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1.
Artigo em Inglês | MEDLINE | ID: mdl-37904554

RESUMO

Myocardial infarction (MI), commonly known as a heart attack, is a critical cardiovascular condition associated with high morbidity and mortality rates worldwide. Despite significant advancements in traditional treatment modalities, there remains a need for innovative approaches to improve the prognosis and treatment outcomes of MI. The emergence of nanotechnology has provided a promising avenue for revolutionizing the management of this life-threatening condition. This manuscript aims to explore the role of nanotechnology in the prognosis and treatment of myocardial infarctions. Nanotechnology offers unique advantages in the field of cardiovascular medicine, including targeted drug delivery, precise imaging and diagnosis, regenerative medicine approaches, biosensors and monitoring, and the integration of therapy and diagnostics (theragnostic). One of the key advantages of nanotechnology is the ability to deliver therapeutic agents directly to the affected site. Nanoparticles can be engineered to carry drugs specifically to damaged heart tissue, enhancing their efficacy while minimizing off-target effects. Additionally, nanoparticles can serve as contrast agents, facilitating high-resolution imaging and accurate diagnosis of infarcted heart tissue. Furthermore, nanotechnology-based regenerative approaches show promise in promoting tissue healing and regeneration after MI. Nanomaterials can provide scaffolding structures or release growth factors to stimulate the growth of new blood vessels and support tissue repair. This regenerative potential holds significant implications for restoring cardiac function and minimizing long-term complications. Nanotechnology also enables real-time monitoring of critical parameters within the heart, such as oxygen levels, pH, and electrical activity, through the utilization of nanoscale devices and sensors. This capability allows for the early detection of complications and facilitates timely interventions. Moreover, the integration of therapy and diagnostics through nanotechnology-based platforms, known as theragnostic, holds tremendous potential. Nanoparticles can simultaneously deliver therapeutic agents while providing imaging capabilities, enabling personalized treatment strategies tailored to individual patients. This manuscript will review the recent advancements, clinical trials, and patents in nanotechnology for the prognosis and treatment of myocardial infarctions. By leveraging nanotechnology's unique properties and applications, researchers and clinicians can develop innovative therapeutic approaches that enhance patient outcomes, improve prognosis, and ultimately revolutionize the management of myocardial infarctions.

2.
Artigo em Inglês | MEDLINE | ID: mdl-37904559

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease, progressively distinctive via cartilage destruction, auto-antibody production, severe joint pain, and synovial inflammation. Nanotechnology represents as one of the utmost promising scientific technologies of the 21st century. It exhibits remarkable potential in the field of medicine, including imaging techniques and diagnostic tools, drug delivery systems and providing advances in treatment of several diseases with nanosized structures (less than 100nm). OBJECTIVE: Conventional drugs as a cornerstone of RA management including disease-modifying antirheumatic drugs (DMARDS), Glucocorticosteroids, etc are under clinical practice. Nevertheless, their low solubility profile, poor pharmacokinetics behaviour, and non-targeted distribution not only hamper their effectiveness, but also give rise to severe adverse effects which leads to the need for the emergence of nanoscale drug delivery systems. METHODS: Several types of nano-diagnostic agents and nanocarriers have been identified; including polymeric nanoparticles (NPs), liposomes, nanogels, metallic NPs, nanofibres, carbon nanotubes, nano fullerene etc. Various patents and clinical trial data have been reported in relevance to RA treatment. RESULTS: Nanocarriers, unlike standard medications, encapsulate molecules with high drug loading efficacy and avoid drug leakage and burst release before reaching the inflamed sites. Because of its enhanced targeting specificity with the ability to solubilise hydrophobic drugs, it acts as an enhanced drug delivery system. CONCLUSION: This study explores nanoparticles potential role in RA as a carrier for site-specific delivery and its promising strategies to overcome the drawbacks. Hence, it concludes that nanomedicine is advantageous compared with conventional therapy to enhanced futuristic approach.

