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1.
Chem Biol Interact ; 317: 108975, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032593

RESUMO

In patients with acute kidney injury progressively converting into chronic kidney disease (CKD), proteinuria and high blood pressure predict progression to end-stage renal disease (ESRD). Although, Renin-angiotensin-aldosterone system (RAAS) regulates blood pressure and kidney disease through both direct and indirect mechanisms. RAAS blockers that act at the level of angiotensin or lower in the cascade can cause compensatory increases in the plasma renin and angiotensin II level. Here, in this review article, we are exploring the evidence-based on RAAS blockade action releases of aldosterone and hypothesizing the molecular mechanism for converting the acute kidney injury into chronic kidney disease to end-stage renal disease.

2.
Drug Dev Res ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31785110

RESUMO

The well-known condition of heart failure is a clinical syndrome that results when the myocardium's ability to pump enough blood to meet the body's metabolic needs is impaired. Most of the cardiac activity is maintained by adrenoceptors, are categorized into two main α and ß and three distinct subtypes of ß receptor: ß1-, ß2-, and ß3-adrenoceptors. The ß adrenoreceptor is the main regulatory macro proteins, predominantly available on heart and responsible for down regulatory cardiac signaling. Moreover, the pathological involvement of Angiotensin-converting enzyme 1 (ACE1)/angiotensin II (Ang II)/angiotensin II type 1 (AT1) axis and beneficial ACE2/Ang (1-7)/Mas receptor axis also shows protective role via Gi ßγ, during heart failure these receptors get desensitized or internalized due to increase in the activity of G-protein-coupled receptor kinase 2 (GRK2) and GRK5, responsible for phosphorylation of G-protein-mediated down regulatory signaling. Here, we investigate the various clinical and preclinical data that exhibit the molecular mechanism of upset level of GRK change the cardiac activity during failing heart.

3.
J Environ Pathol Toxicol Oncol ; 38(2): 133-141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679276

RESUMO

The current study is a review of the literature on patients with diabetes who are diagnosed with colorectal cancer (CRC), encompassing recent research on CRC and the molecular level changes occurring in these patients on the basis of varying environmental as well as non-environmental factors. It has been noted that nearly 50% of all patients undergo the systemic treatment module; however, most of them exhibit drug resistance. In addition, targeted gene therapy has also been used in treatment but has been found to be effective only in patients with a specified molecular profile (or else this might lead to an increased risk of developing resistant mutations). This has led to increasing interest among researchers in finding innovative treatment options. Metformin, a biguanide, has been widely used in treating diabetes. The drug has been reportedly used in cases of hypothesis-generating retrospective population studies of diabetic patients showing reduced incidence of cancer. Metformin helps in reduction of excess insulin levels that possess various effects on cell signaling and metabolism. Nonetheless, there is need for an in-depth study on its molecular mechanism to fill any existing research gaps.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Neoplasias Colorretais/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Insulina/efeitos adversos , Transdução de Sinais/efeitos dos fármacos
4.
Iran J Pharm Res ; 18(2): 938-947, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531075

RESUMO

A new bioactive proline-rich cyclohexapeptide - diandrine C (6), previously isolated from whole plant of Drymaria diandra (Caryophyllaceae), was synthesized through coupling reactions of tetrapeptide unit Boc-Gly--Pro--Tyr--Trp-OH with dipeptide unit -Pro-Gly-OMe using N,N-diisopropylcarbodiimide (DIPC) as the coupling agent, followed by cyclization of linear hexapeptide unit under alkaline condition. Structure of cyclohexapeptide was confirmed by means of chemical, and spectroscopic analyses and also was screened for its antimicrobial and anthelmintic properties. Bioevaluation results indicated that the newly synthesized hexacyclopeptide exhibited potent antimicrobial activity against Gram-negative bacteria Pseudomonas aeruginosa, Klebsiella pneumoniae and pathogenic Candida albicans at 6 µg/mL. Moderate to good level of antihelmintic activity against three earthworm species Megascoplex konkanensis, Pontoscotex corethruses and Eudrilus eugeniae was also observed at concentration of 2 mg/mL.

