The Chemical Scaffold of Theranostic Radiopharmaceuticals: Radionuclide, Bifunctional Chelator, and Pharmacokinetics Modifying Linker.

Therapeutic radiopharmaceuticals have been researched extensively in the last decade as a result of the growing research interest in personalized medicine to improve diagnostic accuracy and intensify intensive therapy while limiting side effects. Radiometal-based drugs are of substantial interest because of their greater versatility for clinical translation compared to non-metal radionuclides. This paper comprehensively discusses various components commonly used as chemical scaffolds to build radiopharmaceutical agents, i.e., radionuclides, pharmacokinetic-modifying linkers, and chelators, whose characteristics are explained and can be used as a guide for the researcher.

A systematic review: Molecular docking simulation of small molecules as anticancer non-small cell lung carcinoma drug candidates.

Non-small cell lung carcinoma (NSCLC) is a type of lung cancer with the highest prevalence and mortality rate worldwide. Many cases of this type of cancer are overexpression on epidermal growth factor receptor (EGFR). The use of currently available EGFR inhibitors as one of the treatment options for NSCLC still shows various shortcomings, especially the high failure rate of therapy due to resistance. It is important to find NSCLC drug candidates with EGFR inhibitory activity. There are various published articles and it is prominent to draw evidence-based scientific conclusions as a basis of decision-making to select potential compounds for further research. Polymer matrix composites and ScienceDirect are used as a database for article screening. Research using molecular docking method targeted to EGFR with parameters of Gibbs energy and amino acid interactions between ligands and drug targets are included in inclusion criteria. Compounds that achieve docking parameters and have comparable activity to NSCLC guideline drugs are conscientiously ranked. There are only 11 compounds that achieved the docking parameters and had comparable EGFR inhibitory potential. Top-rated compounds include 1,3,5-trisubstituted pyrazoline (3c), 1,3,5-trisubstituted pyrazoline (6c), 1,3,5-trisubstituted pyrazoline (8d), N-(3,4-Dimethylphenyl)-2-[(4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydrobenzo[g] quinazolin-2-yl) thio] acetamide. The top-rated compounds can be used and considered for further research processes.

Metabolomic Assay, Computational Screening, and Pharmacological Evaluation of Caulerpa racemosa as an Anti-obesity With Anti-aging by Altering Lipid Profile and Peroxisome Proliferator-Activated Receptor-γ Coactivator 1-α Levels.

Obesity is associated with an accelerated aging process, which prevents healthy aging. Both obesity and aging were manifested in the peroxisome proliferator-activated receptor-γ coactivator α (PGC-1α) level. These studies fulfill the scientific gap in assembled pharmacological activity assay of Caulerpa racemosa done in a previous preclinical trial. Six major compounds from sea grape (C. racemosa) extract were evaluated using an in silico approach against human pancreatic lipase, a-glucosidase, and a-amylase to predict prospective anti-obesity candidates. The lipase inhibitory activity of the extract reached 90.30 ± 0.40%, 1.75% lower than orlistat. The a-amylase inhibitory assay of the extract was 84.07 ± 5.28%, while the inhibitory activity against a-glucosidase was 81.67 ± 1.54%; both were lower than acarbose. We observe the effect of C. racemosa extract as anti-obesity with anti-aging by evaluating the obesity parameters in the human body for a 4-week period. There was a significant decrease in blood glucose, total cholesterol, low-density lipoprotein (LDL), triglycerides (TG), waist circumference, waist-hip ratio, and body weight (p < 0.05); PGC-1α and high-density lipoprotein (HDL) increased significantly (p = 0.000), in Group B when compared with Group A. Our study revealed that sea grape extract is a potent anti-obesity with an anti-aging reagent that does not produce any significant adverse effects.

The interaction of alpha-mangostin and its derivatives against main protease enzyme in COVID-19 using in silico methods.

More than 111 million people worldwide have been affected by the COVID-19 outbreak caused by SARS-CoV-2. The main therapeutic target of COVID-19 is main protease (Mpro). It plays a key role as an enzyme in the SARS-CoV-2 replication and transcription. In this case, the alpha-mangostin potentially has antiviral activity against Mpro by inhibiting this enzyme. Nevertheless, the alpha-mangostin has low solubility and a lack of information about alpha-mangostin activity against the SARS-CoV-2. The aim of this study is to describe the molecular interactions and identify the pharmacokinetics profile between alpha-mangostin and its derivatives. in silico study was conducted by pharmacokinetics and toxicity prediction, molecular docking simulation, and Lipinski's rule of five. FKS9 has a Gibbs free energy value of-10.5 kcal/mol with an inhibition constant of 36.45 µM and an interaction with amino acid His41 residue. Its human intestinal absorption and Caco-2 values were 95.13% and 47.71% while the plasma protein binding and blood-brain barrier values were 96.66% and 6.99%. FKS9 also has no mutagenic and carcinogenic potential. FKS9 as an alpha-mangostin derivative had the best interaction with the Mpro enzyme and its pharmacokinetic profiles was identified.

Sea grapes extract improves blood glucose, total cholesterol, and PGC-1α in rats fed on cholesterol- and fat-enriched diet.

Background: Sea grapes or  Caulerpa racemosa have a lot of phytochemical content, especially unsaturated fatty acids that are beneficial for health. This study aims to evaluate the effects of sea grapes extract on blood glucose levels, total cholesterol-, and Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α in male Wistar rats, which were given per-oral (p.o.) cholesterol- and carbohydrates fat-enriched diets (CFED). Methods: Forty male Wistar albino rats weighing between 200 - 250 g were used for this study. Animals were randomly distributed into four groups of ten animals each. Group A served as control (received standard dry pellet diet). Rats in group B were fed on CFED for 4 weeks.  Groups C and D were fed on CFED and were administered 150 and 450 mg/kg of  sea grapes extract (p.o.), respectively. Results: Group C rats indicated a blood glucose reduction and an increase in PGC-1α serum, in comparison to group D (p<0.05). There were no significant differences between group C and D in blood cholesterol reduction (high dose of the extract did not have significant effects) (p=0.222), and both groups had the same effect in lowering total cholesterol in rats.  Conclusion: Sea grapes extract is proven to improve blood glucose, total cholesterol, and PGC-1α levels in rats fed with CFED.