3.
J Biochem Mol Toxicol ; 37(5): e23314, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36650745

RESUMO

The pesticide malathion (MT), an organophosphate, is highly neurotoxic and causes cholinergic disorders as well as cytotoxicity, genotoxicity, mutagenicity, carcinogenicity and reproductive toxicity. Our purpose was to study the effect of ellagic acid (EA) and Vitamin C on the testis against MT-induced toxicity in the rats. Thirty-six adult Wistar rats were employed, separated into six groups and were given treatment for 14 days. The toxicity of MT on the testis was evaluated using a variety of physical parameters, such as mortality rate and body weight, as well as biochemical parameters, such as total protein, total cholesterol, serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase, and haematological parameters, such as counts of red blood cells, haemoglobin (Hb) and white blood cells, as well as mean corpuscular volume, mean corpuscular Hb, and mean corpuscular Hb concentration. At the end of the experiment, rats were killed and a histological examination of the testis was performed. A sperm count technique and an analysis of sperm motility were used to determine the sperm quality. Biochemical indicators, sperm count, motility, viability and morphology were significantly decreased with MT. When compared with MT and the control group, EA and Vitamin C administration significantly increased sperm motility and count (p < 0.05). After receiving EA and Vitamin C, biochemical indicators and histological characteristics are also intensified. The results of the current investigation show that EA and Vitamin C can both reduce increased levels of biochemical markers and improve pathological alterations in the testis brought on by MT treatment.


Assuntos
Ácido Ascórbico , Testículo , Masculino , Ratos , Animais , Testículo/metabolismo , Ácido Ascórbico/farmacologia , Ratos Wistar , Malation/toxicidade , Antioxidantes/farmacologia , Ácido Elágico/farmacologia , Motilidade dos Espermatozoides , Sêmen/metabolismo
4.
Recent Pat Nanotechnol ; 17(4): 307-326, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35616680

RESUMO

BACKGROUND: Drugs with poor solubility exhibit hurdles in their formulation due to poor dissolution and low bioavailability. Nanocrystallization is a great technique for incorporating poorly soluble drugs and is associated with many benefits. OBJECTIVE: The objective of the present review is to discuss formulation techniques for the generation of Nanocrystals (NCs) and illustrate the various advantages of NCs. It also explains commonly used stabilizers and guidelines for their safe use for enhancing NCs and provides a deep insight into various biomedical applications of NCs. METHODS: The review was extracted from the study carried out in the general literature to emphasize the importance of NCs in various formulations. RESULTS: NCs are a widely accepted approach to enhancing drug solubility. There are so many marketed products of nanocrystal drug formulations that are being used to treat life-threatening disorders. Two techniques can be used to formulate NCs, i.e., the bottom-up method and the top-down method. Their main biomedical applications are found in oral, parenteral, pulmonary, ocular, dermal, and mucosal formulations. CONCLUSION: In the present review, different formulation methods of NCs have been discussed in detail, followed by explaining the advantages and various targeted drug delivery systems covered by NCs formulations. The development of NCs-based formulation avoids the limitations of other systems used for targeted drug delivery.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas , Preparações Farmacêuticas/química , Disponibilidade Biológica , Nanopartículas/química , Solubilidade
5.
Exp Brain Res ; 240(6): 1649-1659, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35488904

RESUMO

Wound healing is a highly coordinated and dynamic process of tissue repair after injury. The global burden of disease associated with wounds, both acute and chronic, is a significantly rising health concern. Upon skin wounding, neurons have the ability to sense the disruption to mediate the release of neurotransmitters into the wound microenvironment. Serotonin that has long been recognised as a potential vasoconstrictor is now also being contemplated to play a role in re-epithelialisation of wounds. While the role of neuropeptides in stimulating diabetic wound healing is being increasingly emphasised, on the other hand, dopamine is being widely studied for its dual role in mediating both pro- and antiangiogenic effects at the site of the wounds. Similarly, epinephrine levels that are known to be elevated during stress is now recognised as a contributing factor towards delayed wound closure, thereby serving as an inhibitor of wound healing. Thus, each neurotransmitter regulates wound repair and their active regeneration in a typical way. Strengthening our understanding of the molecular pathways via which the neurotransmitter modulates the immune system to control wound healing can yield potential therapeutic measures. Further investigations regarding the safety, efficacy, and cost-effectiveness of these processes are a prerequisite for their possible translation into clinical trials.


