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1.
Chem Biodivers ; 21(8): e202400642, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38822644

RESUMO

New 2-(4-benzothiazol-2-yl-phenoxy)-1-(3,5-diphenyl-4,5-dihydro-pyrazol-1-yl)-ethanones (9a-o) have been designed and synthesized. All the synthesized compounds were characterized by thin layer chromatography and spectral analysis. The antiepileptic potential of the synthesized compounds has been tested by following standard animal screening models, including maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) models. The neurotoxic and antidepression effects of the synthesized compounds were checked by utilizing rotarod apparatus, and motor impairment test (by actophotometer) respectively. The study concluded that compounds 9c, 9d, 9f, 9i, 9n, and 9o possessed good antiepileptic potential compared to standard drugs like carbamazepine and phenytoin. The results of the rotarod performance test also established them without any neurotoxicity. The motor impairment test revealed that the synthesized compounds are also good antidepressants. In-silico studies have been performed for calculation of pharmacophore pattern, prediction of pharmacokinetic properties which determine the eligibility of synthesized compounds as orally administered molecules and interactions with the target proteins. The result of in-silico studies reinforced results obtained by in vivo study of the synthesized compounds and their possible mechanism of antiepileptic action i. e. via inhibiting voltage-gated sodium channels (VGSCs) and gamma-aminobutyric acid-A receptor.


Assuntos
Anticonvulsivantes , Benzotiazóis , Pirazóis , Anticonvulsivantes/química , Anticonvulsivantes/síntese química , Anticonvulsivantes/farmacologia , Animais , Benzotiazóis/química , Benzotiazóis/antagonistas & inibidores , Benzotiazóis/farmacologia , Benzotiazóis/síntese química , Camundongos , Pirazóis/química , Pirazóis/farmacologia , Pirazóis/síntese química , Pentilenotetrazol , Eletrochoque , Relação Estrutura-Atividade , Convulsões/tratamento farmacológico , Convulsões/induzido quimicamente , Masculino , Estrutura Molecular , Simulação de Acoplamento Molecular , Modelos Animais de Doenças
2.
J Asian Nat Prod Res ; 26(6): 663-680, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38373215

RESUMO

Kinase is an enzyme that helps in the phosphorylation of the targeted molecules and can affect their ability to react with other molecules. So, kinase influences metabolic reactions like cell signaling, secretory processes, transport of molecules, etc. The increased activity of certain kinases may cause various types of cancer, i.e. leukemia, glioblastoma, and neuroblastomas. So, the growth of particular cancer cells can be prevented by the inhibition of the kinase responsible for those cancers. Natural products are the key resources for the development of new drugs where approximately 60% of anti-tumor drugs are being developed with the same including specific kinase dwellers. This study comprised molecular interactions of various molecules (obtained from natural sources) as kinase inhibitors for the treatment of cancer. It is expected that by analyzing the skeleton behavior, the process of action, and the body-related activity of these organic products, new cancer-avoiding molecules can be developed.


Assuntos
Antineoplásicos , Produtos Biológicos , Neoplasias , Inibidores de Proteínas Quinases , Humanos , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Estrutura Molecular , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/química
3.
J Assoc Physicians India ; 67(11): 32-36, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31793266

RESUMO

INTRODUCTION: Neuropathy is a comorbid complication of diabetes and Pregabalin and Duloxetine are the two most common drugs used for the treatment of neuropathic pain. AIM: To determine the effectiveness and side effects of Pregabalin and Duloxetine in patients with diabetic peripheral neuropathic pain. MATERIALS AND METHODS: This prospective observational study was conducted at Max Super Speciality Hospital. Patients attending the endocrinology department, above 18 years of age who were prescribed with Pregabalin or Duloxetine were screened and included in this study. The data was collected for all study participants using a specially designed case record form by conducting personal interviews. SF-MPQ, Mc-Gill, NRS and DN-4 questionnaires were used to assess the extent of pain and the side-effects associated with the drugs. RESULTS: Based on the responses from the Numerical Rating Scale and McGill Pain Questionnaire, Pregabalin was seen to be less effective compared to Duloxetine. The only side effect observed with Pregabalin was drowsiness, which was observed in 4% cases at 50 mg dose whereas those reported with Duloxetine were drowsiness (22.2% at 20 mg and 33.3% at 30 mg), vomiting (11.1% at 20mg and 30mg), headache (11.1% at 20 mg and 30 mg), and dizziness (0% at 20mg and 11.1% at 30 mg). CONCLUSION: Pregabalin has a better safety profile and tolerability compared to Duloxetine but the latter is more effective in treating Diabetic Peripheral Neuropathic Pain. However, further studies with a larger sample size and longer duration are required to be conducted for finding the effectiveness of these drugs, specifically in the Indian population.


