The Chemical Modification to Improve Solubility of Chitosan and Its Derivatives Application, Preparation Method, Toxicity as a Nanoparticles.

Chitosan is a functional polymer in the pharmaceutical field, including for nanoparticle drug delivery systems. Chitosan-based nanoparticles are a promising carrier for a wide range of therapeutic agents and can be administered in various routes. Solubility is the main problem for its production and utilization in large-scale industries. Chitosan modifications have been employed to enhance its solubility, including chemical modification. Many reviews have reported the chemical modification but have not focused on the specific characteristics obtained. This review focused on the modification to improve chitosan solubility. Additionally, this review also focused on the application of chitosan derivatives in nanoparticle drug delivery systems since very few similar reviews have been reported. The specific method for chitosan derivative-based nanoparticles was also reported and the latest report of chitosan, chitosan derivative, and chitosan toxicity were also described.

Antibacterial Potency of an Active Compound from Sansevieria trifasciata Prain: An Integrated In Vitro and In Silico Study.

Sansevieria trifasciata Prain holds great potential as a valuable asset in pharmaceutical development. In this study, our focus is to explore and assess the antibacterial activity of various components derived from this plant, including extracts, fractions, subfractions, and isolates, explicitly targeting two common bacteria: Escherichia coli and Streptococcus aureus. The isolated compound, identified as a derivative pyridone alkaloid (5-methyl-11-(2-oxopyridin-1(2H)-yl)undecaneperoxoicacid), demonstrates notable antibacterial effects. The extracts, fractions, subfractions, and isolates reveal significant bacterial growth reductions (p < 0.05). The minimum inhibitory concentration (MIC) values for Escherichia coli were 1.95 ppm, 3.9 ppm, 15.62 ppm, and 7.81 ppm, respectively, while the MIC values for Streptococcus aureus were 1.95 ppm, 1.95 ppm, 15.62 ppm, and 7.81 ppm, respectively. Computational analysis showed the isolates' interaction with key residues on the active site of ß-ketoacyl-ACP synthase from Escherichia coli and TyrRS from Streptococcus aureus. The findings indicate that the isolates exhibit a strong affinity for specific residues, including His333, Cys163, and Phe392 in ß-ketoacyl-ACP synthase, as well as Arg88, His117, Glu160, and Gln213 in TyrRS. Comparative energy calculations using MMPBSA demonstrate the isolates' favorable binding energy (-104,101 kJ/mol for ß-ketoacyl-ACP synthase and -81,060 kJ/mol for TyrRS) compared to ciprofloxacin. The elucidated antibacterial activity and molecular interactions of the isolates present valuable knowledge for future in vitro studies, facilitating the development of novel antibacterial agents targeting diverse bacterial strains.

Anti-Alopecia Activity of Coumarin Derivatives Isolated from Merremia peltata Leaves and Computational Study of Their Binding to Androgen Receptors Using Molecular Docking and Molecular Dynamic Simulation.

Alopecia is a condition in which hair on the scalp or other areas of the body is lost or falls out excessively. Nutritional deficiency causes blood flow to the head to decrease causing the hormone testosterone to be changed by the enzyme 5-α-reductase to dihydrotestosterone, which inhibits the growth phase and accelerates the death phase. One of the methods developed to treat alopecia is through inhibition of the 5-α-reductase enzyme, which converts testosterone to its more potent metabolite, dihydrotestosterone (DHT). Ethnomedicinally, Merremia peltata leaf is used by the people of Sulawesi as a remedy for baldness. Therefore, in this research, an in vivo study was conducted on rabbits to determine the anti-alopecia activity of M. peltata leaf compounds. The structure of the compounds isolated from the M. peltata leaf ethyl acetate fraction was determined by analysis of NMR and LC-MS data. An in silico study was then carried out using minoxidil as a comparison ligand; scopolin (1) and scopoletin (2) isolated from M. peltata leaf were identified as anti-alopecia compounds by predicting docking, simulating molecular dynamics and predicting absorption, distribution, metabolism, excretion, and toxicology (ADME-Tox). Compounds 1 and 2 had a better effect on hair growth compared to positive controls, and NMR and LC-MS analysis showed that they had comparable binding energies to receptors in the molecular docking interaction study: -4.51 and -4.65 kcal/mol, respectively, compared to -4.8 kcal/mol for minoxidil. Molecular dynamics simulation analysis with the parameters binding free energy calculated using the MM-PBSA method and complex stability based on SASA, PCA, RMSD, and RMSF showed that scopolin (1) has a good affinity for androgens receptors. The ADME-Tox prediction for scopolin (1) showed good results for the parameters of skin permeability, absorption and distribution. Therefore, scopolin (1) is a potential antagonist to androgen receptors and could be useful in the treatment of alopecia.