Assuntos
Neuropeptídeos , Pele , Humanos , Neuropeptídeos/metabolismo , Neurotransmissores/metabolismo , Cicatrização/fisiologia
6.
Comb Chem High Throughput Screen ; 21(3): 194-203, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29436997

RESUMO

BACKGROUND: Malaria is one of the most vital infectious diseases caused by protozoan parasites of the Plasmodium genus. As P. falciparum, the cause of most of the severe cases of malaria, is increasingly resistant to available drugs such as amodioquine, chloroquine, artemisinin, and antifolates, there is an urgent need to identify new targets for chemotherapy. OBJECTIVE: This study screened novel pyrazole derivatives carrying iminium & benzothiazole group for antimalarial potential against P. falciparum chloroquine sensitive (3D7) strain. MATERIALS & METHODS: Several pyrazole schiff base hybrids with a wide range of substitution have been synthesized via condensation of substituted aniline with substituted 4-formylpyrazole and evaluated for their in vitro antimalarial activity against asexual blood stages of human malaria parasite, Plasmodium falciparum. The interaction of these conjugate hybrids was also investigated by molecular docking studies in the binding site of P. falciparum cystein protease falcipain-2. The pharmacokinetic properties were also studied using ADME prediction. RESULTS: Among all compounds, 6bf and 6bd were found to be potential molecules with EC50 1.95µg/ml and 1.98µg/ml respectively. Docking study results reveal that the pyrazole schiff base derivatives occupy the PfFP binding sites and they show good interactions with significant values of binding energies. CONCLUSION: We provide evidence which implicates pyrazole Schiff base hybrids as potential prototypes for the development of antimalarial agents.


Assuntos
Antimaláricos/síntese química , Pirazóis/uso terapêutico , Bases de Schiff/uso terapêutico , Antimaláricos/metabolismo , Benzotiazóis/química , Biologia Computacional , Cisteína Endopeptidases/metabolismo , Avaliação Pré-Clínica de Medicamentos , Humanos , Iminas/química , Simulação de Acoplamento Molecular , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/enzimologia , Pirazóis/química , Bases de Schiff/química
7.
Eur J Med Chem ; 123: 718-726, 2016 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-27521588

RESUMO

Synthesis of fourteen analogues of bacillamide, a bioactive tryptamide alkaloid of marine origin, has been accomplished through a highly efficient convergent route. The present solvent-free protocol involves the formation of thiazole ring in the initial step followed by amide coupling between substituted ethyl 2-alkyl/aryl/heteroaryl/amino/aminoarylthiazole-4-carboxylates and tryptamine in presence of 2-hydroxy-4,6-dimethylpyrimidine, a solid phase catalyst to yield N-[2-(1H-indol-3-yl)ethyl]-2-alkyl/aryl/heteroaryl/amino/aminoarylthiazole-4-carboxamides as bacillamide analogues having structural variation at position-2 of thiazole ring. Bacillamide and its analogues were evaluated for their cytotoxic activity against three cancer cell lines (HCT-116, MDA-MD-231 and JURKAT cell lines) using colorimetric cell proliferation assay. Compounds 17a and 17b exhibited potent anti-cell proliferation activity with IC50 values in the range of ∼3.0 µM and ∼0.1-0.6 µM, respectively against these cell lines. Preliminary mechanism of action studies indicates that these compounds initiate caspase dependent apoptosis. Also, compounds 16d, 16f, 17a and 17d exhibited excellent anti-inflammatory activity comparable to well-known NSAID indomethacin and better to bacillamide, when evaluated using carrageenan induced rat hind paw oedema method.


Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Tiazóis/síntese química , Tiazóis/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Química Verde , Humanos , Ratos , Relação Estrutura-Atividade , Tiazóis/química
8.
Chin J Integr Med ; 2016 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-27465423

RESUMO

Benincasa cerifera (Savi.), belonging to Cucurbitaceae, is an annual creepy wine that posses highm edicinal value and istraditionally used as fruit and medicine throughout India. In Indian system of medicine, its fruit is used as nutritive, tonic, diuretic, aphrodisiac, styptic, vermifuge and in various diseases and disorders like asthma, bronchitis, insanity, epilepsy, dry cough, fever, urethrorrhea, syphilis, hyperdipsia and vitiated conditions of pitta, etc. Phytochemically the plant is found to contain lupeol, ß-sitosterol, cucurbitacin B, iso-vitexin, etc. It has been demonstrated to posses numerous pharmacological activities such as antiepileptic, hepatoprotective, antioxidant, analgesic, immunopotentiator and anxiolytic, etc. In the present review there is a detailed description of its botany, phytochemistry, ethno-botany and pharmacological activities.

