Investigators were continuously creating novel nanotechnologies to address unmet requirements throughout the administration of therapeutic medicines & imaging agents for cancer treatment & diagnostics, appropriately. LNPs(Lipid nanoparticles) are legitimate particulates (approx. 100 nm in size) gathered from various lipid as well as other biochemical compounds which overall functionality to resolve biological barriers (biobarriers), allowing LNPs to selectively collect somewhere outside of disease-target cells again for responsive therapeutics. Most pharmaceutically important compounds were insoluble throughout water solutions, were chemical & physiologically unstable, or have toxicities. Among the most potential drug carrier for bioactive organic compounds is LBNPs (Lipid based nanoparticles) technologies. Its present use in chemotherapy have transformed treatment for cancer by increasing the antitumor effect of a number of chemotherapeutics. Because they may be created using naturally occurring sources, LBNPs have great temporal and thermal stability, maximum load potential, simplicity of preparations, cheap manufacturing costs, & big manufacturing output. Furthermore, combining chemotherapeutic drugs with LNPs reduces active therapeutic dosage and toxicities, lowers treatment resistance, & raises drug concentration in tumour cells while reducing concentrations in normal tissue. LBNPs were widely studied in cancer treatment, both in vitro and in vivo, with encouraging outcomes in certain clinical trials. This study provides an overview of the many types of LBNPs which have been created in latest years and their applications and contributions in different types of cancers.
Extremophilic microorganisms often produce novel bioactive compounds to survive under harsh environmental conditions. Exopolysaccharides (EPSs), a constitutive part of bacterial biofilm, are functional biopolymers that act as a protecting sheath to the extremophilic bacteria and are of high industrial value. In this study, we elucidate a new EPS produced by thermophilic Bacillus haynesii CamB6 from a slightly acidic (pH 5.82) Campanario hot spring (56.4 °C) located in the Central Andean Mountains of Chile. Physicochemical properties of the EPS were characterized by different techniques: Scanning electron microscopy- energy dispersive X-ray spectroscopy (SEM-EDS), Atomic Force Microscopy (AFM), High-Performance Liquid Chromatography (HPLC), Gel permeation chromatography (GPC), Fourier Transform Infrared Spectroscopy (FTIR), 1D and 2D Nuclear Magnetic Resonance (NMR), and Thermogravimetric analysis (TGA). The EPS demonstrated amorphous surface roughness composed of evenly distributed macromolecular lumps. GPC and HPLC analysis showed that the EPS is a low molecular weight heteropolymer composed of mannose (66%), glucose (20%), and galactose (14%). FTIR analysis demonstrated the polysaccharide nature (–OH groups, Acetyl groups, and pyranosic ring structure) and the presence of different glycosidic linkages among sugar residues, which was further confirmed by NMR spectroscopic analyses. Moreover, D-mannose α-(1→2) and α-(1→4) linkages prevail in the CamB6 EPS structure. TGA revealed the high thermal stability (240 °C) of the polysaccharide. The functional properties of the EPS were evaluated for food industry applications, specifically as an antioxidant and for its emulsification, water-holding (WHC), oil-holding (OHC), and flocculation capacities. The results suggest that the study EPS can be a useful additive for the food-processing industry.
1 April 2019 in Asian Pacific Journal of Cancer Prevention
Breast cancer is the most frequent malignancy among women. It is a heterogeneous disease with different subtypesdefined by its hormone receptor. A hormone receptor is mainly concerned with the progression of the PI3K/AKT/mTOR pathway which is often dysregulated in breast cancer. This is a major signaling pathway that controls theactivities such as cell growth, cell division, and cell proliferation. The present study aims to suppress mTOR proteinby its various inhibitors and to select one with the highest binding affinity to the receptor protein. Out of 40 inhibitorsof mTOR against breast cancer, SF1126 was identified to have the best docking score of -8.705, using SchrodingerSuite which was further subjected for high throughput screening to obtain best similar compound using Lipinski’sfilters. The compound obtained after virtual screening, ID: ZINC85569445 is seen to have the highest affinity withthe target protein mTOR. The same result based on the binding free energy analysis using MM-GBSA showed thatthe compound ZINC85569445 to have the the highest binding free energy. The next study of interaction between theligand and receptor protein with the pharmacophore mapping showed the best conjugates, and the ZINC85569445 canbe further studied for future benefits of treatment of breast cancer.