Assuntos
Analgésicos , Neuropatias Diabéticas , Cloridrato de Duloxetina , Neuralgia , Pregabalina , Adulto , Analgésicos/uso terapêutico , Neuropatias Diabéticas/tratamento farmacológico , Cloridrato de Duloxetina/uso terapêutico , Humanos , Pregabalina/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento
5.
BMC Complement Altern Med ; 15: 270, 2015 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-26264241

RESUMO

BACKGROUND: The incidents of drug resistant microorganisms and the need of treatments for newly emerging pathogens are of great concern to the global community. Our ability to treat infectious diseases is dependent on the development of new pharmaceuticals, and one potential source being medicinal plants with traditional claims. The leaves of Aloe trigonantha L.C. Leach, an endemic Ethiopian plant, are locally used for the treatment of infectious and inflammatory diseases. This study explores the potential of the latex of this plant and compounds isolated thereof for their in vitro antibacterial and antifungal properties. METHODS: Analytical RP-HPLC and silica gel preparative TLC were used for identification and isolation of active constituents, respectively. Characterization of the compounds was based on UV, IR, HR-ESIMS, (1)H and (13)C NMR, and 2D-NMR spectral assignments. Antimicrobial activity studies were carried out against 21 pathogenic bacterial and 4 fungal strains using the disk diffusion method. Minimum inhibitory concentrations (MICs) were determined by the broth dilution method. RESULTS: A C-glycosylated chromone identified as aloesin, and three C-glycosylated anthrones characterized as 8-O-methy-7-hydroxyaloin A/B, aloin A/B and aloin-6'-O-acetate A/B were isolated. The latex and isolated compounds exhibited in vitro antibacterial activity against the tested pathogens. In some cases the activity of the isolated compounds (MIC = 10 µg/mL) was comparable with that of the standard drug ciprofloxacin, particularly against some of the Gram-negative bacterial strains tested. However, their activity towards the fungal pathogens tested was relatively weaker showing maximum activity against Candida albicans with MIC value of 400 µg/mL. CONCLUSION: The present findings can be used for further research aimed at the development of new antibacterial agents, and may also justify the ethnomedicinal claim of the plant for the treatment of infectious diseases.


Assuntos
Aloe/química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Látex/química , Látex/farmacologia , Candida albicans/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Folhas de Planta/química
6.
BMC Complement Altern Med ; 15: 282, 2015 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-26283230

RESUMO

BACKGROUND: The traditional use of the oleo-gum-resin of Commiphora guidottii Chiov. ex. Guid., which is commonly called scented myrrh, for topical treatment of wound is well documented. The major objective of the present study was to investigate the essential oil and resin obtained from C. guidottii for their potential wound healing properties. Due to their influence on the wound healing process, the anti-inflammatory and antimicrobial activities of scented myrrh have also been investigated. METHODS: Powdered oleo-gum-resin of C. guidottii was steam-distilled to obtain essential oil, and the resin was extracted from the marc with MeOH and filtered. The TLC fingerprint profile of the resin has been recorded by using silica gel GF254 as stationary phase. The essential oil components were identified and quantified by GC-MS. Ointments prepared from the essential oil (4% v/w) and the resin (5% w/w) were used for wound healing activity tests. Toxicity of the formulated ointments was investigated according to Draize skin irritation test. Acute anti-inflammatory effect in mice was evaluated using carrageenan induced mouse hind paw oedema model. Antimicrobial activity tests were carried out using disk diffusion and broth dilution techniques against 21 pathogenic bacterial and 4 fungal strains. RESULTS: Ointment formulations of both the oil and resin were found to be non-irritant at the concentrations used and showed significant (p<0.05-0.001) increase in wound contraction rate, shorter epithelization time and higher skin breaking strength as compared to the negative control. Overall, the antibacterial and antifungal activities of the oil and resin were comparable with the standard antibiotics ciprofloxacin and griseofulvin, respectively. CONCLUSION: The results confirm that scented myrrh possesses genuine wound healing activity supporting the traditional use of the plant.