Production of Low Molecular Weight Chitosan Using a Combination of Weak Acid and Ultrasonication Methods.

Low molecular weight chitosan (LMWC) has higher solubility and lower viscosity allowing for a wider pharmaceutical application compared to high molecular weight chitosan. LMWC chitosan can be obtained through a chitosan depolymerization process. This research aimed to produce LWMC using the combination of formic acid and ultrasonication method with the optimal condition of the depolymerization process. The chitosan depolymerization method was performed by combining formic acid and ultrasonication. The optimum conditions of the depolymerization process were obtained using the Box-Behnken design. The LMWC obtained from depolymerization was characterized to identify its yield, degree of deacetylation, the molecular weight, structure, morphology, thermal behavior, and crystallinity index. Results: The characterization results of LWMC obtained from the depolymerization process using the optimum conditions showed that the yield was 89.398%; the degree of deacetylation was 98.076%; the molecular weight was 32.814 kDa; there was no change in the chemical structure, LWMC had disorganized shape, there was no change in the thermal behavior, and LWMC had a more amorphous shape compared to native chitosan. Conclusion: The production of LWMC involving depolymerization in the presence of weak acid and ultrasonication can be developed by using the optimal condition of the depolymerization process.

Active Antialopecia Chemical Identification of Merremia peltata Leaves and Computational Study toward Androgen Receptor Using Molecular Docking and Molecular Dynamic Simulation.

Alopecia is a health condition in which the hair loses its function in some or all of the body. Alopecia occurs due to various genetic, environmental, and nutritional factors. One of the methods developed to treat alopecia is through inhibition of the enzyme 5-α-reductase, which converts testosterone into its more potent metabolite, dihydrotestosterone (DHT). In ethnomedicine, the leaves of Merremia peltata are used by the people of Sulawesi as a remedy for baldness. Therefore, in this study, an in vivo study was conducted on rabbits to investigate the antialopecia activity of the ethanolic extract of M. peltata leaves. The purified M. peltata leaf extract was fractionated using vacuum liquid chromatography with several solvents to produce fractions F1-F5. Each fraction was then retested in vivo in rabbits, and its content was then analyzed by LC-MS. An in silico study was then carried out using minoxidil as a comparison ligand; 17 compounds derived from M. peltata leaves were identified as antialopecia compounds through prediction of molecular interactions and molecular dynamics simulation and prediction of absorption, distribution, metabolism, excretion, and toxicology (ADME-Tox). The assay results showed that fractions F2 and F3 had a better effect on hair growth compared to the positive control, and the test compound obtained from the LC-MS analysis, bufotalinin, had a strong binding energy to the receptor in the molecular docking interaction study: -5.99 kcal/mol compared to -4.8 kcal/mol for minoxidil. Molecular dynamics simulation analysis with complex stability parameters based on solvent-accessible surface area (SASA), principal component analysis (PCA), root mean square deviation (RMSD), and root mean square fluctuation (RMSF) showed that bufotalinin has good affinity for androgen receptors. ADME-Tox prediction for bufotalinin showed good results for the parameters of skin permeability, absorption, and distribution. Therefore, bufotalinin, a steroid compound, is a potential androgen receptor antagonist and could be useful in the treatment of alopecia.

Unrevealing the Potential of Sansevieria trifasciata Prain Fraction for the Treatment of Androgenetic Alopecia by Inhibiting Androgen Receptors Based on LC-MS/MS Analysis, and In-Silico Studies.

