Revolutionizing Diabetes Care: The Role of Marine Bioactive Compounds and Microorganisms.

Diabetes is a metabolic condition characterized by high blood glucose levels. Aquatic products like microalgae, bacteria, seagrasses, macroalgae, corals, and sponges have been investigated for potential anti-diabetic properties. We looked at polyphenols, peptides, pigments, and sterols, as well as other bioactive substances found in marine resources, to see if they could help treat or manage diabetes, in addition to describing the several treatment strategies that alter diabetes and its implications, such as inhibition of protein tyrosine phosphatases 1B (PTP1B), α-glucosidase, α-amylase, dipeptidyl peptidase IV (DPP-IV), aldose reductase, lipase, glycogen synthase kinase 3ß (GSK-3ß), and insulin resistance prevention, promotion of liver antioxidant capacity, natural killer cell stimulant, anti-inflammatory actions, increased AMP-activated protein kinase (AMPK) phosphorylation and sugar and metabolism of the lipid, reducing oxidative stress, and ß-pancreatic cell prevention. This study highlights the revolutionary potential of marine bioactive compounds and microorganisms in transforming diabetes care. We believe in a future in which innovative, sustainable, and efficient therapeutic approaches will result in improved quality of life and better outcomes for people with diabetes mellitus by forging a new path for treatment, utilizing the power of the world's oceans, and capitalizing on the symbiotic relationship between humans and the marine ecosystem. This study area offers optimism and promising opportunities for transforming diabetes care.

Assessment of the Water Sorption Capacity of Rifaximin Using the Dynamic Vapor Sorption Technique for Optimization of the Choice of Excipients and the Manufacturing Environment of Rifaximin Tablets.

BACKGROUND: Rifaximin, a medication of the rifamycin family with two distinct strengths of 200 mg and 550 mg in tablet form, is useful for the treatment of travelers' diarrhea. It has a solid yellow hue and is very hygroscopic in nature. It exhibits a variety of polymorphic forms such as α, ß, γ, δ, and ε depending on bonded moisture. These polymorphs' varying chemical and physical characteristics, such as solubility and water content, may have a big impact on in vivo absorption, which in turn affects efficacy and safety. Therefore, understanding the polymorphic stability of rifaximin is crucial for formulating rifaximin tablets. OBJECTIVE: The current effort focuses on the understanding of water vapor sorption properties to control the polymorphic stability of rifaximin in the tablet formulation using the appropriate selection of excipients and manufacturing process. METHODS: The dynamic vapor sorption method in the range of 0-90% relative humidity at 25°C is used for understanding the sorption properties of drug substances and drug excipient mixtures; the state-of-the-art techniques of the X-ray diffraction method are used to identify polymorph conversions; and dissolution procedures are used for in vitro correlation studies. RESULTS: The sorption study data reveals that rifaximin is highly unstable at relative humidity conditions above 36%. When using excipients that have a low tendency to adsorb water in the formulation, the polymorphic results do not show any change in their intended form, and the in vitro dissolution data show an equivalency with the reference drug product. CONCLUSION: The study prompted a successful outcome-oriented development of the formulation processing environment conditions design to develop a test formulation that has adequate polymorphic stability and also similarity in in-vitro dissolution profiles, with the reference product with highest similarity. HIGHLIGHTS: The overall study described here is useful for swiftly gaining insight into the sorption characteristics of rifaximin, and it contributes to the widespread acceptance of rifaximin tablets as a treatment option.

Structural Elucidation of Novel Degradation Impurity and Development, Validation of a Single HPLC Method for all Putative Impurities of Clobetasol Propionate in a Foam Drug Product.