Assuntos
Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Commiphora/química , Fitoterapia , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Ferimentos Penetrantes/tratamento farmacológico , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Carragenina , Edema/induzido quimicamente , Edema/tratamento farmacológico , Feminino , Masculino , Camundongos , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Pomadas , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Gomas Vegetais , Resinas Vegetais , Testes de Irritação da Pele , Resistência à Tração , Terpenos/farmacologia , Terpenos/uso terapêutico
7.
Cent Nerv Syst Agents Med Chem ; 24(1): 45-56, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38305393

RESUMO

Alzheimer's disease (AD) is an onset and incurable neurodegenerative disorder that has been linked to various genetic, environmental, and lifestyle factors. Recent research has revealed several potential targets for drug development, such as the prevention of Aß production and removal, prevention of tau hyperphosphorylation, and keeping neurons alive. Drugs that target numerous ADrelated variables have been developed, and early results are encouraging. This review provides a concise map of the different receptor signaling pathways associated with Alzheimer's Disease, as well as insight into drug design based on these pathways. It discusses the molecular mechanisms of AD pathogenesis, such as oxidative stress, aging, Aß turnover, thiol groups, and mitochondrial activities, and their role in the disease. It also reviews the potential drug targets, in vivo active agents, and docking studies done in AD and provides prospects for future drug development. This review intends to provide more clarity on the molecular processes that occur in Alzheimer's patient's brains, which can be of use in diagnosing and preventing the condition.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Humanos , Animais , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/antagonistas & inibidores , Terapia de Alvo Molecular/métodos , Proteínas tau/metabolismo , Proteínas tau/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
8.
Daru ; 32(1): 379-419, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38225520

RESUMO

PURPOSE: Chronic diseases often hinder the natural healing process, making wound infections a prevalent clinical concern. In severe cases, complications can arise, potentially leading to fatal outcomes. While allopathic treatments offer numerous options for wound repair and management, the enduring popularity of herbal medications may be attributed to their perceived minimal side effects. Hence, this review aims to investigate the potential of herbal remedies in efficiently treating wounds, presenting a promising alternative for consideration. METHODS: A literature search was done including research, reviews, systematic literature review, meta-analysis, and clinical trials considered. Search engines such as Pubmed, Google Scholar, and Scopus were used while retrieving data. Keywords like Wound healing 'Wound healing and herbal combinations', 'Herbal wound dressing', Nanotechnology and Wound dressing were used. RESULT: This review provides valuable insights into the role of natural products and technology-based formulations in the treatment of wound infections. It evaluates the use of herbal remedies as an effective approach. Various active principles from herbs, categorized as flavonoids, glycosides, saponins, and phenolic compounds, have shown effectiveness in promoting wound closure. A multitude of herbal remedies have demonstrated significant efficacy in wound management, offering an additional avenue for care. The review encompasses a total of 72 studies, involving 127 distinct herbs (excluding any common herbs shared between studies), primarily belonging to the families Asteraceae, Fabaceae, and Apiaceae. In research, rat models were predominantly utilized to assess wound healing activities. Furthermore, advancements in herbal-based formulations using nanotechnology-based wound dressing materials, such as nanofibers, nanoemulsions, nanofiber mats, polymeric fibers, and hydrogel-based microneedles, are underway. These innovations aim to enhance targeted drug delivery and expedite recovery. Several clinical-based experimental studies have already been documented, evaluating the efficacy of various natural products for wound care and management. This signifies a promising direction in the field of wound treatment. CONCLUSION: In recent years, scientists have increasingly utilized evidence-based medicine and advanced scientific techniques to validate the efficacy of herbal medicines and delve into the underlying mechanisms of their actions. However, there remains a critical need for further research to thoroughly understand how isolated chemicals extracted from herbs contribute to the healing process of intricate wounds, which may have life-threatening consequences. This ongoing research endeavor holds great promise in not only advancing our understanding but also in the development of innovative formulations that expedite the recovery process.


