Pharmaceutical Compounds Research Articles

Piracetam reduces oxidative stress and mitochondrial function impairment in an in vitro model of vascular dementia.

Vascular dementia (VaD) is the most common cause of dementia in older adults. Due to the lack of effective treatment options, there is an urgent need to find an effective pharmaceutical compound to combat VaD. Piracetam has been reported to improve impaired cognitive function in a variety of conditions in both human and animal models. However, the role and mechanism of Piracetam in VaD remain unclear. Therefore this study aimed to elucidate the effect of Piracetam on a cellular model of VaD in vitro. We found that Piracetam enhanced the growth of OGD-stimulated SH-SY5Y cells. In addition, Piracetam inhibited the oxidative stress of OGD-stimulated SH-SY5Y cells. Further, Piracetam improved mitochondrial function of OGD-stimulated SH-SY5Y cells. Mechanistically, Piracetam inhibited the PI3K/Akt/mTOR pathway in OGD-stimulated SH-SY5Y cells. Collectively, Piracetam improved oxidative stress and mitochondrial dysfunction of OGD-stimulated SH-SY5Y cells through PI3K/Akt/mTOR axis. Hence, Piracetam has the potential to serve as a promising drug of VaD.

High-efficiently utilizing micro-nano ozone bubbles to enhance electro-peroxone process for rapid removal of trace pharmaceutical contaminants from hospital wastewater

The electro-peroxone (EP) process encounters two inherent challenges in wastewater treatment: sluggish O2/O3 transfer and substantial ozone waste. To overcome these limitations, we introduced micro-nano bubbles (MNBs) aeration to enhance O2/O3 dissolution and diffusion, ultimately aiming to improve the removal of trace pharmaceutical contaminants from hospital wastewater. In the MNBs aeration system, the ozone transfer coefficient ranging from 0.536 to 0.265 min−1, significantly surpassing that of conventional aeration (0.220 to 0.090 min−1) by approximately 2 to 4.5 times. Consequently, the EP process under MNBs aeration significantly enhanced ozone-resistant ibuprofen (IBU) removal, achieving a removal rate of 98.4 ± 1.5 %, far exceeding the 47.3 ± 4.7 % observed with conventional aeration. This significant improvement was attributed to the heightened production of hydroxyl radicals (•OH), reaching 0.97 × 10−9 M s, compared to only 0.28 × 10−9 M s in conventional aeration. The mechanism behind the enhanced •OH production in the MNBs-EP process relied primarily on two factors: improved O2/O3 dissolution due to high internal pressure/large surface and enhanced O3/H2O2 activation from high collapse energy. These factors together contributed to the robust oxidation capability of the MNBs-EP system. As a result, over 97 % removal efficiency was achieved for five representative pharmaceutical pollutants (sulfamethoxazole, ribavirin, norfloxacin, tetracycline and ampicillin) in just 1 min. Furthermore, when applied to real hospital wastewater, the MNBs-O3-E treatment system reduced all 15 detected trace pharmaceutical compounds to below 10 ng L−1 and achieved 14 types of pollutants with removal rates of over 85 % within 15 min, resulting in an ultrahigh total removal rate of 98.6 %, from an initial total concentration of 2108 ng L−1 to less than 30 ng L−1. Thus, micro-nano aeration endowed the EP process as a promising advanced oxidation system for rapid and highly-effective removal of trace pharmaceutical contaminants from hospital wastewater.

Advancing thermal stability analysis of haloperidol: Integrative approaches and optimization strategies for enhanced pharmaceutical formulations

This study investigates the thermal stability of haloperidol, a crucial pharmaceutical compound, employing a multidimensional approach encompassing UV spectrometry, thermal degradation studies, kinetics analysis, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). The UV spectrometry method demonstrates exceptional linearity across a concentration range of 2–34 µg/ml, meeting stringent industry standards. Thermal degradation studies affirm the compound's stability when exposed to 80°C for 6 h. Kinetic analysis indicates a first-order reaction for the degradation process, with activation energy values suggesting a sluggish degradation profile under diverse heat stress conditions. FTIR analysis underscores the consistency of haloperidol's molecular structure across varying temperatures, while XRD confirms the retention of its crystalline form even under heat stress. DSC analysis unveils a melting temperature of 150°C, indicative of initial melting preceding degradation. Response surface methodology (RSM) optimization identifies the conservation conditions effects (temperature and time)to minimize degradation, a finding substantiated by predictions from the Improved Grey Wolf Optimization (IGWO) algorithm and subsequent experimental validation. Furthermore, a bespoke MATLAB application is developed to streamline and enhance the accuracy of the complex optimization processes. This tool offers advanced features for predicting and optimizing haloperidol degradation rates, catering to the needs of both researchers and industry professionals. In essence, this study not only sheds light on the thermal stability of haloperidol but also provides practical tools and insights crucial for optimizing its stability under diverse environmental conditions, thereby bolstering its pharmaceutical applicability and efficacy.