5.
Int J Med Mushrooms ; 21(1): 29-35, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30806253

RESUMO

Auricularia polytricha is a popular mushroom found all over the world. This article describes a study of the antiepileptic effect of A. polytricha, a mushroom that is used traditionally for treating asthma, rheumatism, tumors, cough, fever, and epilepsy, and for its antimicrobial effect. We carried out toxicity studies to identify a standard dose of A. polytricha aqueous extract; maximal electroshock (MES)- and isoniazid (INH)-induced seizures in albino mice were used to screen for the extract's antiepileptic activity. Per Organisation for Economic Co-operation and Development Guideline 423, up to 2000 mg/kg body weight of extract was toxic. Animals were treated with aqueous extract at doses of 200, 400, and 600 mg/kg body weight. Phenytoin was used as the reference anticonvulsant drug for comparison. The investigation found a significant interruption in INH-induced clonic seizure. During MES, we found a reduction in the period of hind leg extensor phase; mice exhibited a significant decrease in the duration of hind limb extension after being treated with 400 and 600 mg/kg doses of A. polytricha. Comparable results were obtained in the INH group, as the extract seemed to delay the onset of a clonic seizure. The aqueous extract of A. polytricha showed antiepileptic action against MES- and INH-induced epilepsy in the mice. This extract, however, requires additional study in order to completely explain its active ingredients and their mechanisms of action.


Assuntos
Agaricales/química , Anticonvulsivantes/uso terapêutico , Produtos Biológicos/farmacologia , Eletrochoque/efeitos adversos , Isoniazida/toxicidade , Convulsões/tratamento farmacológico , Animais , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/química , Antituberculosos/toxicidade , Produtos Biológicos/efeitos adversos , Produtos Biológicos/química , Relação Dose-Resposta a Droga , Masculino , Camundongos , Fenitoína/administração & dosagem , Fenitoína/uso terapêutico , Água
6.
Biomed Pharmacother ; 108: 1188-1200, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30372820

RESUMO

BACKGROUND: Type 1 diabetes mellitus (T1DM) is an autoimmune disorder characterized by T cell-mediated self-destruction of insulin-secreting islet ß cells. Management of T1DM is challenging and complicated especially with conventional medications. Gene therapy has emerged as one of the potential therapeutic alternatives to treat T1DM. This review primarily focuses on the current status and the future perspectives of gene therapy in the management of T1DM. A vast number of the studies which are reported on gene therapy for the management of T1DM are done in animal models and in preclinical studies. In addition, the safety of such therapies is yet to be established in humans. Currently, there are several gene level interventions that are being investigated, notably, overexpression of genes and proteins needed against T1DM, transplantation of cells that express the genes against T1DM, stem-cells mediated gene therapy, genetic vaccination, immunological precursor cell-mediated gene therapy and vectors. METHODS: We searched the current literature through searchable online databases, journals and other library sources using relevant keywords and search parameters. Only relevant publications in English, between the years 2000 and 2018, with evidences and proper citations, were considered. The publications were then analyzed and segregated into several subtopics based on common words and content. A total of 126 studies were found suitable for this review. FINDINGS: Generally, the pros and cons of each of the gene-based therapies have been discussed based on the results collected from the literature. However, there are certain interventions that require further detailed studies to ensure their effectiveness. We have also highlighted the future direction and perspectives in gene therapy, which, researchers could benefit from.