1 May 2023 in American Journal of Physiology-Endocrinology and Metabolism
FGF21 is an endocrine hormone that controls key metabolic processes and induces the synthesis of glucose transporters, resulting in increased glucose absorption levels in fat cells. It is expressed in multiple metabolically active organs and tissues. FGF21 is also a powerful regulator of glucose homeostasis as a direct downregulating gene of peroxisome proliferator-activated receptor ( PPAR), which plays a role in regulating the activity of glucose and lipids. Attempts were made to understand various aspects related to FGF21, including properties like receptor binding and genomic linkage map, along with the information about the genes that function in the upregulation of FGF21 and how it, directly and indirectly, downregulates the genes that are vital in various metabolic pathways. Furthermore, various gene regulatory analyses on the specific gene concerning unique micro RNAs and long non-coding RNAs that target FGF21 and alter its functioning along with single-nucleotide polymorphisms (SNPs) were observed, that are the common cause of cell dysregulation, leading to different metabolic diseases and pathogenesis of cancer. Unique protein-protein interaction and cross talk between FGF21 and PPARγ shed light on their combined role in metabolic disorder-related regulatory activities. Its potential and unique role as an effective biomarker for various cardiovascular and metabolic disorders have also been highlighted. This study attempts to highlight the pleiotropic role of FGF21 activity following its overexpression and inhibition of cascades that results in the induction of obesity from diet and simultaneously signals adipocytes to absorb glucose and decrease triglyceride and blood sugar levels in diabetic models (after administration), rendering it a promising treatment for several metabolic and cardiovascular disorders.
1 August 2019 in Asian Pacific Journal of Cancer Prevention
Acute myeloid leukemia (AML) is symbolized by an increase in the number of myeloid cells in the bone marrow andan arrest in their maturation, frequently resulting in hematopoietic insufficiency (granulocytopenia, thrombocytopenia,or anemia) with or without leukocytosis either by a predominance of immature forms or a loss of normal hematopoiesis.IDH2 gene encodes for isocitrate dehydrogenase enzyme which is involved in the TCA cycle domino effect andconverts isocitrate to alpha-ketoglutarate. In the U.S, the annual incidence of AML progressively increases with ageto a peak of 12.6 per 100,000 adults of 65 years or older. Mutations in isocitrate dehydrogenase 2 (arginine 132) havebeen demonstrated to be recurrent gene alterations in acute myeloid leukemia (AML) by forming 2-Hydroxy alphaketoglutarate which, instead of participating in TCA cycle, accumulates to form AML. The current study approachesby molecular docking and virtual screening to elucidate inhibitor with superior affinity against IDH2 and achieve apharmacological profile. To obtain the best established drug Molegro Virtual Docker algorithm was executed. Thecompound AG-221 (Pub CID 71299339) having the high affinity score was subjected to similarity search to retrievethe drugs with similar properties. The virtual screened compound SCHEMBL16391748 (PubChem CID-117816179)shows high affinity for the protein. Comparative study and ADMET study for both the above compounds resulted inequivalent chemical properties. Virtual screened compound SCHEMBL16391748 (PubChem CID-117816179) showsthe lowest re-rank score. These drugs are identified as high potential IDH2 inhibitors and can halt AML when validatedthrough further In vitro screening.
27 August 2019 in Current Topics in Medicinal Chemistry
Background: Alzheimers Disease (AD) is a neurodegenerative disease which is characterized by the deposition of amyloid plaques in the brain- a concept supported by most of the researchers worldwide. The main component of the plaques being amyloid-beta (Aβ42) results from the sequential cleavage of Amyloid precursor protein (APP) by beta and gamma secretase. This present study intends to inhibit the formation of amyloid plaques by blocking the action of gamma secretase protein with Inhibitors (GSI). Methods: A number of Gamma Secretase Inhibitors (GSI) were targeted to the protein by molecular docking. The inhibitor having the best affinity was used as a subject for further virtual screening methods to obtain similar compounds. The generated compounds were docked again at the same docking site on the protein to find a compound with higher affinity to inhibit the protein. The highlights of virtually screened compound consisted of Pharmacophore Mapping of the docking site. These steps were followed by comparative assessments for both the compounds, obtained from the two aforesaid docking studies, which included interaction energy descriptors, ADMET profiling and PreADMET evaluations. Results: 111 GSI classified as azepines, sulfonamides and peptide isosteres were used in the study. By molecular docking an amorpholino-amide, compound (22), was identified to be the high affinity compound GSI along with its better interaction profiles.The virtually screened pubchem compound AKOS001083915 (CID:24462213) shows the best affinity with gamma secretase. Collective Pharmacophore mapping (H bonds, electrostatic profile, binding pattern and solvent accesibility) shows a stable interaction. The resulting ADMETand Descriptor values were nearly equivalent. Conclusion: These compounds identified herein hold a potential as Gamma Secretase inhibitors.According to PreADMET values the compound AKOS001083915 is effective and specific to the target protein. Its BOILED-egg plot analysis infers the compound permeable to blood brain barrier.Comparative study for both the compounds resulted in having nearly equivalent properties. These compounds have the capacity to inhibit the protein which is indirectly responsible for the formation of amyloid plaques and can be further put to in vitro pharmacokinetic and dynamic studies.