Clobetasol Propionate is a highly strong corticosteroid that is used in a variety of topical medication formulations, including foam, ointment, lotion, spray and shampoo; with a dosage strength of 0.05% (w/w). The goal of this research was to identify and characterize a substantial unknown impurity (UK) detected during the stability testing of a Clobetasol Propionate foam pharmaceutical product in accelerated conditions (40°C and 75% relative humidity). Developing a single, robust and accurate HPLC method that is LC-MS compatible for quantifying all 14 potential Clobetasol Propionate impurities in therapeutic drugs is another goal. Preparative column chromatography was used to separate the impurity, and spectroscopic techniques like IR, NMR and MS were used to characterize its structure. The structure of isolated UK was effectively characterized and defined using spectroscopic data evaluation. The chromatographic method has also been validated according to the International Conference on Hominization's Q (2) quality guidelines. The isolated and characterized impurity had the same equivalence as the impurity found during stability testing. Precision, accuracy, linearity, robustness and ruggedness are all met in the method validation data.

Systematic Selection of Impurities, Development, and Validation of Related Substance Methods for Estradiol and Progesterone in a Combination Drug Product.

BACKGROUND: A kind of estrogen called estradiol is a female sex hormone that regulates several body processes. In hormone replacement therapy for women, the endogenous steroid progesterone is employed. The soft gel capsule medication, which contains a mix of 1 mg estradiol and 100 mg progesterone, is used to treat moderate to severe menopause symptoms, such as hot flashes, in women who have uteruses, as well as feelings of warmth in the face, neck, and chest. OBJECTIVE: To establish the stability of drug products in accordance with the ICH Harmonized Tripartite Guideline, Stability Testing of New Drug Substances and Products (Q1A), this study aims to develop a reverse-phase chromatographic method, the necessary analytical methodology for identifying the drug degradation profiles. METHOD: The procedures were optimized using a C18 column (250 × 4.6 mm, 5 µ) as the stationary phase and conventional solvents such as water-acetonitrile mixtures as the mobile phase. A quantification technique had been an HPLC combined with a UV/PDA and fluorescence detector. RESULTS: The developed methods for both estradiol and progesterone were capable of all components of each active individually by overcoming the extremely difficult challenges of a combination product with similar structural compounds, having 24 impurities in all, and having complex excipients used for soft gel formulation. CONCLUSIONS: The method has been successfully created, validated for use in compliance with regulatory specifications, and determined to be accurate, linear, specific, and stability-indicating in nature. HIGHLIGHTS: To quantify the associated impurities of both actives in the presence of a highly complex matrix, the performance of the HPLC approach considerably possesses a higher degree of selectivity.

Investigational Study of DASATINIB N-Oxide Impurity in Different Diluents.

Dasatinib is an aminopyrimidine used as an inhibitor of multiple tyrosine kinases in two different formulations an immediate-release tablet and a powder for oral suspension. It shows a very low pH-dependent solubility in aqueous solutions and higher solubility in organic solvents. The solubility plays an essential role in analytical methodology to establish the purity, potency, safety and efficacy of any drug product as a diluent. Also, extraction of active drug substance with a suitable diluent from matrix composition is crucial for any analytical method development. However, a diluent optimization study during the method development of related substances for the drug product reveals that the Piperazine ring presented in Dasatinib is susceptible to oxidation and forms an N-oxide impurity. The impurity formation is due to the micro oxidic properties of the solvent used as a diluent which is inducing an oxidation reaction. Therefore, a comprehensive investigative study was conducted to optimize the diluent by limiting N-Oxide generation.

Synthesis of molnupiravir (MK-4482, EIDD-2801): a promising oral drug for the treatment of COVID-19 starting from cytidine.

The present work describes the synthesis of molnupiravir by employing commercially available inexpensive materials in two steps with an overall yield of 85.7%. The synthetic methodology starts with an eco-friendly starting material, that is, cytidine and establishes an alternative way to avoid costly enzyme mediated reactions. This synthetic strategy involves a selective acylation of cytidine as the first key step followed by the second step, that is, hydroxamination reaction. The major advantage of this protocol is that it is completely free of protection and deprotection reactions. Chemoselective acylation of cytidine's primary alcohol was achieved using isobutyryl chloride, Et3N, and DMF solvent (89.3% yield). The aqueous phase transformation was achieved for the hydroxamination reaction with a 96% yield.