9.
Cent Nerv Syst Agents Med Chem ; 16(2): 158-64, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26844957

RESUMO

BACKGROUND: Heterocyclic compounds are extensively dispersed in nature and are vital for life. Various investigational approaches towards Structural Activity Relationship that focus upon the exploration of optimized candidates have become vastly important. METHOD: Literature studies tell that for a series of compounds that are imperative in industrial and medicinal chemistry, thiophene acts as parent. Among various classes of heterocyclic compounds that have potential central nervous system activity, thiophene is the most important one. In the largely escalating chemical world of heterocyclic compounds showing potential pharmacological character, thiophene nucleus has been recognized as the budding entity. RESULT: Seventeen Papers were included in this review article to define the central nervous system potential of thiophene. This review article enlightens the rationalized use and scope of thiophene scaffold as novel central nervous system activity such as anticonvulsant, acetylcholinesterase inhibitor, cyclin-dependent kinase 5 (cdk5/p25) inhibitors, CNS depressant, capability to block norepinephrine, serotonin and dopamine reuptake by their respective transporters etc. CONCLUSION: The Finding of this review confirm the importance of thiophene scaffold as potential central nervous system agents. From this outcome, ideas for future molecular modifications leading to the novel derivatives with better constructive pharmacological potential may be derived.


Assuntos
Fármacos do Sistema Nervoso Central/química , Fármacos do Sistema Nervoso Central/uso terapêutico , Tiofenos/química , Tiofenos/uso terapêutico , Animais , Doenças do Sistema Nervoso Central/tratamento farmacológico , Humanos , Estudos Prospectivos
10.
Eur J Med Chem ; 101: 326-33, 2015 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-26160113

RESUMO

A series of novel 2,5-diarylpyrazolo[1,5-a]pyrimidin-7-amines were designed as COX-2 inhibitors by molecular docking studies and their synthesis was accomplished via an expeditious one-pot reaction. Structures of the compounds were established by NMR ((1)H-(13)C), IR spectroscopy and high resolution mass spectrometry. All the eleven compounds have been screened for their in vivo anti-inflammatory activity on rats by carrageenan-induced rat paw edema assay. Correlation studies of calculated moldock score and observed percentage inhibition have also been carried out which concluded that the synthesized 2,5-diarylpyrazolo[1,5-a]pyrimidin-7-amines act as potent anti-inflammatory agents up to the 4th hour of study.


Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Desenho de Fármacos , Edema/tratamento farmacológico , Simulação de Acoplamento Molecular , Pirazóis/síntese química , Pirazóis/farmacologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Carragenina , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Masculino , Estrutura Molecular , Pirazóis/química , Pirimidinas/química , Ratos , Ratos Wistar , Relação Estrutura-Atividade
11.
Bioorg Med Chem Lett ; 25(6): 1177-81, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25702850

RESUMO

Current Letter presents design, synthesis and biological evaluation of a novel series of pyrazolylthiazole carboxylates 1a-1p and corresponding acid derivatives 2a-2p. All 32 novel compounds were tested for their in vivo anti-inflammatory activity by carrageenan-induced rat paw edema method as well as for in vitro antimicrobial activity. All the tested compounds exhibited excellent AI activity profile. Three compounds 1p (R=Cl, R(1)=Cl), 2c (R=H, R(1)=F) and 2n (R=Cl, R(1)=OCH3) were identified as potent anti-inflammatory agents exhibiting edema inhibition of 93.06-89.59% which is comparable to the reference drug indomethacin (91.32%) after 3h of carrageenan injection while most of the other compounds displayed inhibition ⩾80%. In addition, pyrazolylthiazole carboxylic acids (2a-2p) also showed good antimicrobial profile. Compound 2h (R=OCH3, R(1)=Cl) showed excellent antimicrobial activity (MIC 6.25µg/mL) against both Gram positive bacteria comparable with the reference drug ciprofloxacin (MIC 6.25µg/mL).


