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1.
Molecules ; 26(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34500603

RESUMO

The past few decades have witnessed significant progress in anticancer drug discovery. Small molecules containing heterocyclic moieties have attracted considerable interest for designing new antitumor agents. Of these, the pyrimidine ring system is found in multitude of drug structures, and being the building unit of DNA and RNA makes it an attractive scaffold for the design and development of anticancer drugs. Currently, 22 pyrimidine-containing entities are approved for clinical use as anticancer drugs by the FDA. An exhaustive literature search indicates several publications and more than 59 patents from the year 2009 onwards on pyrimidine derivatives exhibiting potent antiproliferative activity. These pyrimidine derivatives exert their activity via diverse mechanisms, one of them being inhibition of protein kinases. Aurora kinase (AURK) and polo-like kinase (PLK) are protein kinases involved in the regulation of the cell cycle. Within the numerous pyrimidine-based small molecules developed as anticancer agents, this review focuses on the pyrimidine fused heterocyclic compounds modulating the AURK and PLK proteins in different phases of clinical trials as anticancer agents. This article aims to provide a comprehensive overview of synthetic strategies for the preparation of pyrimidine derivatives and their associated biological activity on AURK/PLK. It will also present an overview of the synthesis of the heterocyclic-2-aminopyrimidine, 4-aminopyrimidine and 2,4-diaminopyrimidine scaffolds, and one of the pharmacophores in AURK/PLK inhibitors is described systematically.


Assuntos
Aurora Quinases/antagonistas & inibidores , Proteínas de Ciclo Celular/antagonistas & inibidores , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Pirimidinas/síntese química , Pirimidinas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Descoberta de Drogas/métodos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
2.
Molecules ; 26(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200814

RESUMO

Multi-drug resistant pathogens are a rising danger for the future of mankind. Iodine (I2) is a centuries-old microbicide, but leads to skin discoloration, irritation, and uncontrolled iodine release. Plants rich in phytochemicals have a long history in basic health care. Aloe Vera Barbadensis Miller (AV) and Salvia officinalis L. (Sage) are effectively utilized against different ailments. Previously, we investigated the antimicrobial activities of smart triiodides and iodinated AV hybrids. In this work, we combined iodine with Sage extracts and pure AV gel with polyvinylpyrrolidone (PVP) as an encapsulating and stabilizing agent. Fourier transform infrared spectroscopy (FT-IR), Ultraviolet-visible spectroscopy (UV-Vis), Surface-Enhanced Raman Spectroscopy (SERS), microstructural analysis by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and X-Ray-Diffraction (XRD) analysis verified the composition of AV-PVP-Sage-I2. Antimicrobial properties were investigated by disc diffusion method against 10 reference microbial strains in comparison to gentamicin and nystatin. We impregnated surgical sutures with our biohybrid and tested their inhibitory effects. AV-PVP-Sage-I2 showed excellent to intermediate antimicrobial activity in discs and sutures. The iodine within the polymeric biomaterial AV-PVP-Sage-I2 and the synergistic action of the two plant extracts enhanced the microbial inhibition. Our compound has potential for use as an antifungal agent, disinfectant and coating material on sutures to prevent surgical site infections.


Assuntos
Antibacterianos/química , Antibacterianos/síntese química , Aloe/química , Antifúngicos/química , Gentamicinas/química , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura/métodos , Nistatina/química , Extratos Vegetais/química , Povidona/química , Salvia/química , Salvia officinalis/química , Espectrometria por Raios X/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X/métodos
3.
Polymers (Basel) ; 13(7)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33805240