Assuntos
Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/terapia , Terapia Genética , Animais , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 1/prevenção & controle , Engenharia Genética , Humanos , Imunoterapia , Vacinação
7.
Panminerva Med ; 60(3): 109-116, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30176701

RESUMO

Glioblastoma, also known as glioblastoma multiforme, is the most common and worldwide-spread cancer that begins within the brain. Glioblastomas represent 15% of brain tumors. The most common length of survival following diagnosis is 12 to 14 months with less than 3% to 5% of people surviving longer than five years. Without treatment, survival is typically 3 months. Among all receptors, special attention has been focused on the role of peroxisome proliferator-activated receptors (PPARs) in glioblastoma. PPARs are ligand-activated intracellular transcription factors. The PPAR subfamily consists of three subtypes encoded by distinct genes named PPARα, PPARß/δ, and PPARγ. PPARγ is the most extensively studied subtype of PPAR. There has been interesting preliminary evidence suggesting that diabetic patients receiving PPARγ agonists, a group of anti-diabetics, thiazolidinedione drugs, have an increased median survival for glioblastoma. In this paper, the recent progresses in understanding the potential mechanism of PPARγ in glioblastoma are summarized.


Assuntos
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , PPAR gama/agonistas , PPAR gama/metabolismo , Animais , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Glucose/química , Humanos , Insulina/metabolismo , Ligantes , Lipídeos/química , Camundongos , PPAR gama/química , Isoformas de Proteínas , Tiazolidinedionas/farmacologia , Fatores de Transcrição/metabolismo
8.
Mar Drugs ; 16(9)2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30200225

RESUMO

An N-methylated analog of a marine bacteria-derived natural proline-rich tetracyclopeptide was synthesized by coupling the deprotected dipeptide fragments Boc-l-prolyl-l-N-methylleucine-OH and l-prolyl-l-N-methylphenylalanine-OMe. A coupling reaction was accomplished utilizing N,N'-Dicyclohexylcarbodidimde (DCC) and 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC·HCl) as coupling agents and Triethylamine (TEA) or N-methylmorpholine (NMM) as the base in the presence of the racemization suppressing agent. This was followed by the cyclization of the linear tetrapeptide fragment under alkaline conditions. The structure of the synthesized cyclooligopeptide was confirmed using quantitative elemental analysis, FTIR (Fourier-transform infrared spectroscopy), ¹H NMR (Nuclear magnetic resonance spectroscopy), 13C NMR, and mass spectrometry. From the bioactivity results, it was clear that the newly synthesized proline-rich tetracyclopeptide exhibited better anthelmintic potential against Megascoplex konkanensis, Pontoscotex corethruses, and Eudrilus eugeniae at a concentration of 2 mg/mL as well as improved antifungal activity against pathogenic dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 µg/mL, as compared to non-methylated tetracyclopeptide. Moreover, N-methylated tetracyclopeptide displayed significant activity against pathogenic Candida albicans.


Assuntos
Organismos Aquáticos/química , Bactérias/química , Helmintos/efeitos dos fármacos , Peptídeos Cíclicos/síntese química , Animais , Anti-Helmínticos/síntese química , Anti-Helmínticos/farmacologia , Antibacterianos/síntese química , Antibacterianos/farmacologia , Antifúngicos/síntese química , Antifúngicos/farmacologia , Arthrodermataceae/efeitos dos fármacos , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Ciclização , Dipeptídeos/química , Metilação , Testes de Sensibilidade Microbiana , Estrutura Molecular , Peptídeos Cíclicos/farmacologia , Prolina/química , Espectroscopia de Infravermelho com Transformada de Fourier
10.
Int J Med Mushrooms ; 20(1): 81-88, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29604915

RESUMO

Auricularia polytricha is a popular mushroom found all over the world. In this study we considered the effect of an aqueous extract of A. polytricha (AEAP) on restoring sexual performance parameters to normal, evaluated by considering observations of sexual behavior. At 0, 6, 12, 18, and 24 days, the following parameters of sexual performance were identified before and throughout the observations: mount latency, intromission latency, ejaculation latency, mounting frequency, intromission frequency, ejaculation frequency, and postejaculatory interval. Treatment of rats under stress with AEAP showed promising effects on overcoming stress-induced sexual dysfunction, on sexual performance, and on accessory sexual organs and body weight. Mounting latency, intromission latency, ejaculation latency, and postejaculatory interval parameters were significantly decreased by AEAP, whereas mounting frequency, intromission frequency, and ejaculation frequency were significantly increased by AEAP. These properties were identified in sexually dynamic and indolent male rats. We conclude that AEAP has a potent aphrodisiac activity.


