SUMMARY:The production of sophorolipids by Candida bombicola NRRL Y-17069 grown in a mixture of sunflower oil cake and crude soybean oil as economic substrates with different fermentation techniques was studied. The highest yield (49.5 g·100 g −1 substrates) was obtained from solid state fermentation after employing a new concept for extraction by methanol (E I) followed by ethyl acetate (E II), then partially purified with hexane (E III). The course of time of fermentation was also studied, and E I extracted of the 12 th day showed the minimum surface tension (45 mN·m −1 ) at a critical micelle dilution (CMD) of 10% concentration. The produced sophorolipids were characterized and confirmed by FTIR and 1 H NMR spectroscopy. The anticancer activity of the produced compounds was assessed against MCF-7, HepG2, A549, HCT116 cancer cell lines and the results revealed that E III and E IV (a mixture of E I & E III) act as promising anticancer agents in HepG2 and A549 by inhibiting urokinase and histone deacetylase activities.
KEYWORDS: Anticancer activity; Candida bombicola; Solid state fermentation; Sophorolipids; Soybean oil; Sunflower oilcakeRESUMEN: Producción, caracterización y actividad anticancerígena de soforolípidos producidos mediante fermentación en estado sólido con Candida bombicola de tortas de girasol y aceite de soja. Se estudió la producción de soforolípidos por Candida bombicola NRRL Y-17069 cultiva con diferentes técnicas de fermentación en una mezcla de torta de girasol y aceite de soja crudo, como sustratos económicos. El rendimiento más alto (49,5 g·100 g −1 de sustrato) se obtuvo por fermentación en estado sólido después de extraer con metanol (IE) seguido de acetato de etilo (EII), y de purificación parcial con hexano (EIII). También se estudió el tiempo de fermentación, considerando que el extracto IE de 12 días mostró una tensión superficial mínima (45 mN·m −1 ) a una dilución micelar crítica (CMD) de concentración 10 %. Los soforolípidos producidos se caracterizaron y se confirmaron mediante espectroscopia FTIR y RMN de 1 H. La actividad anticancerígena de los compuestos producidos se evaluó en células MCF-7, HepG2, A549, líneas celulares de cáncer de HCT116 y los resultados revelaron que EIII y EIV (una mezcla de EI y EIII) actúan como prometedores agentes anticancerígenos en HepG2 y A549 inhibiendo las actividades de uroquinasa e histona desacetilasa.
Accurate and efficient prediction of protein-ligand interactions has been a long-lasting dream of practitioners in drug discovery. The insufficient treatment of hydration is widely recognized to be a major limitation for accurate protein-ligand scoring. Using an integration of molecular dynamics simulations on thousands of protein structures with novel big-data analytics based on convolutional neural networks and deep Taylor decomposition, we consistently identify here three different patterns of hydration to be essential for protein-ligand interactions. In addition to desolvation and water-mediated interactions, the formation of enthalpically favorable networks of first-shell water molecules around solvent-exposed ligand moieties is identified to be essential for protein-ligand binding. Despite being currently neglected in drug discovery, this hydration phenomenon could lead to new avenues in optimizing the free energy of ligand binding. Application of deep neural networks incorporating hydration to docking provides 89% accuracy in binding pose ranking, an essential step for rational structure-based drug design.
Molecular dynamics (MD) simulations
allow for accurate prediction
of the thermodynamic profile of binding-site water molecules critical
for protein–ligand association. Whereas this hydration-site
profiling converges rapidly for solvent-exposed sites independent
of the initial water placement, an accurate and reliable placement
is required for water molecules in occluded binding sites. Here, we
present an accurate and efficient hydration-site prediction method
for occluded binding sites combining water placement based on 3D-RISM
and MD simulations using WATsite.
The impact that β-arrestin proteins have on G protein-coupled receptor trafficking, signaling and physiological behavior has gained much appreciation over the past decade. A number of studies have attributed the side effects associated with the use of naturally occurring and synthetic opioids, such as respiratory depression and constipation, to excessive recruitment of β-arrestin. These findings have led to the development of biased opioid small molecule agonists that do not recruit β-arrestin, activating only the canonical G protein pathway. Similar G protein-biased small molecule opioids have been found to occur in nature, particularly within kratom, and opioids within salvia have served as a template for the synthesis of other G protein-biased opioids. Here, we present the first report of naturally occurring peptides that selectively activate G protein signaling pathways at δ opioid receptors, but with minimal β-arrestin recruitment. Specifically, we find that rubiscolin peptides, which are produced as cleavage products of the plant protein rubisco, bind to and activate G protein signaling at δ opioid receptors. However, unlike the naturally occurring δ opioid peptides leuenkephalin and deltorphin II, the rubiscolin peptides only very weakly recruit β-arrestin 2 and have undetectable recruitment of β-arrestin 1 at the δ opioid receptor.
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