Targeting the Receptor Complexes by Structure-based Natural Drug Compounds in Seizures: A New Dimension in Drug Discovery and Design

Targeting the Receptor Complexes by Structure-based Natural Drug Compounds in Seizures: A New Dimension in Drug Discovery and Design

Synthesis of zero valent copper/iron nanoparticles using Piper betle leaves for the removal of pharmaceutical contaminant atorvastatin

In this study, bimetallic Cu–Fe nanoparticles were synthesized using the green approach with Piper betle leaves, and the removal efficiency of one of the pharmaceutical compounds, Atorvastatin, was investigated. UV, SEM, FTIR, EDAX, particle size, and zeta potential measurements were used to confirm nanoparticle fabrication. The removal efficiency of Atorvastatin (10 mg/L) by bimetallic Cu–Fe nanoparticles was 67% with a contact time of 30 min at pH 4, the adsorbent dosage of 0.2 g/L, and stirring at 100 rpm. Piper betle bimetallic Cu–Fe nanoparticles have demonstrated excellent stability, reusability, and durability, even after being reused five times. Furthermore, the synthesized bimetallic Cu–Fe nanoparticles demonstrated remarkable antimicrobial properties against gram-negative strains such as Escherichia coli and Klebsiella pneumoniae, gram-positive strains such as Staphylococcus aureus and Bacillus subtilis, and fungi such as Aspergillus niger. In addition, the antioxidant properties of the synthesized bimetallic Cu–Fe nanoparticles were assessed using the DPPH radical scavenging assay. The results indicated that the nanoparticles had good antioxidant activity. Thus, using Piper betle extract to make Cu–Fe nanoparticles made the procedure less expensive, chemical-free, and environmentally friendly, and the synthesized bimetallic Cu–Fe nanoparticles helped remove the pharmaceutical compound Atorvastatin from wastewater.

Genomic insights into an endophytic Streptomyces sp. VITGV156 for antimicrobial compounds.

Endophytic Streptomyces sp. are recognized as a potential resource for valuable natural products but are less explored. This study focused on exploring endophytic Streptomyces species residing within tomato plants (Solanum lycopersicum) harboring genes for the production of a novel class of antibiotics. Our research involved the isolation and characterization of Streptomyces sp. VITGV156, a newly identified endophytic Streptomyces species that produces antimicrobial products. VITGV156 harbors a genome of 8.18 mb and codes 6,512 proteins, of which 4,993 are of known function (76.67%) and 1,519 are of unknown function (23.32%). By employing genomic analysis, we elucidate the genome landscape of this microbial strain and shed light on various BGCs responsible for producing polyketide antimicrobial compounds, with particular emphasis on the antibiotic kendomycin. We extended our study by evaluating the antibacterial properties of kendomycin. Overall, this study provides valuable insights into the genome of endophytic Streptomyces species, particularly Streptomyces sp. VITGV156, which are prolific producers of antimicrobial agents. These findings hold promise for further research and exploitation of pharmaceutical compounds, offering opportunities for the development of novel antimicrobial drugs.

Magnetite nanoparticle mediated ozonation of ciprofloxacin wastewater: energy calculation and optimization of parameters

This study focuses on synthesizing a catalyst that can quickly degrade micropollutants in water with minimal ozone exposure. While ozone is an effective oxidizing agent, it can harm the environment at higher concentrations if released in gaseous form. Thus, due to their efficiency and non-toxicity, researchers prefer to use hydroxyl radicals as oxidizing agents. In this study, Fe magnetite nanoparticles (FeNPs) have been synthesized to generate hydroxyl radicals for ozonation. The stability and effectiveness of the FeNPs as an ozonation catalyst were tested under different pH levels and ozone doses. Promising results have been obtained showing complete degradation of the model pharmaceutical compound within 10 min for the catalytic ozonation process. The parameters have been optimized for the holistic picture of the process, and their significance on the % degradation has been evaluated thoroughly. The energy requirement of the process has been evaluated to compare the proposed work with the available AOPs. It was found that the heterogenous catalytic ozonation process projects a much lower energy requirement as compared to many other AOPs.