Ultrasound assisted synthesis of 3-alkynyl substituted 2-chloroquinoxaline derivatives: Their in silico assessment as potential ligands for N-protein of SARS-CoV-2.

In view of recent global pandemic the 3-alkynyl substituted 2-chloroquinoxaline framework has been explored as a potential template for the design of molecules targeting COVID-19. Initial in silico studies of representative compounds to assess their binding affinities via docking into the N-terminal RNA-binding domain (NTD) of N-protein of SARS-CoV-2 prompted further study of these molecules. Thus building of a small library of molecules based on the said template became essential for this purpose. Accordingly, a convenient and environmentally safer method has been developed for the rapid synthesis of 3-alkynyl substituted 2-chloroquinoxaline derivatives under Cu-catalysis assisted by ultrasound. This simple and straightforward method involved the coupling of 2,3-dichloroquinoxaline with commercially available terminal alkynes in the presence of CuI, PPh3 and K2CO3 in PEG-400. Further in silico studies revealed some remarkable observations and established a virtual SAR (Structure Activity Relationship) within the series. Three compounds appeared as potential agents for further studies.

Ultrasound Assisted Synthesis of 2-Substituted Benzofurans via One-Pot and Sequential Method: Their In Vitro Evaluation.

BACKGROUND: The 2-substituted benzofuran framework has attracted enormous attention due to its presence in a range of bioactive compounds and natural products. While various methods for the synthesis of 2- substituted benzofuran derivatives are known, several of them suffer from certain drawbacks. OBJECTIVE: The main objective of this work was to explore a series of 2-(het)aryl substituted benzofurans derivatives for their cytotoxic properties against cancer cell lines in vitro. METHODS: In our efforts, we have developed a one-pot synthesis of this class of compounds via sequential C-C coupling followed by C-Si bond cleavage and subsequent tandem C-C/C-O bond-forming reaction under ultrasound irradiation. The methodology involved coupling of (trimethylsilyl)acetylene with iodoarenes in the presence of 10% Pd/C-CuI-PPh3-Et3N in MeOH followed by treating the reaction mixture with K2CO3 in aqueous MeOH and finally coupling with 2-iodophenol. A variety of 2-substituted benzofurans were synthesized using this methodology in good yield. All the synthesized compounds were tested in vitro against two cancer cell lines, e.g. MDAMB-231 and MCF-7 cell lines subsequently against SIRT1. RESULTS: The benzofuran derivative 3m showed encouraging growth inhibition of both MDAMB-231 and MCF- 7 cell lines and significant inhibition of SIRT1. The compound 3m also showed a concentration-dependent increase in the acetylation of p53. CONCLUSION: Our efforts not only accomplished a one-pot and direct access to 2-(het)aryl substituted benzofurans but also revealed that the benzofuran framework presented here could be a potential template for the identification of potent inhibitors of SIRT1.

Total Phenolic Content and Antioxidant Activity of Morinda tinctoria Leaves.

The antioxidant activity and total phenolic content of Morinda tinctoria leaves was evaluated. The successively extracted leaves of Morinda tinctoria using various solvents was analyzed for their total phenolic content. The extracts were subjected to column chromatography for the isolation of bioactive molecules. In vitro antioxidant activity was evaluated by employing different assays, including 2,2-diphenyl-1-picrylhydrazyl, nitric oxide scavenging assay and phosphomolybdenum reducing power assay. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging efficacy of hexane extract is significant at higher concentration (500 µg/ml-91.2±0.05%) and the efficacy at lower concentration is more significant for ethyl acetate extract (100 µg/ml - 65.1±0.05%). The total phenolic content was highest in methanol extract (5.30±0.011 µg/mg). Cynarin, a hydroxy cinnamic acid was isolated from chloroform extract; oleuropein, a polyphenolic iridoid was isolated from methanol extract. The results obtained suggeted that Morinda tinctoria leaf extracts possessed antioxidant properties and might offer protection from free radicals. Two compounds, cynarin and oleuropein were reported for the first time from Morinda tinctoria leaves.