Pharmacological Aspects of 6-Gingerol: A Review

Habitual consumption of raw fruits as well as vegetables can trim down the threat of many diseases. Ginger is consumed globally as a cuisine and herbal medicine. It is rich in pungent phenolic phytochemical substances together called gingerols. 6-Gingerol (1-[4’-hydroxy-3’-methoxyphenyl]-5-hydroxy-3- decanone) is the chief pharmacologically-active moiety of ginger. Molecularly, gingerol is a relative of capsaicin and piperine, the compounds which are alkaloids, though the bioactive pathways are unconnected. It is normally found as pungent yellow oil in the ginger rhizome, but can also form a low-melting crystalline solid. Previous studies have suggested ample of therapeutic activities including anticancer, anti-inflammation and anti-oxidation. 6-Gingerol has been found to possess anticancer activities via its effect on a variety of biological pathways involved in apoptosis, cell cycle regulation, cytotoxic activity and inhibition of angiogenesis. Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, 6-gingerol has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various diseases. Overall, this review encapsulates different therapeutic and pharmacological facets of 6-gingerol along with its possible mechanism of action.

Quinazoline and its diverse array of therapeutic application:A review

Heterocyclic chemistry being an important branch of chemistry includes many ring structures with heteroatoms such as nitrogen, oxygen, and sulfur. Quinazoline is an important nitrogen containing benzofused heterocycle and has several therapeutic actions such as antimalarial, antimicrobial, anticancer, and anticonvulsant. Quinazoline was first isolated from alkaloid vasicine. Vasicine, deoxyvasicine, tryptanthrin, and rutecarpine are some of the potent naturally occurring quinazolines. Substitutions on different positions of quinazoline ring lead to different activities. Detailed survey of activities of quinazoline such as anticancer, anticonvulsant, antifungal, antibacterial, and antidiabetic according to structure–activity relationship and marketed preparations containing quinazoline as an active moiety is described in this review.

A Machine Learning Model to Predict Risperidone Active Moiety Concentration Based on Initial Therapeutic Drug Monitoring

Risperidone is an efficacious second-generation antipsychotic (SGA) to treat a wide spectrum of psychiatric diseases, whereas its active moiety (risperidone and 9-hydroxyrisperidone) concentration without a therapeutic reference range may increase the risk of adverse drug reactions. We aimed to establish a prediction model of risperidone active moiety concentration in the next therapeutic drug monitoring (TDM) based on the initial TDM information using machine learning methods. A total of 983 patients treated with risperidone between May 2017 and May 2018 in Beijing Anding Hospital were collected as the data set. Sixteen predictors (the initial TDM value, dosage, age, WBC, PLT, BUN, weight, BMI, prolactin, ALT, MECT, Cr, AST, Ccr, TDM interval, and RBC) were screened from 26 variables through univariate analysis (p < 0.05) and XGBoost (importance score >0). Ten algorithms (XGBoost, LightGBM, CatBoost, AdaBoost, Random Forest, support vector machine, lasso regression, ridge regression, linear regression, and k-nearest neighbor) compared the model performance, and ultimately, XGBoost was chosen to establish the prediction model. A cohort of 210 patients treated with risperidone between March 1, 2019, and May 31, 2019, in Beijing Anding Hospital was used to validate the model. Finally, the prediction model was evaluated, obtaining R2 (0.512 in test cohort; 0.374 in validation cohort), MAE (10.97 in test cohort; 12.07 in validation cohort), MSE (198.55 in test cohort; 324.15 in validation cohort), RMSE (14.09 in test cohort; 18.00 in validation cohort), and accuracy of the predicted TDM within ±30% of the actual TDM (54.82% in test cohort; 60.95% in validation cohort). The prediction model has promising performance to facilitate rational risperidone regimen on an individualized level and provide reference for other antipsychotic drugs' risk prediction.