RESUMO

The non-toxic inorganic antimicrobial agents iodine (I2) and copper (Cu) are interesting alternatives for biocidal applications. Iodine is broad-spectrum antimicrobial agent but its use is overshadowed by compound instability, uncontrolled iodine release and short-term effectiveness. These disadvantages can be reduced by forming complex-stabilized, polymeric polyiodides. In a facile, in-vitro synthesis we prepared the copper-pentaiodide complex [Cu(H2O)6(12-crown-4)5]I6 · 2I2, investigated its structure and antimicrobial properties. The chemical structure of the compound has been verified. We used agar well and disc-diffusion method assays against nine microbial reference strains in comparison to common antibiotics. The stable complex revealed excellent inhibition zones against C. albicans WDCM 00054, and strong antibacterial activities against several pathogens. [Cu(H2O)6(12-crown-4)5]I6 · 2I2 is a strong antimicrobial agent with an interesting crystal structure consisting of complexes located on an inversion center and surrounded by six 12-crown-4 molecules forming a cationic substructure. The six 12-crown-4 molecules form hydrogen bonds with the central Cu(H2O)6. The anionic substructure is a halogen bonded polymer which is formed by formal I5- repetition units. The topology of this chain-type polyiodide is unique. The I5- repetition units can be understood as a triodide anion connected to two iodine molecules.

4.
Int J Biol Macromol ; 181: 605-611, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33766591

RESUMO

The outbreaks of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in 2019, have highlighted the concerns about the lack of potential vaccines or antivirals approved for inhibition of CoVs infection. SARS-CoV-2 RNA dependent RNA polymerase (RdRp) which is almost preserved across different viral species can be a potential target for development of antiviral drugs, including nucleoside analogues (NA). However, ExoN proofreading activity of CoVs leads to their protection from several NAs. Therefore, potential platforms based on the development of efficient NAs with broad-spectrum efficacy against human CoVs should be explored. This study was then aimed to present an overview on the development of NAs-based drug repurposing for targeting SARS-CoV-2 RdRp by computational analysis. Afterwards, the clinical development of some NAs including Favipiravir, Sofosbuvir, Ribavirin, Tenofovir, and Remdesivir as potential inhibitors of RdRp, were surveyed. Overall, exploring broad-spectrum NAs as promising inhibitors of RdRp may provide useful information about the identification of potential antiviral repurposed drugs against SARS-CoV-2.


Assuntos
COVID-19/tratamento farmacológico , Nucleosídeos/farmacologia , RNA Polimerase Dependente de RNA/metabolismo , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/enzimologia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Alanina/análogos & derivados , Alanina/farmacologia , Antivirais/farmacologia , COVID-19/virologia , Biologia Computacional/métodos , Reposicionamento de Medicamentos/métodos , Humanos , Modelos Moleculares , RNA Polimerase Dependente de RNA/antagonistas & inibidores
5.
J Biomol Struct Dyn ; 39(10): 3771-3779, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32397906

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative representative of a severe respiratory illness resulted in widespread human infections and deaths in nearly all of the countries since late 2019. There is no therapeutic FDA-approved drug against SARS-CoV-2 infection, although a combination of anti-viral drugs is directly being practiced in some countries. A broad-spectrum of antiviral agents are being currently evaluated in clinical trials, and in this review, we specifically focus on the application of Remdesivir (RVD) as a potential anti-viral compound against Middle East respiratory syndrome (MERS) -CoV, SARS-CoV and SARS-CoV-2. First, we overview the general information about SARS-CoV-2, followed by application of RDV as a nucleotide analogue which can potentially inhibits RNA-dependent RNA polymerase of COVs. Afterwards, we discussed the kinetics of SARS- or MERS-CoV proliferation in animal models which is significantly different compared to that in humans. Finally, some ongoing challenges and future perspective on the application of RDV either alone or in combination with other anti-viral agents against CoVs infection were surveyed to determine the efficiency of RDV in preclinical trials. As a result, this paper provides crucial evidence of the potency of RDV to prevent SARS-CoV-2 infections.Communicated by Ramaswamy H. Sarma.