Assuntos
Plantas Medicinais , Cicatrização , Cicatrização/efeitos dos fármacos , Humanos , Plantas Medicinais/química , Animais , Fitoterapia , Bandagens , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico
9.
Artigo em Inglês | MEDLINE | ID: mdl-39021169

RESUMO

In the current scenario, obesity is a stimulating health problem and is growing very rapidly in the world. It is a complex disease caused by the imbalance between the energy intake and the energy expenditure. There are various diseases associated with obesity, i.e., diabetes, hypertension, cancer, atherosclerosis, and other cardiovascular problems, which produce a serious impact on the social and financial system of the population. Moreover, changing the lifestyle and other behavioral changes might help in decreasing weight loss, but it is quite challenging to achieve. Nearly 10-20% of males and 20-30% of females come under the obese condition. The most convenient therapy for treating obesity is the use of synthetic drugs available in the markets, like orlistat and sibutramine, but these drugs have serious side effects, along with this surgical procedure, and are also not safe. Various herbal medicines and bioactives are preferred as game changers. Many herbal plants and their bioactive compounds have recently demonstrated promising effects in treating obesity. They achieve this by acting on various signaling pathways, reducing the levels of hormones associated with obesity, and regulating the abundance and composition of gut microbiota. This review concludes by highlighting the potential role of various herbal plants in managing obesity.

10.
Chem Biol Drug Des ; 103(1): e14384, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37919259

RESUMO

Breast cancer is a common and deadly disease, so there is a constant need for research to find efficient targets and therapeutic approaches. Breast cancer can be classified on a molecular and histological base. Breast cancer can be divided into ER (estrogen receptor)-positive and ER-negative, HER2 (human epidermal growth factor receptor2)-positive and HER2-negative subtypes based on the presence of specific biomarkers. Targeting hormone receptors, such as the HER2, progesterone receptor (PR), and ER, is very significant and plays a vital role in the onset and progression of breast cancer. Endocrine treatments and HER2-targeted drugs are examples of targeted therapies now being used against these receptors. Emerging immune-based medicines with promising outcomes in the treatment of breast cancer include immune checkpoint inhibitors, cancer vaccines, and adoptive T-cell therapy. It is also explored how immune cells and the tumor microenvironment affect breast cancer development and treatment response. The major biochemical pathways, signaling cascades, and DNA repair mechanisms that are involved in the development and progression of breast cancer, include the PI3K/AKT/mTOR system, the MAPK pathway, and others. These pathways are intended to be inhibited by a variety of targeted drugs, which are then delivered with the goal of restoring normal cellular function. This review aims to shed light on types of breast cancer with the summarization of different therapeutic approaches which can target different pathways for tailored medicines and better patient outcomes.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Receptores de Estrogênio/metabolismo , Transdução de Sinais , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Receptores de Progesterona/uso terapêutico , Receptor ErbB-2/metabolismo , Microambiente Tumoral
11.
Recent Pat Anticancer Drug Discov ; 19(3): 257-267, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37497702

