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1.
Front Cell Dev Biol ; 10: 984311, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36158215

RESUMO

Cancer is still one of the world's deadliest health concerns. As per latest statistics, lung, breast, liver, prostate, and cervical cancers are reported topmost worldwide. Although chemotherapy is most widely used methodology to treat cancer, poor pharmacokinetic parameters of anticancer drugs render them less effective. Novel nano-drug delivery systems have the caliber to improve the solubility and biocompatibility of various such chemical compounds. In this regard, cyclodextrins (CD), a group of natural nano-oligosaccharide possessing unique physicochemical characteristics has been highly exploited for drug delivery and other pharmaceutical purposes. Their cup-like structure and amphiphilic nature allows better accumulation of drugs, improved solubility, and stability, whereas CDs supramolecular chemical compatibility renders it to be highly receptive to various kinds of functionalization. Therefore combining physical, chemical, and bio-engineering approaches at nanoscale to specifically target the tumor cells can help in maximizing the tumor damage without harming non-malignant cells. Numerous combinations of CD nanocomposites were developed over the years, which employed photodynamic, photothermal therapy, chemotherapy, and hyperthermia methods, particularly targeting cancer cells. In this review, we discuss the vivid roles of cyclodextrin nanocomposites developed for the treatment and theranostics of most important cancers to highlight its clinical significance and potential as a medical tool.

2.
Molecules ; 27(3)2022 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-35164069

RESUMO

The human population is still facing appalling conditions due to several outbreaks of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus. The absence of specific drugs, appropriate vaccines for mutants, and knowledge of potential therapeutic agents makes this situation more difficult. Several 1, 2, 4-triazolo [1, 5-a] pyrimidine (TP)-derivative compounds were comprehensively studied for antiviral activities against RNA polymerase of HIV, HCV, and influenza viruses, and showed immense pharmacological interest. Therefore, TP-derivative compounds can be repurposed against the RNA-dependent RNA polymerase (RdRp) protein of SARS-CoV-2. In this study, a meta-analysis was performed to ensure the genomic variability and stability of the SARS-CoV-2 RdRp protein. The molecular docking of natural and synthetic TP compounds to RdRp and molecular dynamic (MD) simulations were performed to analyse the dynamic behaviour of TP compounds at the active site of the RdRp protein. TP compounds were also docked against other non-structural proteins (NSP1, NSP2, NSP3, NSP5, NSP8, NSP13, and NSP15) of SARS-CoV-2. Furthermore, the inhibition potential of TP compounds was compared with Remdesivir and Favipiravir drugs as a positive control. Additionally, TP compounds were analysed for inhibitory activity against SARS-CoV RdRp protein. This study demonstrates that TP analogues (monomethylated triazolopyrimidine and essramycin) represent potential lead molecules for designing an effective inhibitor to control viral replication. Furthermore, in vitro and in vivo studies will strengthen the use of these inhibitors as suitable drug candidates against SARS-CoV-2.


Assuntos
RNA-Polimerase RNA-Dependente de Coronavírus/efeitos dos fármacos , RNA-Polimerase RNA-Dependente de Coronavírus/metabolismo , Pirimidinas/farmacologia , Triazóis/farmacologia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Alanina/análogos & derivados , Alanina/farmacologia , Amidas/farmacologia , COVID-19/metabolismo , Domínio Catalítico/efeitos dos fármacos , Biologia Computacional/métodos , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Pirazinas/farmacologia , Pirimidinas/química , RNA Viral/efeitos dos fármacos , RNA Polimerase Dependente de RNA/efeitos dos fármacos , RNA Polimerase Dependente de RNA/metabolismo , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/metabolismo , Triazóis/química , Replicação Viral/efeitos dos fármacos , Tratamento Farmacológico da COVID-19
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