Assuntos
Agaricales/química , Afrodisíacos/administração & dosagem , Afrodisíacos/química , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Afrodisíacos/isolamento & purificação , Afrodisíacos/uso terapêutico , Feminino , Masculino , Ratos , Ratos Wistar , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Citrato de Sildenafila/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Água
11.
Iran J Pharm Res ; 16(3): 1176-1184, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29201105

RESUMO

The synthesis of a proline-rich cyclic heptapeptide, fanlizhicyclopeptide A (8), previously isolated from the fruits of Annona squamosa (sugar-apples), is described via coupling of tetrapeptide -prolyl--tyrosyl--leucyl--proline methyl ester with tripeptide Boc-glycyl--valyl--proline followed by cyclization of the linear fragment having seven amino acid units. Structure of the synthesized cyclooligopeptide was confirmed by the means of chemical and spectroscopic methods including FTIR, 1H NMR, 13C NMR, FABMS and further, subjected to the anthelmintic, antibacterial and the antifungal activity studies. Bioactivity results indicated that the newly synthesized cyclic peptide displayed potent anthelmintic activity against the three earthworm species Megascoplex konkanensis, Pontoscotex corethruses and Eudrilus eugeniae at 2 mg/mL and remarkable anti-dermatophytic activities against Trichophyton mentagrophytes and Microsporum audouinii at concentration of 6 µg/mL.

14.
Molecules ; 22(6)2017 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-28554994

RESUMO

The present investigation reports the synthesis of a phenylalanine-rich N-methylated cyclopeptide, cordyheptapeptide A (8), previously isolated from the insect pathogenic fungus Cordyceps sp. BCC 1788, accomplished through the coupling of N-methylated tetrapeptide and tripeptide fragments followed by cyclization of the linear heptapeptide unit. Structure elucidation of the newly synthesized cyclopolypeptide was performed by means of FT-IR, ¹H-NMR, 13C-NMR, and fast atom bombardment mass spectrometry (FABMS), and screened for its antibacterial, antidermatophytic, and cytotoxic potential. According to the antimicrobial activity results, the newly synthesized N-Methylated cyclopeptide exhibited potent antibacterial activity against Gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae and antifungal activity against dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 µg/mL, in comparison to the reference drugs, gatifloxacin and griseofulvin. In addition, cyclopolypeptide 8 displayed suitable levels of cytotoxicity against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines.


Assuntos
Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Fluoroquinolonas/farmacologia , Gatifloxacina , Griseofulvina/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Espectroscopia de Prótons por Ressonância Magnética , Pseudomonas aeruginosa/efeitos dos fármacos
15.
CNS Neurosci Ther ; 23(6): 457-461, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28417590