Assuntos
Anti-Infecciosos/síntese química , Anti-Inflamatórios/síntese química , Ácidos Carboxílicos/química , Animais , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ácidos Carboxílicos/farmacologia , Ácidos Carboxílicos/uso terapêutico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Fungos/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Indometacina/farmacologia , Indometacina/uso terapêutico , Testes de Sensibilidade Microbiana , Pirazóis/química , Ratos , Tiazóis/química
12.
Eur J Med Chem ; 85: 147-78, 2014 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-25084143

RESUMO

Malaria has emerged as a major health problem worldwide after the appearance of resistant strains of Plasmodium falciparum to the most of antimalarial drugs. The development of resistance by the parasite against first line as well as second line antimalarial drugs has drawn attention to develop new drugs to alleviate the disease burden. Therefore, there is a great need for new antimalarial drugs with improved attributes over older therapies. This review is primarily addressed to description of the recent advances in the synthesis of heterocyclic compound as antimalarial agents which can facilitate the development of more potent and effective antimalarial agents.


Assuntos
Antimaláricos/síntese química , Técnicas de Química Sintética/métodos , Antimaláricos/química , Compostos Heterocíclicos/química , Humanos
13.
Adv Bioinformatics ; 2014: 903246, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25114678

RESUMO

The present study attempts to establish a relationship between ethnopharmacological claims and bioactive constituents present in Pinus roxburghii against all possible targets for diabetes through molecular docking and to develop a pharmacophore model for the active target. The process of molecular docking involves study of different bonding modes of one ligand with active cavities of target receptors protein tyrosine phosphatase 1-beta (PTP-1ß), dipeptidyl peptidase-IV (DPP-IV), aldose reductase (AR), and insulin receptor (IR) with help of docking software Molegro virtual docker (MVD). From the results of docking score values on different receptors for antidiabetic activity, it is observed that constituents, namely, secoisoresinol, pinoresinol, and cedeodarin, showed the best docking results on almost all the receptors, while the most significant results were observed on AR. Then, LigandScout was applied to develop a pharmacophore model for active target. LigandScout revealed that 2 hydrogen bond donors pointing towards Tyr 48 and His 110 are a major requirement of the pharmacophore generated. In our molecular docking studies, the active constituent, secoisoresinol, has also shown hydrogen bonding with His 110 residue which is a part of the pharmacophore. The docking results have given better insights into the development of better aldose reductase inhibitor so as to treat diabetes related secondary complications.

14.
J Enzyme Inhib Med Chem ; 29(4): 476-84, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23777557

RESUMO

Synthesis of total eighteen 2-amino-substituted 4-coumarinylthiazoles including sixteen new compounds (3a-o and 5b) bearing the benzenesulfonamide moiety is described in the present report. All the synthesized target compounds were examined for their in vivo anti-inflammatory (AI) activity and in vitro antimicrobial activity. Results revealed that six compounds (3 d, 3 f, 3 g, 3 h, 3 j and 3 n) exhibited pronounced anti-inflammatory activity comparable to the standard drug indomethacin. AI results were further confirmed by the docking studies of the most active (3n) and the least active compound (3a) with COX-1 and COX-2 active sites. In addition, most of the compounds exhibited moderate antimicrobial activity against Gram-positive bacteria as well as fungal yeast, S. cervisiae. Comparison between 3 and 5 indicated that incorporation of additional substituted pyrazole nucleus into the scaffold significantly enhanced AI activity.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Antifúngicos/farmacologia , Domínio Catalítico/efeitos dos fármacos , Cumarínicos/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Edema/tratamento farmacológico , Simulação de Acoplamento Molecular , Tiazóis/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antifúngicos/síntese química , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Carragenina , Cumarínicos/síntese química , Cumarínicos/química , Ciclo-Oxigenase 1/química , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/química , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Masculino , Estrutura Molecular , Ratos , Ratos Wistar , Saccharomyces cerevisiae/efeitos dos fármacos , Relação Estrutura-Atividade , Tiazóis/síntese química , Tiazóis/química
15.
J Integr Med ; 11(6): 371-6, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24299601

RESUMO

Traditional medicine is a blend of information gathered over generations from various communities and cultures. Pinus roxburghii Sargent (Pinaceae) commonly known as "chir pine" is widely used in traditional and folkloric systems of medicine. The all parts of the plant are believed to possess medicinal qualities in Ayurvedic and Unani systems of medicine. In these traditional systems of medicine, the plant is used to heal many diseases, including afflictions of the eyes, ears, throat, blood, and skin. The plant parts are rich in various bioactive compounds such as α-pinene, abietic acid, quercetin and xanthone. Resin acids and flavanoid form a major portion of these bioactive compounds. This review presents examples of traditional medicinal uses for P. roxburghii, and subsequently explores the current understanding of the chemical, pharmacological, and biochemical properties of the extracts and the main active constituents found in each tissue of the plant. Clinical trial information is also included where available. Careful evaluation of these data may be helpful for scientists and researchers to discover and evaluate the specific chemical entities responsible for the traditional medicinal uses of P. roxburghii.