Assuntos
COVID-19 , RNA Polimerase Dependente de RNA , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Animais , Antivirais/farmacologia , COVID-19/tratamento farmacológico , Humanos , SARS-CoV-2
6.
J Biomol Struct Dyn ; 39(10): 3780-3786, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32397951

RESUMO

Researchers have reported some useful information about the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leading to CoV disease 2019 (COVID-19). Several studies have been performed in order to develop antiviral drugs, from which a few have been prescribed to patients. Also, several diagnostic tests have been designed to accelerate the process of identifying and treating COVID-19. It has been well-documented that the surface of host cells is covered by some receptors, known as angiotensin-converting enzyme 2 (ACE2), which mediates the binding and entry of CoV. After entering, the viral RNA interrupts the cell proliferation system to activate self-proliferation. However, having all the information about the outbreakof the SARS-COV-2, it is not still clear which factors determine the severity of lung and heart function impairment induced by COVID-19. A major step in exploring SARS-COV-2 pathogenesis is to determine the distribution of ACE2 in different tissues . In this review, the structure and origin of CoV, the role of ACE2 as a receptor of SARS-COV-2 on the surface of host cells, and the ACE2 distribution in different tissues with a focus on lung and cardiovascular system have been discussed. It was also revealed that acute and chronic cardiovascular diseases (CVDs) may result in the clinical severity of COVID-19. In conclusion, this review may provide useful information in developing some promising strategies to end up with a worldwide COVID-19 pandemic.Communicated by Ramaswamy H. Sarma.


Assuntos
COVID-19 , Pandemias , Enzima de Conversão de Angiotensina 2 , Humanos , Pulmão , Peptidil Dipeptidase A/genética , SARS-CoV-2
7.
Talanta ; 223(Pt 1): 121704, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33303154

RESUMO

The rapid outbreak of coronavirus disease 2019 (COVID-19) around the world is a tragic and shocking event that demonstrates the unpreparedness of humans to develop quick diagnostic platforms for novel infectious diseases. In fact, statistical reports of diagnostic tools show that their accuracy, specificity and sensitivity in the detection of COVID hampered by some challenges that can be eliminated by using nanoparticles (NPs). In this study, we aimed to present an overview on the most important ways to diagnose different kinds of viruses followed by the introduction of nanobiosensors. Afterward, some methods of COVID-19 detection such as imaging, laboratory and kit-based diagnostic tests are surveyed. Furthermore, nucleic acids/protein- and immunoglobulin (Ig)-based nanobiosensors for the COVID-19 detection infection are reviewed. Finally, current challenges and future perspective for the development of diagnostic or monitoring technologies in the control of COVID-19 are discussed to persuade the scientists in advancing their technologies beyond imagination. In conclusion, it can be deduced that as rapid COVID-19 detection infection can play a vital role in disease control and treatment, this review may be of great help for controlling the COVID-19 outbreak by providing some necessary information for the development of portable, accurate, selectable and simple nanobiosensors.


Assuntos
Técnicas Biossensoriais , COVID-19/diagnóstico , Nanotecnologia , Humanos , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade
8.
Talanta ; 224: 121805, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33379031

RESUMO

Researchers have recently introduced some artificial enzymes based on nanomaterials that show significant catalytic activity relative to native enzymes called nanozyme. These nanozymes show superior performance than conventional catalysts and are considered as fascinating candidates for introducing the next generation of biomaterials in various industrial and biomedical fields. Recently, nanozymes have received a great deal of attention in biomedical applications due to their potential properties such as long-term stability, low cost, mass production capability, and controllable catalytic activity. Due to the intrinsic catalytic activity of nanoparticles (NPs) as nanozymes and their ability to be regulated in biomedical processes, this review paper focuses on the in vivo applications of nanozymes in biosensing and therapeutic activities. Despite the challenges and benefits of each approach, this paper attempts to provide an appropriate motivation for the classification of different nanozymes followed by their application in biomedical activities including in vivo biosensing and therapeutic potential in cancer, inflammation and microbial infections. Finally, some ongoing challenges and future perspective of nanozymes in biomedical application were surveyed. In conclusion, this paper may provide useful information regarding the development of nanozymes as promising platforms in biomedical settings due to expedited diagnosis, the advancement of multifactorial therapies and their pronounced stability.