RESUMO

Alzheimer's disease (AD) is leading cause of death among older characterized by neurofibrillary tangles, oxidative stress, progressive neuronal deficits, and increased levels of amyloid-ß (Aß) peptides. Cholinergic treatment could be the best suitable physiological therapy for AD. Calcitonin gene-related peptide (CGRP) is a thirty-seven-amino acid regulatory neuropeptide resulting from different merging of the CGRP gene, which also includes adrenomedullin, amylin, calcitonin, intermedin, and calcitonin receptor-stimulating peptide. It is a proof for a CGRP receptor within nucleus accumbens of brain that is different from either the CGRP1 or CGRP2 receptor in which it demonstrates similar high-affinity binding for salmon calcitonin, CGRP, and amylin, a possession which is not shared by any extra CGRP receptors. Binding of CGRP to its receptor increases activated cAMP-dependent pkA and PI3 kinase, resulting in N-terminal fragments that are shown to exert complex inhibitory as well facilitator actions on nAChRs. Fragments such as CGRP1-4, CGRP1-5, and CGRP1-6 rapidly as well as reversibly improve agonist sensitivity of nAChRs without straight stimulating those receptors and produce the Ca2+ -induced intracellular Ca2+ mobilization. Renin-angiotensin-aldosterone system (RAAS)-activated angiotensin-type (AT4) receptor is also beneficial in AD. It has been suggested that exogenous administration of CGRP inhibits infiltration of macrophages and expression of various inflammatory mediators such as NFkB, IL-1b, TNF-α, iNOS, matrix metalloproteinase (MMP)-9, and cell adhesion molecules like intercellular adhesion molecule (ICAM)-1 which attenuates consequence of inflammation in AD. Donepezil, a ChEI, inhibits acetylcholinesterase and produces angiogenesis and neurogenesis, in the dentate gyrus of the hippocampus of WT mice after donepezil administration. However, none of the results discovered in CGRP-knockout mice and WT mice exposed to practical denervation. Therefore, selective agonists of CGRP receptors may become the potential candidates for treatment of AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/agonistas , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Doença de Alzheimer/genética , Animais , Peptídeo Relacionado com Gene de Calcitonina/genética , Humanos
16.
Nat Prod Commun ; 12(3): 379-383, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30549890

RESUMO

The solution-phase synthesis of a proline and glycine-rich plant-derived cyclic heptapeptide, gypsophin E (8), is reported via coupling of a tetrapeptide unit Glycyl-L-leucyl-L-valyl-L-proline-OMe with a tripeptide unit Boc-L-isoleucyl-glycyl-L-proline-OH, followed by cyclization of the linear fragment having seven amino acid units. The structure of the newly synthesized cycloheptapeptide was confirmed by means of chemical and spectroscopic methods. The newly synthesized cyclopolypeptide displayed potent antifungal and anthelmintic activities against the pathogenic yeast Candida albicans, the dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at the 6 µg/mL level, and the earthworms Megascoplex konkanensis, Pontoscotex corethruses and - - Eudrilus eugeniea at a concentration of 2 mg/mL.


Assuntos
Produtos Biológicos/síntese química , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/farmacologia , Animais , Anti-Helmínticos/síntese química , Anti-Helmínticos/farmacologia , Antifúngicos/síntese química , Antifúngicos/farmacologia , Produtos Biológicos/farmacologia , Fungos/efeitos dos fármacos , Estrutura Molecular , Oligoquetos/efeitos dos fármacos
17.
Acta Pol Pharm ; 74(3): 873-880, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-29513956

RESUMO

Synthesis of a proline-rich cyclic hexapeptide - diandrine A [VI] was accomplished by coupling of tetrapeptide unit Boc-Gly-Pro-Trp-Pro-OH with dipeptide unit Tyr-Phe-OMe followed by cyclization of linear peptide unit [V] under alkaline condition. Structure of newly synthesized cyclopolypeptide was elucidated by means of spectral techniques including FTIR, 'H NMR, "C NMR, MS analyses. VI was subjected to pharmacological screening and found to exhibit good antifungal activity against dermatophytes. Further, VI possessed potent antihelmintic activity against earthworms M. konkanensis, P. corthruses and Eudrilus sp.


Assuntos
Anti-Helmínticos/síntese química , Anti-Helmínticos/farmacologia , Antifúngicos/síntese química , Antifúngicos/farmacologia , Oligopeptídeos/síntese química , Oligopeptídeos/farmacologia , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/farmacologia , Animais , Arthrodermataceae/efeitos dos fármacos , Arthrodermataceae/crescimento & desenvolvimento , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Descoberta de Drogas/métodos , Espectrometria de Massas , Viabilidade Microbiana/efeitos dos fármacos , Estrutura Molecular , Oligoquetos/efeitos dos fármacos , Oligoquetos/crescimento & desenvolvimento , Testes de Sensibilidade Parasitária , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Relação Estrutura-Atividade , Tecnologia Farmacêutica/métodos
18.
Mar Drugs ; 14(12)2016 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-27983681