RESUMO

Among the deadliest diseases, cancer is characterized by tumors or an increased number of a specific type of cell because of uncontrolled divisions during mitosis. Researchers in the current era concentrated on the development of highly selective anticancer medications due to the substantial toxicities of conventional cytotoxic drugs. Several marketed drug molecules have provided resistance against cancer through interaction with certain targets/growth factors/enzymes, such as Telomerase, Histone Deacetylase (HDAC), Methionine Aminopeptidase (MetAP II), Thymidylate Synthase (TS), Glycogen Synthase Kinase-3 (GSK), Epidermal Growth Factor (EGF), Vascular Endothelial Growth Factor (VEGF), Focal Adhesion Kinase (FAK), STAT3, Thymidine phosphorylase, and Alkaline phosphatase. The molecular structure of these drug molecules contains various heterocyclic moieties that act as pharmacophores. Recently, 1,3,4- oxadiazole (five-membered heterocyclic moiety) and its derivatives attracted researchers as these have been reported with a wide range of pharmacological activities, including anti-cancer. 1,3,4- oxadiazoles have exhibited anti-cancer potential via acting on any of the above targets. The presented study highlights the synthesis of anti-cancer 1,3,4-oxadiazoles, their mechanism of interactions with targets, along with structure-activity relationship concerning anti-cancer potential.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Oxidiazóis/farmacologia , Oxidiazóis/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Estrutura Molecular , Relação Estrutura-Atividade , Neoplasias/tratamento farmacológico
12.
Artigo em Inglês | MEDLINE | ID: mdl-38879771

RESUMO

Mild Cognitive Impairment (MCI) is swiftly emerging as a prevalent clinical concern within the elderly demographic. Willoughby spearheaded the pioneering investigation into the evolution of memory decline spanning from the age of 20 to 70. Employing a computerized substitution examination, he pinpointed a zenith in memory prowess at the age of 22, signifying the shift from infancy, succeeded by a gradual decline in later years in 1929. Cognitive impairment impacts various facets, encompassing cognition, memory, perceptual acuity, and linguistic proficiency. Compelling evidence indicates that genetic, dietary, and metabolic factors influence the trajectory of cognitive decline in this patient cohort. In addition to the widely recognized influence of the Mediterranean diet on cognitive function, numerous studies have delved into the potential impact of diverse phytochemicals on cognitive deterioration. Many of these compounds are renowned for their inflammation reducer or free-radical scavenger properties, coupled with their commendable acceptability and defense profiles. Phytochemicals sourced from medicinal plants play an essential role in upholding the intricate chemical equilibrium of the brain by modulating receptors linked to crucial inhibitory neurotransmitters. Across the annals of historical medicinal traditions, a multitude of plants have been cataloged for their efficacy in mitigating cognitive disorders. This study presents a concise examination of distinct medicinal herbs, highlighting their neuroprotective phytochemical components such as fatty acids, phenols, alkaloids, flavonoids, saponins, terpenes, and beyond. The principal objective of this inquiry is to meticulously inspect and provide discernment into the extant evidence concerning phytochemicals exhibiting clinically demonstrable effects on cognitive decline.

13.
Med Chem ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38918990

RESUMO

The most common heterocyclic aromatic molecule with potential uses in industry and medicine is quinoline. Its chemical formula is C9H7N, and it has a distinctive double-ring structure with a pyridine moiety fused with a benzene ring. Various synthetic approaches synthesize quinoline derivatives. These approaches include solvent-free synthetic approach, mechanochemistry, ultrasonic, photolytic synthetic approach, and microwave and catalytic synthetic approaches. One of the important synthetic approaches is a catalyst-based synthetic approach in which different catalysts are used such as silver-based catalysts, titanium-based nanoparticle catalysts, new iridium catalysts, barium-based catalysts, iron-based catalysts, gold-based catalysts, nickel-based catalyst, some metal-based photocatalyst, α-amylase biocatalyst, by using multifunctional metal-organic framework-metal nanoparticle tandem catalyst etc. In the present study, we summarized different catalyst-promoted reactions that have been reported for the synthesis of quinoline. Hopefully, the study will be helpful for the researchers.

14.
Med Chem ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38685782

RESUMO

The versatile basic structure of piperazine allows for the development and production of newer bioactive molecules that can be used to treat a wide range of diseases. Piperazine derivatives are unique and can easily be modified for the desired pharmacological activity. The two opposing nitrogen atoms in a six-membered piperazine ring offer a large polar surface area, relative structural rigidity, and more acceptors and donors of hydrogen bonds. These properties frequently result in greater water solubility, oral bioavailability, and ADME characteristics, as well as improved target affinity and specificity. Various synthetic protocols have been reported for piperazine and its derivatives. In this review, we focused on recently published synthetic protocols for the synthesis of the piperazine and its derivatives. The structure-activity relationship concerning different biological activities of various piperazine-containing drugs was also highlighted to provide a good understanding to researchers for future research on piperazines.