Assuntos
Nanopartículas , Nanoestruturas , Neoplasias , Catálise , Humanos , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico
9.
Biomimetics (Basel) ; 5(3)2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32957469

RESUMO

Antibiotic resistance is an eminent threat for the survival of mankind. Nosocomial infections caused by multidrug resistant microorganisms are a reason for morbidity and mortality worldwide. Plant-based antimicrobial agents are based on synergistic mechanisms which prevent resistance and have been used for centuries against ailments. We suggest the use of cost-effective, eco-friendly Aloe Vera Barbadensis Miller (AV)-iodine biomaterials as a new generation of antimicrobial agents. In a facile, one-pot synthesis, we encapsulated fresh AV gel with polyvinylpyrrolidone (PVP) as a stabilizing agent and incorporated iodine moieties in the form of iodine (I2) and sodium iodide (NaI) into the polymer matrix. Ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), x-ray diffraction (XRD), microstructural analysis by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) verified the composition of AV-PVP-I2, AV-PVP-I2-NaI. AV, AV-PVP, AV-PVP-I2, AV-PVP-I2-NaI, and AV-PVP-NaI were tested in-vitro by disc diffusion assay and dip-coated on polyglycolic acid (PGA) sutures against ten microbial reference strains. All the tested pathogens were more susceptible towards AV-PVP-I2 due to the inclusion of "smart" triiodides with halogen bonding in vitro and on dip-coated sutures. The biocomplexes AV-PVP-I2, AV-PVP-I2-NaI showed remarkable antimicrobial properties. "Smart" biohybrids with triiodide inclusions have excellent antifungal and promising antimicrobial activities, with potential use against surgical site infections (SSI) and as disinfecting agents.

10.
Biomed Pharmacother ; 130: 110559, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32768882

RESUMO

As the number of people infected with the newly identified 2019 novel coronavirus (SARS-CoV2) is continuously increasing every day, development of potential therapeutic platforms is vital. Based on the comparatively high similarity of receptor-binding domain (RBD) in SARS-CoV2 and SARS-CoV, it seems crucial to assay the cross-reactivity of anti-SARS-CoV monoclonal antibodies (mAbs) with SARS-CoV2 spike (S)-protein. Indeed, developing mAbs targeting SARS-CoV2 S-protein RBD could show novel applications for rapid and sensitive development of potential epitope-specific vaccines (ESV). Herein, we present an overview on the discovery of new CoV followed by some explanation on the SARS-CoV2 S-protein RBD site. Furthermore, we surveyed the novel therapeutic mAbs for targeting S-protein RBD such as S230, 80R, F26G18, F26G19, CR3014, CR3022, M396, and S230.15. Afterwards, the mechanism of interaction of RBD and different mAbs were explained and it was suggested that one of the SARS-CoV-specific human mAbs, namely CR3022, could show the highest binding affinity with SARS-CoV2 S-protein RBD. Finally, some ongoing challenges and future prospects for rapid and sensitive advancement of therapeutic mAbs targeting S-protein RBD were discussed. In conclusion, it may be proposed that this review may pave the way for recognition of RBD and different mAbs to develop potential therapeutic ESV.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Pandemias , Pneumonia Viral/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Sequência de Aminoácidos , Anticorpos Monoclonais/química , Anticorpos Monoclonais/metabolismo , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/química , Anticorpos Antivirais/metabolismo , Afinidade de Anticorpos , Reações Antígeno-Anticorpo , Antígenos Virais/metabolismo , Sítios de Ligação de Anticorpos , COVID-19 , Vacinas contra COVID-19 , Coronavirus/química , Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Epitopos/imunologia , Humanos , Modelos Moleculares , Filogenia , Ligação Proteica , Conformação Proteica , Domínios Proteicos , SARS-CoV-2 , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Vacinas Virais/imunologia
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