions. A Biological and Synthetic Overview for an Emerging Field DOI
Edson D. Hernández‐Velázquez, Angélica Judith Granados‐López, Jesús Adrián López

et al.

ChemBioChem, Journal Year: 2024, Volume and Issue: 26(1)

Published: Oct. 9, 2024

Abstract Multidrug Resistance (MDR) can be considered one of the most frightening adaptation types in bacteria, fungi, protozoa, and eukaryotic cells. It allows organisms to survive attack many drugs used daily basis. This forces development new more complex, highly specific fight diseases. Given high usage medicaments, poor variation active chemical cores, self‐medication, appearance MDR is frequent each time, has been established as a serious medical social problem. Over years it possible identification several genes proteins responsible for with that blockers them reach reversion try avoid global These mechanisms also have observed cancer cells, calcium channel successful reversion, maleimide found included them. In this review, we explore particularly tree main involved chemoresistance, MRP1 (encoded by ABCC1), BCRP ABCG2) P‐gp ABCB1). The participation remarkably important, aspects its regulations are discussed. Additionally, address history, mechanisms, efforts, specifically focused on synthesis MDR‐reversers co‐administration, well how their biological applications imperative expand available information very plausible source.

Language: Английский

Targeting Neutrophil Extracellular Traps in Gouty Arthritis: Insights into Pathogenesis and Therapeutic Potential DOI Creative Commons

Cantao Li,

Chenxi Wu,

Fenfen Li

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 1735 - 1763

Published: March 1, 2024

Gouty arthritis (GA) is an immune-mediated disorder characterized by severe inflammation due to the deposition of monosodium urate (MSU) crystals in joints. The pathophysiological mechanisms GA are not yet fully understood, and therefore, identification effective therapeutic targets paramount importance. Neutrophil extracellular traps (NETs), intricate structure DNA scaffold, encompassing myeloperoxidase, histones, elastases - have gained significant attention as a prospective target for gouty arthritis, their innate antimicrobial immunomodulatory properties. Hence, exploring potential NETs remains enticing avenue further investigation. During process formation triggers release inflammatory cytokines, thereby contributing response, while MSU cytokines sequestered degraded aggregation NETs. Here, we provide concise summary processes underlying initiation resolution mediated Furthermore, this review presents overview current pharmacological approaches treating summarizes natural synthetic product-based inhibitors that NET novel options, alongside elucidating intrinsic challenges these research. Lastly, limitations HL-60 cell suitable substitute neutrophils research summarized discussed. Series recommendations provided, strategically oriented towards guiding future investigations effectively address concerns. These findings will contribute enhanced comprehension interplay between GA, facilitating proposition innovative strategies management GA.

Language: Английский

Citations

8
Synthesis and Anti‐inflammatory Effect of Simple 2,3‐Diarylindoles. On Route to New NSAID Scaffolds DOI
Luis A. Segura‐Quezada, Clara Alba Betancourt, Luis Chacón‐García

et al.

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(4)

Published: Jan. 22, 2024

Abstract Nitrogen‐containing drugs represent one of the worldwide most extensive sources treatments for different diseases. Indomethacin as example, is important non‐steroidal anti‐inflammatories (NSAID) indol‐containing drug. Its relevance has been demonstrated last 50 years with excellent pharmacological results. efficacy an anti‐inflammatory treatment, inspired us exploration structurally less elaborated compounds which kept and/or improve activity compared indomethacin. Herein summarized and discussed our initial findings on synthesis effect 2,3‐diarylindoles, designed strategically favoring plausible selective interactions COX‐2, route to new simple NSAID scaffolds. The TPA model formalin test were used in this study generate inflammation mice conducting assays synthesized 2,3‐diarylindoles. Docking analysis revealed stronger N−H indolic COX‐2 6‐methoxy‐2‐phenyl‐3‐(4‐chlorophenyl)‐1 H ‐indole, active when This, experimentally match observed putatively indicates biochemical action mechanism.

