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1.
Molecules ; 27(24)2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36558055

RESUMEN

This research work focuses on the potential application of an organic compound, santalol, obtained from santalum album, in the inhibition of the enzyme tyrosinase, which is actively involved in the biosynthesis of melanin pigment. Over-production of melanin causes undesirable pigmentation in humans as well as other organisms and significantly downgrades their aesthetic value. The study is designed to explain the purification of tyrosinase from the mushroom Agaricus bisporus, followed by activity assays and enzyme kinetics to give insight into the santalol-modulated tyrosinase inhibition in a dose-dependent manner. The multi-spectroscopic techniques such as UV-vis, fluorescence, and isothermal calorimetry are employed to deduce the efficiency of santalol as a potential candidate against tyrosinase enzyme activity. Experimental results are further verified by molecular docking. Santalol, derived from the essential oils of santalum album, has been widely used as a remedy for skin disorders and a potion for a fair complexion since ancient times. Based on enzyme kinetics and biophysical characterization, this is the first scientific evidence where santalol inhibits tyrosinase, and santalol may be employed in the agriculture, food, and cosmetic industries to prevent excess melanin formation or browning.


Asunto(s)
Melaninas , Monofenol Monooxigenasa , Humanos , Simulación del Acoplamiento Molecular , Sesquiterpenos Policíclicos , Inhibidores Enzimáticos/química
2.
Pharmaceutics ; 14(12)2022 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-36559149

RESUMEN

Mitochondria are implicated in a wide range of functions apart from ATP generation, and, therefore, constitute one of the most important organelles of cell. Since healthy mitochondria are essential for proper cellular functioning and survival, mitochondrial dysfunction may lead to various pathologies. Mitochondria are considered a novel and promising therapeutic target for the diagnosis, treatment, and prevention of various human diseases including metabolic disorders, cancer, and neurodegenerative diseases. For mitochondria-targeted therapy, there is a need to develop an effective drug delivery approach, owing to the mitochondrial special bilayer structure through which therapeutic molecules undergo multiple difficulties in reaching the core. In recent years, various nanoformulations have been designed such as polymeric nanoparticles, liposomes, inorganic nanoparticles conjugate with mitochondriotropic moieties such as mitochondria-penetrating peptides (MPPs), triphenylphosphonium (TPP), dequalinium (DQA), and mitochondrial protein import machinery for overcoming barriers involved in targeting mitochondria. The current approaches used for mitochondria-targeted drug delivery have provided promising ways to overcome the challenges associated with targeted-drug delivery. Herein, we review the research from past years to the current scenario that has identified mitochondrial dysfunction as a major contributor to the pathophysiology of various diseases. Furthermore, we discuss the recent advancements in mitochondria-targeted drug delivery strategies for the pathologies associated with mitochondrial dysfunction.

3.
Int J Biol Macromol ; 161: 271-281, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32512089

RESUMEN

SARS-CoV-2 has a positive sense RNA genome of 29.9 kb in size, showing high sequence similarity to the BAT-CoV, SARS-CoV, MERS-CoV. SARS-CoV-2 is composed of 14 open reading frames (ORFs), which encodes for a total of 27 proteins divided into structural and non-structural proteins (NSPs). The fundamental structural protein-encoding genes are a spike protein (S) gene, envelope protein (E) gene, a membrane protein (M) gene, and a nucleocapsid protein (N) gene. They make about 33% of the entire genome and are vital for the viral life cycle. Rest 67% is distributed among different NSPs (such as Mpro, helicase, and RNA-dependent RNA polymerase) encoding genes across the ORFs, which are involved in virus-cell receptor interactions during viral entry. Researchers are trying to formulate vaccines, therapeutic antibodies or protein-targeted antiviral drugs to control the spread. This review proceeds stepwise through the COVID-19 outbreak, structural and genomic organization, entry mechanism, pathogenesis, and finally highlighting the essential proteins involved at each step that might be potential targets for drug discovery. Currently, approved treatment modalities consist of only supportive care and oxygen supplementation. This review is established on the current knowledge that has expanded on structural motifs and topology of proteins and their functions.


Asunto(s)
Coronavirus/fisiología , Proteínas Virales/química , Proteínas Virales/genética , Antivirales/farmacología , Betacoronavirus/efectos de los fármacos , Betacoronavirus/genética , Betacoronavirus/fisiología , COVID-19 , Coronavirus/efectos de los fármacos , Coronavirus/genética , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Proteínas de la Nucleocápside de Coronavirus , Descubrimiento de Drogas , Genoma Viral , Humanos , Modelos Moleculares , Proteínas de la Nucleocápside/química , Proteínas de la Nucleocápside/genética , Sistemas de Lectura Abierta , Pandemias , Fosfoproteínas , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/transmisión , Neumonía Viral/virología , Conformación Proteica , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Internalización del Virus
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