Androgenetic Alopecia (AGA) occurs due to over-response to androgens causing severe hair loss on the scalp, and requires the development of new and efficient drugs to treat this condition. This study explores and identifies secondary metabolites from Sansevieriatrifasciata Prain using the LC-MS/MS and in-silico method. The inhibitory activity of bioactive compounds from S. trifasciata Prain against androgen receptors (PDB ID: 4K7A) was evaluated molecularly using docking and dynamics studies by comparing their binding energies, interactions, and stability with minoxidil. The results of the LC-MS/MS analysis identified Methyl pyrophaeophorbide A (1), Oliveramine (2), (2S)-3', 4'-Methylenedioxy-5, 7-dimethoxyflavane (3), 1-Acetyl-ß-carboline (4), Digiprolactone (5), Trichosanic acid (6) and Methyl gallate (7) from the leaves subfraction of this plant. Three alkaloid compounds (compounds 1, 3, and 4), and one flavonoid (compound 2), had lower docking scores of -7.0, -5.8, -5.2, and -6.3 kcal/mol, respectively. The prediction of binding energy using the MM-PBSA approach ensured that the potency of the four compounds was better than minoxidil, with energies of -66.13, -59.36, -40.39, and -40.25 kJ/mol for compounds 1, 3, 2, and 4, respectively. The dynamics simulation shows the stability of compound 1 based on the trajectory analysis for the 100 ns simulation. This research succeeded in identifying the compound and assessing the anti-alopecia activity of Sansevieria trifasciata Prain. Seven compounds were identified as new compounds never reported in Sansevieria trifasciata Prain. Four compounds were predicted to have better anti-alopecia activity than minoxidil in inhibiting androgen receptors through an in silico approach.

The Search for Cyclooxygenase-2 (COX-2) Inhibitors for the Treatment of Inflammation Disease: An in-silico Study.

Purpose: Cyclooxygenase (COX-2) has been validated as a molecular target for treating inflammatory diseases. The present work was performed to identify potential COX-2 inhibitors by employing pharmacophore modeling. Methods: The pharmacophore features consisted of seven features, ie, three hydrophobic, one negative ion, and three hydrogen bond acceptors, which were developed based on the structure of COX-2 inhibitor, (R)-naproxen. Results: The pharmacophore model was validated with a Goodness of Hit (GH score) of 0.754 and the values of AUC100% 0.51. Screening against the ZINC database retrieved 1675 hits, while the molecular docking procedure identified four best hit molecules in term of binding orientation and binding energies, ie, Lig_1805/ZINC103584272 (E = -11.03 kcal/mol), Lig_553/ZINC408573132 (E = -10.92 kcal/mol), Lig_680/ZINC103584263 (E = -10.90 kcal/mol), and Lig_2006/ZINC19324645 (E = -10.62 kcal/mol). Conclusion: The interactions of the four hits occurred in the binding site as (R)-naproxen did, and interestingly, their binding affinities were stronger than (R)-naproxen, implying their potential as COX-2 inhibitors.

Molecular docking studies and ADME-Tox prediction of phytocompounds from Merremia peltata as a potential anti-alopecia treatment.

Alopecia is a condition in which some or all of the hair from the scalp is lost. One recent preventative measure is the inhibition of the enzyme 5-α-reductase. Inhibition of the enzyme 5-α-reductase converts circulating testosterone to its more potent metabolite, dihydrotestosterone. Ethnobotically, Merremia peltata is used as a baldness medicine by utilising compounds contained within the leaves. This research aimed to test activity of 18 known compounds contained within M. peltata) as anti-alopecia. Activity was based on their interaction with the androgen receptor (PDB code 4K7a) using molecular docking and ADME-Tox prediction. The stages of research performed were: preparation of androgen protein structure databases; preparation and optimization of three-dimensional structures of compounds using ChemDraw 8.0; molecular docking to the androgen receptor protein using Autodock 1.5.6.; and ADME-Tox prediction using the pkCSM tool. The following test compounds had strong bond energies (ΔG): compound 16 (olean-12-en-3beta-ol, cinnamate)-7.71 kcal/mol, compound 17 (alpha-amyrine)-6.34 kcal/mol, and Finasteride-6.03 kcal/mol. Interestingly, the ΔG of compound 16 (olean-12-en-3beta-ol, cinnamate) is better than of minoxidil (-4.8 kcal/mol) and also to gold-standard treatment compound, finasteride. ADME-Tox prediction for compound 16 showed favorable results in several metrics such as skin permeability, absorption, and distribution. Compound 16 (olean-12-en-3beta-ol, cinnamate) is therefore a potential androgen receptor antagonist and may be beneficial in the treatment of alopecia.