Modulation by Phosphonium Ions of the Activity of Mitotropic Agents Based on the Chemiluminescence of Luminols

Mitochondria-targeting drugs and diagnostics are used in the monitoring and treatment of mitochondrial pathologies. In this respect, a great number of functional compounds have been made mitotropic by covalently attaching the active moiety onto a triphenylphosphonium (TPP) cation. Among these compounds, a number of molecular detectors for reactive oxygen species (ROS) are based on fluorescent and chemiluminescent probes. In this regard, luminol (probably the most widely known chemiluminescent molecule) has been employed for a number of biological applications, including ROS detection. Its oxidation under specific conditions triggers a cascade of reactions, ultimately leading to the excited 3-aminophthalate (3AP*), which emits light upon deactivation. Hence, the photophysical interaction between the light emitting species 3AP* and TPP cations needs to be evaluated, as it can add valuable information on the design of novel emission-based mitotropic systems. We herein investigate the quenching effect of ethyltriphenylphosphonium cation onto substituted 3-aminophthalates. These were prepared in situ upon the hydrolysis of the corresponding anhydrides, which were synthesized from 3-aminophthalimides. Steady-state fluorescence and time-resolved experiments were employed for the evaluation of a possible electron transfer quenching by phosphonium ions. Our experimental results confirmed such quenching, suggesting it is mainly dynamic in nature. A minor contribution of static quenching that was also detected is attributed to complex formation in the ground state. Accordingly, the chemiluminescence of luminol was indeed strongly reduced in the presence of phosphonium ions. Our results have to be taken into account during the design of new chemiluminescent mitotropic drugs or diagnostic agents of the luminol family.

Formulation and optimization of synthetic polymer based herbal emulgel for anti-microbial activity

The aim of the present research was to develop and evaluate the anti-microbial emulgel by using three different types of synthetic polymers. The active moiety selected for the formulation was the seeds of Carica papaya fruit. The formulation was developed by performing the extraction process; Soxhlet extraction with ethanol and water. The seeds of Carica papaya are reported to have anti-microbial properties. The skin-friendly i.e., the topical formulation was selected for development. Emulgel was prepared by incorporating different polymers and then evaluating each of them for best results. Basic evaluation parameters such as organoleptic parameters, viscosity, consistency, pH, homogeneity have been done, which demonstrate the results as per the reference and standard articles. Along with that, qualitative and quantitative tests of Carica seeds have also been performed, which indicates that the selected plant material is safe for usage. Finally, the most imp test, the anti-microbial test has been performed for determining the efficacy of prepared emulgel. Hence, it can be concluded that the prepared emulgel is safe and best for topical use as an anti-microbial.

Curcumin Nanoparticles as Promising Therapeutic Agents for Drug Targets

Curcuma longa is very well-known medicinal plant not only in the Asian hemisphere but also known across the globe for its therapeutic and medicinal benefits. The active moiety of Curcuma longa is curcumin and has gained importance in various treatments of various disorders such as antibacterial, antiprotozoal, cancer, obesity, diabetics and wound healing applications. Several techniques had been exploited as reported by researchers for increasing the therapeutic potential and its pharmacological activity. Here, the dictum is the new room for the development of physicochemical, as well as biological, studies for the efficacy in target specificity. Here, we discussed nanoformulation techniques, which lend support to upgrade the characters to the curcumin such as enhancing bioavailability, increasing solubility, modifying metabolisms, and target specificity, prolonged circulation, enhanced permeation. Our manuscript tried to seek the attention of the researcher by framing some solutions of some existing troubleshoots of this bioactive component for enhanced applications and making the formulations feasible at an industrial production scale. This manuscript focuses on recent inventions as well, which can further be implemented at the community level.

Manogepix, the Active Moiety of the Investigational Agent Fosmanogepix, Demonstrates In vitro Activity against Members of the Fusarium oxysporum and Fusarium solani Species Complexes

We evaluated the in vitro activity of manogepix against Fusarium oxysporum and Fusarium solani species complexes (FOSC and FSSC, respectively) isolates per CLSI M38 broth microdilution methods. Manogepix demonstrated activity against both FOSC (MEC range ≤0.015-0.03; MIC 50% growth inhibition range ≤0.015-0.125) and FSSC (≤0.015 μg/mL; ≤0.015-0.25 μg/mL). Amphotericin B was also active (MIC range 0.25-4 μg/mL), while the triazoles (1->16 μg/mL) and micafungin (MEC ≥8 μg/mL) had limited activity.