Language: Английский

Citations

4
The potential of novel arsenic nanoparticles containing metformin (MTF@As NPs): a study on their antioxidant and cytotoxic properties DOI Creative Commons
Mohammad Reza Shakibaie, Seyed Soheil Hosseininasab,

Soudabe Riahi-Madvar

et al.

BMC Chemistry, Journal Year: 2025, Volume and Issue: 19(1)

Published: March 28, 2025

In the present research, arsenic nanoparticles containing metformin (MTF@As NPs) were synthesized by subjecting a mixture of As2O3 and sodium borohydride solution to microwave irradiation in presence metformin. The physicochemical properties prepared analyzed using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), energy-dispersive X-ray (EDS), scanning electron microscopy (SEM). assessed for their antioxidant potential, hemocompatibility, cytotoxic effects. Based on study's findings, it was found that MTF@As NPs have size range 14–38 nm. DPPH scavenging iron-reducing assays demonstrated exhibited significantly higher activity than As (80–1280 µg/mL). study also revealed compatible materials did not induce significant hemolysis RBCs. According study, concentration required death half cells (IC50) treated with after 24 h be 33.5 ± 2.6 µg/mL 5.7 0.3 MCF-7, NIH3T3 cells, respectively. Notably, toxicity against MCF-7 at concentrations (40–1280 This provides insights into NPs, additional investigation is necessary fully understand these nanoparticles' underlying biological mechanisms.

Language: Английский

Citations

0
Synthesis and Biological Evaluation of Strong Cytotoxic Maleimide Derivatives with Potential Multidrug Resistance Reversal Activity in the Breast Cancer Therapy DOI
Edson D. Hernández‐Velázquez, Angélica Judith Granados‐López,

Jorge Gustavo Araujo-Huitrado

et al.

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(13)

Published: April 1, 2025

Abstract Maleimide core is a broadly used chemical‐based scaffold for natural and new compounds synthesis. Several of them show anticancer multidrug resistance (MDR) reversal activity. A family twelve 3,4‐substituted N ‐benzyl ‐methyl maleimides were synthesized in two‐step sequence consisting bromination Suzuki cross‐coupling or bromination–thiolation. We able to obtain two groups maleimide derivatives which tested determining their cytotoxicity. Following our previous work, the biological activity these as MDR agents was with cancerous cell line MCF‐7 that has been exposed chronically etoposide achieve MDR. resistant (MCF‐7R), treated combination synthetized compounds. The results presented strong effects 20 , 21 22 23 24, 25 no cells, IC 50 values proliferation inhibition ranged from 1.8–30.8 µM. between shows increase most except compound 15 where it shown low reversion degree. These findings suggest this work can be tumorigenic cancer cells before after acquiring resistance. should evaluated considering an undesirable effect caused due increase.

Language: Английский

Citations

0
An effective treatment approach of liposomally encapsulated metformin in colon cancer DOI
Enis A. Cetin, Olcay Boyacıoğlu, Seda Örenay-Boyacıoğlu

et al.

Medical Oncology, Journal Year: 2024, Volume and Issue: 41(4)

Published: Feb. 28, 2024

Language: Английский

Citations

3
Synthesis andin vivoEvaluation of Fluorobenzyl Metformin Derivatives as Potential Drugs in The Diabetes Treatment DOI
Edson D. Hernández‐Velázquez, Mayra Denise Herrera, Clara Alba Betancourt

et al.

Asian Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 12(7)

Published: May 23, 2023

Abstract Metformin is a versatile, biocompatible, and cheap bis‐guanidine used as first response line in the type II diabetes treatment. Since its human trials (1956) several structural modifications were carried out to increase activity. However, with this augmented activity, biological compatibility diminishes, generating serious side effects, such lactic acidosis. Considering that cytochrome P450 oversees metformin metabolism weakness eliminate fluorinated metabolites; we envisioned synthesis of benzyl derivatives. In our hypothesis fluorine atoms can give, by inductive effect, higher acidity hydrogen benzylic nitrogen, increasing solubility. On other hand, would give resistance cP450 allowing molecule acting longer. Thus, family fourteen fluorobenzyl metformins synthesized characterized, then an vitro enzymatic assay α‐amylase was performed select five best performing compounds, vivo experiment streptozotocin‐induced CD1 mice using selected Blood glucose measured every day. After sacrifice, lipid profile, serum, liver γ‐glutamyl transferase (GGT) activity determined biocompatibility. Results showed two compounds ( 1 L M ) enhanced biocompatibility for blood glucose, lipids GGT regulation.