Assuntos
Etnobotânica , Fitoterapia , Pinus , Animais , Humanos , Pinus/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
16.
Eur J Med Chem ; 70: 350-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24177361

RESUMO

Searching for new anti-inflammatory agents, we have prepared a series of potential COX-2 inhibitors, 1-(4,6-dimethylpyrimidin-2-yl)-5-hydroxy-5-trifluoromethyl-Δ(2)-pyrazolines (3) and 1-(4,6-dimethylpyrimidin-2-yl)-3-trifluoromethylpyrazoles (4), by refluxing 2-hydrazino-4,6-dimethylpyrimidine (1) with a number of trifluoromethyl-ß-diketones (2) in ethanol. Further dehydration of compounds (3) to the corresponding 1-(4,6-dimethylpyrimidin-2-yl)-5-trifluoromethylpyrazoles (5) was also achieved. Fifteen of these compounds were screened for their anti-inflammatory activity using the carrageenan-induced rat paw edema assay. While all the compounds exhibited significant anti-inflammatory activity (47-76%) as compared to indomethacin (78%), 3-trifluoromethylpyrazoles (4) were found to be the most effective agents (62-76%). To rationalize this anti-inflammatory activity, docking experiments molecular dynamics simulations were performed to study the ability of these compounds to bind into the active site of the COX-2 enzyme.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Edema/tratamento farmacológico , Hidrocarbonetos Fluorados/farmacologia , Pirazóis/farmacologia , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/síntese química , Carragenina , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/síntese química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Hidrocarbonetos Fluorados/síntese química , Hidrocarbonetos Fluorados/química , Masculino , Modelos Moleculares , Pirazóis/síntese química , Pirazóis/química , Ratos , Ratos Wistar
17.
Bioorg Med Chem ; 21(15): 4581-90, 2013 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-23769654

RESUMO

Two series of celecoxib analogues having 1,5-diaryl relationship were synthesized. The key strategy of the molecular design was oriented towards exploring bioisosteric modifications of the sulfonamide moiety of celecoxib. First series (2a-2i) of celecoxib analogues bearing cyano functionality in place of sulfonamide moiety was synthesized by the reaction of appropriate trifluoromethyl-ß-diketones (5a-5i) with 4-hydrazinylbenzonitrile hydrochloride (4) in ethanol. Cyano moiety of pyrazoles 2 was then converted into corresponding carbothioamides 3 by bubbling H2S gas in the presence of triethylamine. All the synthesized compounds (2a-2i and 3a-3i) were screened for their in vivo anti-inflammatory (AI) activity using carrageenan-induced rat paw edema assay. COX-1 and COX-2 inhibitory potency was evaluated through in vitro cyclooxygenase (COX) assays. Compounds 2a, 2b, 2c, 2e and 3c showed promising AI activity at 3-4h after the carrageenan injection that was comparable to that of the standard drug indomethacin. Although compounds 3d, 3e and 3f exhibited more pronounced COX-2 inhibition but they also inhibit COX-1 effectively thus being less selective against COX-2. Three compounds 2a, 2f and 3a were found to have a COX profile comparable to the reference drug indomethacin. However 2e, 3b, 3c and 3i compounds were the most potent selective COX-2 inhibitors of this study with 3b showing the best COX-2 profile. In order to better rationalize the action and the binding mode of these compounds, docking studies were carried out. These studies were in agreement with the biological data.