RESUMO

A natural heptacyclopeptide, stylissamide G (7), previously isolated from the Bahamian marine sponge Stylissa caribica from the Caribbean Sea, was synthesized via coupling of the tetrapeptide l-phenylalanyl-l-prolyl-l-phenylalanyl-l-proline methyl ester with the tripeptide Boc-l-leucyl-l-isoleucyl-l-proline, followed by cyclization of the linear heptapeptide fragment. The structure of the synthesized cyclooligopeptide was confirmed using quantitative elemental analysis, FT-IR, ¹H NMR, 13C NMR and mass spectrometry. Results of pharmacological activity studies indicated that the newly synthesized cycloheptapeptide displayed good anthelmintic potential against Megascoplex konkanensis, Pontoscotex corethruses and Eudrilus eugeniea at 2 mg/mL and in addition, potent antifungal activity against pathogenic Candida albicans and dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 µg/mL.


Assuntos
Peptídeos Cíclicos/química , Poríferos/química , Prolina/química , Animais , Anti-Helmínticos/química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Região do Caribe , Ciclização , Dipeptídeos/química , Espectroscopia de Ressonância Magnética/métodos , Testes de Sensibilidade Microbiana/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
19.
Mar Drugs ; 14(11)2016 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-27792168

RESUMO

Peptides have gained increased interest as therapeutics during recent years. More than 60 peptide drugs have reached the market for the benefit of patients and several hundreds of novel therapeutic peptides are in preclinical and clinical development. The key contributor to this success is the potent and specific, yet safe, mode of action of peptides. Among the wide range of biologically-active peptides, naturally-occurring marine-derived cyclopolypeptides exhibit a broad range of unusual and potent pharmacological activities. Because of their size and complexity, proline-rich cyclic peptides (PRCPs) occupy a crucial chemical space in drug discovery that may provide useful scaffolds for modulating more challenging biological targets, such as protein-protein interactions and allosteric binding sites. Diverse pharmacological activities of natural cyclic peptides from marine sponges, tunicates and cyanobacteria have encouraged efforts to develop cyclic peptides with well-known synthetic methods, including solid-phase and solution-phase techniques of peptide synthesis. The present review highlights the natural resources, unique structural features and the most relevant biological properties of proline-rich peptides of marine-origin, focusing on the potential therapeutic role that the PRCPs may play as a promising source of new peptide-based novel drugs.


Assuntos
Organismos Aquáticos/química , Produtos Biológicos/química , Produtos Biológicos/farmacocinética , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Prolina/química , Prolina/farmacologia , Animais , Cianobactérias/química , Descoberta de Drogas/métodos , Humanos , Poríferos/química , Urocordados/química
20.
Mar Drugs ; 8(8): 2384-94, 2010 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-20948913

RESUMO

The present study deals with the first total synthesis of the proline-rich cyclopolypeptide stylisin 2 via a solution phase technique by coupling of the Boc-L-Pro-L-Ile-L-Pro-OH tripeptide unit with the L-Phe-L-Pro-L-Pro-L-Tyr-OMe tetrapeptide unit, followed by cyclization of the resulting linear heptapeptide fragment. The chemical structure of the finally synthesized peptide was elucidated by FTIR, ¹H/¹³C-NMR and FAB MS spectral data, as well as elemental analyses. The newly synthesized peptide was subjected to antimicrobial screening against eight pathogenic microbes and found to exhibit potent antimicrobial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans, in addition to moderate antidermatophyte activity against pathogenic Trichophyton mentagrophytes and Microsporum audouinii when compared to standard drugs--gatifloxacin and griseofulvin.


Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Oligopeptídeos/síntese química , Oligopeptídeos/farmacologia , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Infecciosos/química , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Ciclização , Fungos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Oceanos e Mares , Oligopeptídeos/química , Peptídeos Cíclicos/análise
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