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1.
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.

2.
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.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39005117

RESUMO

Glucose monitoring is essential for managing diabetes, and continuous glucose monitoring biosensors can offer real-time monitoring with little invasiveness. However, challenges remain in improving sensor accuracy, selectivity, and overall performance. This article aims to review current trends and recent advancements in glucose-monitoring biosensors while evaluating their benefits and limitations for diabetes monitoring. An analysis of current literature on transdermal glucose sensors was conducted, focusing on detection techniques, novel nanomaterials, and integrated sensor systems. Recent research has led to advancements in electrochemical, optical, electromagnetic, and sonochemical sensors for transdermal glucose detection. The use of novel nanomaterials and integrated sensor designs has improved sensitivity, selectivity, and accuracy. However, issues like calibration requirements, motion artifacts, and skin irritation persist. Transdermal glucose sensors show promise for non-invasive, convenient diabetes monitoring but require further enhancements to address limitations in accuracy, reliability, and biocompatibility. Continued research and innovation focusing on sensor materials, designs, and surface chemistry is needed to optimize biosensor performance and utility. The study offers a comprehensive analysis of the present status of technological advancement and highlights areas that need more research.

4.
Indian J Tuberc ; 71 Suppl 1: S117-S129, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39067943

RESUMO

A large number of people annually lose their lives to tuberculosis (TB), which is an age-old disease caused by the Mycobacterium tuberculosis. The global spread of TB is a concern for all regions. The south-east Asian region recorded 46% of all new TB cases in 2021, followed by the African and western Pacific regions with 23% and 18%, respectively. Researchers are always searching at natural substances for potential alternative therapeutics to tackle the worrisome growth in multi-drug-resistant (MDR) tuberculosis due to the high costs associated with developing new treatments and unfavourable side effects of currently used synthetic pharmaceuticals. Phytochemicals show promising results as a future health aid due to their multi-targeting ability on pathogen cells. In the search for new drug leads, the Ayurvedic and Siddha medical systems have made an extensive use of ethnomedicinal tools, including the use of plants like Amalaki (Emblica officinalis Gaertn.), Guduchi (Tinospora cordifolia willd.), Sariva (Hemidesmus indicus R.Br.), Kustha (Saussurea lappa Falc.), turmeric (Curcuma longa Mal.) and Green tea (Camellia sinensis Linn.). These sources are high in flavonoids, polyphenols, tannins and catechins, has been shown to reduce the risk of TB. In this overview, we look at how natural sources like plants, algae and mushrooms have helped researchers to find new drug leads, and how to back these natural sources through mapping the molecular approaches and other approaches has helped them to defeat MDR.


Assuntos
Antituberculosos , Descoberta de Drogas , Compostos Fitoquímicos , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Ayurveda , Fitoterapia
5.
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
6.
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.

7.
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.

8.
Chem Biodivers ; : e202400642, 2024 Jun 01.
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.

9.
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.

10.
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
11.
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.

12.
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
13.
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
14.
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
15.
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
16.
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
17.
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
18.
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
19.
Artigo em Inglês | MEDLINE | ID: mdl-38047361

RESUMO

BACKGROUND: Type 2 diabetes mellitus constitutes approximately 90% of all reported forms of diabetes mellitus. Insulin resistance characterizes this manifestation of diabetes. The prevalence of this condition is commonly observed in patients aged 45 and above; however, there is an emerging pattern of younger cohorts receiving diagnoses primarily attributed to lifestyle-related variables, including obesity, sedentary behavior, and poor dietary choices. The enzyme SGLT2 exerts a negative regulatory effect on insulin signaling pathways, resulting in the development of insulin resistance and subsequent elevation of blood glucose levels. The maintenance of glucose homeostasis relies on the proper functioning of insulin signaling pathways, while disruptions in insulin signaling can contribute to the development of type 2 diabetes. OBJECTIVE: Our study aimed to investigate the role of SGLT2. This enzyme interferes with insulin signaling pathways and identifies potential SGLT2 inhibitors as a treatment for managing type 2 diabetes. METHODS: We screened the Maybridge HitDiscover database to identify potent hits followed by druglikeness, Synthetic Accessibility, PAINS alert, toxicity estimation, ADME assessment, and Consensus Molecular docking. RESULTS: The screening process led to the identification of three molecules that demonstrated significant binding affinity, favorable drug-like properties, effective ADME, and minimal toxicity. CONCLUSION: The identified molecules could manage T2DM effectively by inhibiting SGLT2, providing a promising avenue for future therapeutic strategies.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38031767

RESUMO

BACKGROUND: Considering the limited number of current effective treatments, Multidrug- Resistant (MDR) illnesses have grown to be a serious concern to public health. It has become necessary to look for new antimicrobial drugs because of the emergence of resistance to numerous kinds of antibiotics. The use of flavonoids is one phytotherapeutic strategy that has been researched as a potential remedy for this issue. Secondary plant compounds called flavonoids have been found to have an antibacterial effect against resistant microorganisms. OBJECTIVE: This review seeks to give readers a glimpse into contemporary studies on flavonoids' potential to fight MDR infections. METHODS: A systematic search was conducted on electronic databases (PubMed, Scopus, and Google Scholar) using relevant keywords such as flavonoids, MDR infections, antimicrobial activity, and resistance microbes. Studies that investigated the antimicrobial activity of flavonoids against resistant microbes were included in this review. RESULTS: Most research found that flavonoids have antibacterial efficacy against resistant microorganisms, and some also showed that they have synergistic benefits with traditional antibiotics. The flavonoids quercetin, kaempferol, apigenin, and luteolin were the most often investigated ones. According to research, flavonoids affect microbial gene expression, inhibit microbial enzymes, and disrupt the integrity of microbial cell membranes. Additionally, a few studies have noted the flavonoids' low toxicity and safety. CONCLUSION: For the treatment of infections that are resistant to many drugs, flavonoids constitute a promising class of phytotherapeutic agents. To develop flavonoid-based treatment methods for treating MDR illnesses and assess the potential of flavonoids as adjuvants to conventional antimicrobial drugs, more study is required.

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