15.
Chem Biol Drug Des ; 103(3): e14498, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38453241

RESUMO

The research involves the synthesis of a series of new pyridine analogs 5(i-x) and their evaluation for anti-epileptic potential using in silico and in vivo models. Synthesis of the compounds was accomplished by using the Vilsmeier-Haack reaction principle. AutoDock 4.2 was used for their in silico screening against AMPA (-amino-3-hydroxy-5-methylisoxazole) receptor (PDB ID:3m3f). For in vivo testing, the maximal electroshock seizure (MES) model was used. The physicochemical, pharmacokinetic, drug-like, and drug-score features of all synthesized compounds were assessed using the online Swiss ADME and Protein Plus software. The in silico results showed that all the synthesized compounds 5(i-x) had 1-3 interactions and affinities ranging from -6.5 to -8.0 kJ/mol with the targeted receptor compared to the binding affinities of the standard drug phenytoin and the original ligand of the target (P99), which were -7.6 and -6.8 kJ/mol, respectively. In vivo study results showed that the compound 5-Carbamoyl-2-formyl-1-[2-(4-nitrophenyl)-2-oxo-ethyl]-pyridinium gave 60% protection against epileptic seizures compared to 59% protection afforded by regular phenytoin. All of them met Lipinski's rule of five and had drug-likeness and drug score values of 0.55 and 0.8, respectively, making them chemically and functionally like phenytoin. According to the findings of the studies, the synthesized derivatives have the potential to be employed as a stepping stone in the development of novel anti-epileptic drugs.


Assuntos
Anticonvulsivantes , Fenitoína , Humanos , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/uso terapêutico , Fenitoína/uso terapêutico , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Convulsões/tratamento farmacológico , Convulsões/prevenção & controle , Piridinas/uso terapêutico
16.
Cell Biochem Biophys ; 82(1): 15-34, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38048024

RESUMO

Cystic fibrosis is a genetic disorder inherited in an autosomal recessive manner. It is caused by a mutation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene on chromosome 7, which leads to abnormal regulation of chloride and bicarbonate ions in cells that line organs like the lungs and pancreas. The CFTR protein plays a crucial role in regulating chloride ion flow, and its absence or malfunction causes the production of thick mucus that affects several organs. There are more than 2000 identified mutations that are classified into seven categories based on their dysfunction mechanisms. In this article, we have conducted a thorough examination and consolidation of the diverse array of tests essential for the quantification of CFTR functionality. Furthermore, we have engaged in a comprehensive discourse regarding the recent advancements in CFTR modulator therapy, a pivotal approach utilized for the management of cystic fibrosis, alongside its concomitant relevance in evaluating CFTR functionality.


Assuntos
Fibrose Cística , Humanos , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Cloretos/metabolismo , Mutação , Transdução de Sinais
17.
Curr Drug Targets ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38879770

RESUMO

Arthritis, a prevalent inflammatory joint condition, presents challenges for effective therapeutic interventions, with conventional treatments often limited in efficacy and associated with adverse effects. Recent years have witnessed a growing interest in exploring natural compounds, particularly phytoconstituents, renowned for their anti-inflammatory and joint-protective properties. This review aims to illuminate the potential of employing nanotherapeutic approaches with phytoconstituents for enhanced arthritis management. The integration of nanotechnology with phytoconstituents emerges as a promising strategy, addressing limitations in traditional arthritis treatments. Nanocarriers like liposomes and nanoparticles provide a platform for targeted drug delivery, improving the bioavailability of phytoconstituents. Furthermore, the combined effects of phytoconstituents can be leveraged to target multiple pathways in arthritis pathogenesis, including inflammation, oxidative stress, and cartilage degradation. Key phytoconstituents, such as curcumin, resveratrol, and quercetin, exhibit anti-inflammatory and immunomodulatory properties. Nevertheless, their therapeutic potential is often impeded by challenges like poor solubility, stability, and bioavailability. Nanocarriers offer solutions by enhancing pharmacokinetics and enabling sustained release, thereby boosting overall therapeutic efficacy. The review explores the mechanisms underlying the anti-arthritic effects of phytoconstituents and their nanoformulations, including the modulation of pro-inflammatory cytokines, inhibition of matrix metalloproteinases, and reduction of oxidative stress. In summary, the integration of phytoconstituents with nanotechnology presents a promising avenue for developing targeted and effective arthritis therapies. This comprehensive review serves as a valuable resource for researchers, clinicians, and pharmaceutical developers seeking innovative approaches to address the intricate challenges associated with arthritis management.