Assuntos
Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase/síntese química , Pirazóis/síntese química , Pirazóis/farmacologia , Sulfonamidas/síntese química , Sulfonamidas/farmacologia , Animais , Celecoxib , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Desenho de Fármacos , Masculino , Pirazóis/química , Distribuição Aleatória , Ratos , Ratos Wistar , Sulfonamidas/química
18.
Eur J Med Chem ; 62: 508-14, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23416192

RESUMO

A series of novel 2-(5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-yl)-4-(coumarin-3-yl)thiazoles (6) were synthesized by condensing 3-(2-bromoacetyl)coumarins (4) with various 5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-thiocarboxamides (5), obtained by the reaction of thiosemicarbazide with trifluoromethyl-ß-diketones. All the tested compounds displayed significant to moderate in vivo anti-inflammatory activity when compared to the standard drug indomethacin, and good broad spectrum in vitro antibacterial activity against three Gram-positive and four Gram-negative bacteria when compared with cefixime.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Cumarínicos/farmacologia , Edema/tratamento farmacológico , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Tiazóis/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Cumarínicos/síntese química , Cumarínicos/química , Relação Dose-Resposta a Droga , Masculino , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Tiazóis/síntese química , Tiazóis/química
19.
Zhong Xi Yi Jie He Xue Bao ; 10(9): 1056-60, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22979938

RESUMO

OBJECTIVE: To study the anticonvulsant activity of alcoholic extract of bark of Pinus roxburghii Sarg. (AEPR) used in Indian traditional medicine system in treating convulsion. METHODS: Anticonvulsant activity was evaluated by maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced seizures in Wistar albino rats. In the MES model, 150 mA current for 0.2 s was given through ear electrodes to induce convulsions in rats. The duration of tonic extension of hind limb was used as the end point, namely, prevention or decrease in the duration of hind limb extension was considered as a protective action. In the PTZ model, the anticonvulsant property of AEPR was assessed by its ability to delay the onset of myoclonic spasm and clonic convulsions produced by intraperitoneal administration of PTZ. RESULTS: In the MES-induced seizure model, AEPR in doses of 300 and 500 mg/kg body weight reduced all the phases of convulsion significantly (P<0.01). Standard drug phenytoin at a dose of 25 mg/kg significantly reduced flexion phase (P<0.01) and abolished all phases of convulsion. In the PTZ-induced seizure model, the administration of the extract at doses of 300 and 500 mg/kg 30 min prior to injection of PTZ significantly delayed the onset of clonic seizure (P<0.01). AEPR at the dose of 100 mg/kg body weight could not exert any significant protective effect on PTZ-induced convulsions. Standard drug diazepam at a dose of 4 mg/kg showed much delayed onset of clonic seizure. CONCLUSION: The study suggests that AEPR would be effective against generalized tonic-clonic and partial seizures. Thus AEPR possesses anticonvulsant property against MES- and PTZ-induced seizures in Wistar rats. However, further research is in progress to isolate the compound responsible for its activity.


Assuntos
Anticonvulsivantes/farmacologia , Pinus/química , Extratos Vegetais/farmacologia , Convulsões/tratamento farmacológico , Animais , Anticonvulsivantes/uso terapêutico , Feminino , Masculino , Casca de Planta/química , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar
20.
Adv Pharmacol Sci ; 2012: 245431, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22761611

RESUMO

The Chir Pine, Pinus roxburghii, named after William Roxburgh, is a pine native to the Himalaya. Pinus roxburghii Sarg. (Pinaceae) is traditionally used for several medicinal purposes in India. As the oil of the plant is extensively used in number of herbal preparation for curing inflammatory disorders, the present study was undertaken to assess analgesic and anti-inflammatory activities of its bark extract. Dried and crushed leaves of Pinus roxburghii Sarg. were defatted with petroleum ether and then extracted with alcohol. The alcoholic extract at the doses of 100 mg/kg, 300 mg/kg, and 500 mg/kg body weight was subjected to evaluation of analgesic and anti-inflammatory activities in experimental animal models. Analgesic activity was evaluated by acetic acid-induced writhing and tail immersion tests in Swiss albino mice; acute and chronic anti-inflammatory activity was evaluated by carrageenan-induced paw oedema and cotton pellet granuloma in Wistar albino rats. Diclofenac sodium and indomethacin were employed as reference drugs for analgesic and anti-inflammatory studies, respectively. In the present study, the alcoholic bark extract of Pinus roxburghii Sarg. demonstrated significant analgesic and anti-inflammatory activities in the tested models.

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