Language: Английский

Citations

8
Oral Active Carbon Quantum Dots for Diabetes DOI Creative Commons
Gamze Çamlık, Besa Bilakaya, Esra Küpeli Akkol

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(10), P. 1395 - 1395

Published: Oct. 19, 2024

Metformin (Met), an oral drug used to treat type II diabetes, is known control blood glucose levels. carbon quantum dots (MetCQDs) were prepared enhance the bioavailability and effectiveness of metformin. Several studies have shown that (CQDs) attractive properties like small particle size, high penetrability, low cytotoxicity, ease synthesis. CQDs are made from a source, namely, citric acid, heteroatom, such as nitrogen. The active molecule can be source or reported here.

Language: Английский

Citations

2
Ningalins, Pyrrole‐Bearing Metabolites Isolated from Didemnum spp. Synthesis and MDR‐Reversion Activity in Cancer Therapy DOI Open Access
Luis A. Segura‐Quezada, Edson D. Hernández‐Velázquez, Alma Rosa Corrales Escobosa

et al.

Chemistry & Biodiversity, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 28, 2023

Abstract Multi‐Drug Resistance (MDR) is one of the most frequent problems observed in course cancer chemotherapy. Cells under treatment, tend to develop survival mechanisms drug‐action thus generating drug‐resistance. One important mechanism get it over expression P‐gp glycoprotein, which acts as an efflux‐pump releasing drug outside cell. A strategy for a succesfull treatment consists co‐administration compound that against and another cell during Ningalins are pyrrole‐containing naturally occurring compounds isolated mainly from marine tunicate Didemnum spp also they some top reversing agents MDR acting on P‐gp. Considering relevance displayed these alkaloids or their core therapy, all total synthesis described date members ningalins family reviewed herein.

Language: Английский

Citations

4
Iodine(III) Reagents for the Aromatic Functionalization with Inorganic Groups DOI

Miriam P. Barrera-Nava,

Luis A. Segura‐Quezada, Jaime G. Ibarra‐Gutiérrez

et al.

Tetrahedron, Journal Year: 2024, Volume and Issue: 166, P. 134203 - 134203

Published: Aug. 28, 2024

Language: Английский

Citations

1
Mechanisms of NMDA Receptor Inhibition by Biguanide Compounds DOI Creative Commons

Arseniy S. Zhigulin,

Anastasiya O. Novikova,

Oleg I. Barygin

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(9), P. 1234 - 1234

Published: Sept. 19, 2024

N-methyl-D-aspartate (NMDA) receptors are inhibited by many medicinal drugs. The recent successful repurposing of NMDA receptor antagonists ketamine and dextromethorphan for the treatment major depressive disorder further enhanced interest in this field. In work, we performed a screening activity against native rat CA1 hippocampal pyramidal neurons among biguanide compounds using whole-cell patch-clamp method. Antimalarial biguanides proguanil cycloguanil, as well hypoglycemic phenformin, them micromolar concentrations, while another metformin antiviral moroxydine were practically ineffective. IC50 values at −80 mV holding voltage 3.4 ± 0.6 µM 9.0 2.2 13 1 phenformin. inhibition all three was not competitive. Cycloguanil acted an voltage-dependent trapping channel blocker, phenformin allosteric inhibitors. Our results support potential clinical neurodegenerative disorders linked to glutamatergic excitotoxicity also providing better understanding structural determinants antagonism biguanides.

Language: Английский

Citations

1