18.
Chem Biol Drug Des ; 103(6): e14537, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38888058

RESUMO

The versatile basic structure of piperazine allows for the development and production of newer bioactive molecules that can be used to treat a wide range of diseases. Piperazine derivatives are unique and can easily be modified for the desired pharmacological activity. The two opposing nitrogen atoms in a six-membered piperazine ring offer a large polar surface area, relative structural rigidity, and more acceptors and donors of hydrogen bonds. These properties frequently result in greater water solubility, oral bioavailability, and ADME characteristics, as well as improved target affinity and specificity. Various synthetic protocols have been reported for piperazine and its derivatives. In this review, we focused on recently published synthetic protocols for the synthesis of the piperazine and its derivatives. The structure-activity relationship concerning different biological activities of various piperazine-containing drugs has also been highlighted to provide a good understanding to researchers for future research on piperazines.


Assuntos
Química Farmacêutica , Piperazinas , Piperazinas/química , Piperazinas/síntese química , Humanos , Relação Estrutura-Atividade , Animais
19.
Chem Biol Drug Des ; 103(6): e14552, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38825735

RESUMO

The five-membered 1,3,4-oxadiazole heterocyclic ring has received considerable attention because of its unique bio-isosteric properties and an unusually wide spectrum of biological activities. After a century since 1,3,4-oxadiazole was discovered, its uncommon potential attracted medicinal chemist's attention, leading to the discovery of a few presently accessible drugs containing 1,3,4-oxadiazole units, and a large number of patents have been granted on research related to 1,3,4-oxadiazole. It is worth noting that interest in 1,3,4-oxadiazoles' biological applications has doubled in the last few years. Herein, this review presents a comprehensive overview of the recent achievements in the synthesis of 1,3,4-oxadiazole-based compounds and highlights the major advances in their biological applications in the last 10 years, as well as brief remarks on prospects for further development. We hope that researchers across the scientific streams will benefit from the presented review articles for designing their work related to 1,3,4-oxadiazoles.


Assuntos
Oxidiazóis , Oxidiazóis/química , Oxidiazóis/farmacologia , Humanos
20.
Curr Gene Ther ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39092652

RESUMO

MicroRNAs (miRNAs) have emerged as a significant tool in the realm of vaccinology, offering novel approaches to vaccine development. This study investigates the potential of miRNAs in the development of advanced vaccines, with an emphasis on how they regulate immune response and control viral replication. We go over the molecular features of miRNAs, such as their capacity to direct post-transcriptional regulation toward mRNAs, hence regulating the expression of genes in diverse tissues and cells. This property is harnessed to develop live attenuated vaccines that are tissue-specific, enhancing safety and immunogenicity. The review highlights recent advancements in using miRNA-targeted vaccines against viruses like influenza, poliovirus, and tick-borne encephalitis virus, demonstrating their attenuated replication in specific tissues while retaining immunogenicity. We also explored the function of miRNAs in the biology of cancer, highlighting their potential to develop cancer vaccines through targeting miRNAs that are overexpressed in tumor cells. The difficulties in developing miRNA vaccines are also covered in this work, including delivery, stability, off-target effects, and the requirement for individualized cancer treatment plans. We wrap off by discussing the potential of miRNA vaccines and highlighting how they will influence the development of vaccination techniques for cancer and infectious diseases in the future.

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