Aromatically different Apiaceae spices harbour potential novel antibacterial compounds for drug repurposing against ESKAPE pathogens

Aromatically different Apiaceae spices harbour potential novel antibacterial compounds for drug repurposing against ESKAPE pathogens

Spatial occurrence and variation of the active pharmaceutical compounds in rivers and groundwater systems in Arusha City, Tanzania

This study investigated the occurrence of 11 pharmaceutical compounds in the rivers and groundwater systems of Arusha City, Tanzania. Each suspected individual residue of active pharmaceutical compounds in water matrices, was pre-concentrated using solid-phase extraction techniques and, then quantified using a liquid chromatography-mass spectrometer mass spectrometer (LC-MS/MS). The concentrations varied across the assessed rivers and groundwater systems. High concentrations of caffeine 520 ng/L were detected in the station downwards of a wastewater stabilization pond, discharging its partially treated effluent into the river, followed by stations whose rivers flowed through informal areas. Sampled points' located near the river's water sources reported fewer compounds with values below the detection limit, such as amoxicillin, paracetamols, and doxycycline. Except for sulfamethoxazole (94 ng/L) in the borehole, most of the concentrations detected in rivers were ten times higher than in boreholes. In addition, in boreholes, more compounds were identified in the monitoring than in the domestic ones, and concentration varied with depth of deep boreholes (25 m) were less abundant than shallow wells of less than 10 m. In conclusion, pharmaceutical compounds were frequently detected in both rivers and groundwater systems within Arusha City suggesting the need for understanding of their fates and associated risks.

An Investigation into the Effects of Chemical, Pharmaceutical, and Herbal Compounds on Neuroglobin: A Literature Review.

Neuroglobin (Ngb) is an oxygen-binding globin protein that is mainly expressed in the neurons of the central and peripheral nervous system. However, moderate levels of Ngb have also been detected in non-neural tissues. Ngb and Ngb modulating factors have been increasingly studied over the last decade due to their neuroprotective role in neurological disorders and hypoxia. Studies have shown that a number of chemicals, pharmaceuticals, and herbal compounds can modulate the expression of Ngb at different dose levels, indicating a protective role against neurodegenerative diseases. Iron chelators, hormones, antidiabetic drugs, anticoagulants, antidepressants, plant derivatives and short-chain fatty acids are among these compounds. Therefore, this study aimed to review the literature focused on the possible effects and mechanisms of chemical, pharmaceutical, and herbal compounds on Ngbs.

Ciprofloxacin adsorption onto Pumice-bentonite composites: Modeling, kinetics, equilibriums and reusability studies

BackgroundA new Bentonite-loaded Pumice adsorbent (P-BNT3) was successfully synthesized as an efficient adsorbent for CIP removal from aqueous solutions. MethodsIn the present study, P-BNT3 composite synthesized by hydrothermal technique (24 h @160 °C) was loaded with Bentonite (BNT) using ultrasonication (20 min @25 °C) to remove CIP antibiotic. P-BNT3 composite was characterized by FTIR, XRD, BET, TGA, SEM, and TEM analyses. XRD, SEM, and TEM analyses indicate effective coupling of Pumice/ BNT strong layers with highly porous heterogeneous structure. Adsorption of CIP is studied as a function of pH, dosage, contact time, initial CIP concentration, and temperature in a batch reactor to obtain the maximum adsorption capacity (qm). Significant FindingsA MFSO kinetic model (R2= 0.983) and Langmuir and Dubinin–Radushkevich isotherm model (R2= 0.989 and 0.986) provide good fits to the experimental. The highest amount of CIP adsorbed is 54 mg/g at pH=2.0, which is 5 folds higher than pristine Pumice. The adsorption equilibrium was attained in 240 min with P-BNT3 for a CIP concentration of 30 mg/L. The characterization of spent composites after CIP adsorption suggested that CIP adsorption onto P-BNT3 composite is governed by π-π interaction, chemical complexation, and surface interactions. Based on thermodynamic investigation over the temperature range of 298 ̶ 318 K, CIP adsorption on P-BNT3 was a spontaneous (-ΔG°) and endothermic (ΔH°=+5.313) phenomenon. Furthermore, the adsorption-desorption procedure demonstrated that the composite could be efficiently reused up to 5 times. However, expensive desorption costs and the inevitable secondary effluent are a challenge in the practical implementation. Based on the findings, the P-BNT3 composite has great potential for the removal of other pharmaceutical compounds.

The Perpetual Impact of COVID-19 on the Geriatric Population's Quality of Life and Potential Preventive and Therapeutic Measures in Unani Medicine: An Evidence-based Review

Background: COVID-19 pandemic has affected the elderly population more severely than many other patient groups. Due to their constitutional weakness and co-morbidities, geriatric populations are more prone to complications and adverse outcomes, especially with a high viral load. The Unani system of medicine encompasses several guidelines for the prevention and treatment of epidemics, which are stratified for different types of people with respect to age, geography, and health status, among others. Objective: Since Unani drugs are both safe and efficient, it has been found that demand for them has surged since COVID. This paper aims to discuss the various immunomodulatory, longevity-promoting agents, and organ-specific tonics specified in Unani medicine for the care of the elderly, which may be helpful during epidemics, and also, to present the scientific evidence of their efficacy. Methods: A thorough assessment of the available literature was carried out utilizing several electronic databases, including PubMed, Science Direct, Web of Science, Wiley Online, Google Scholar, and Springer Link, using the terms "Geriatrics," "Elderly," "SARS-CoV-2," "Unani," and many others, up until October 2022. A total of 61 pertinent reviews were included. To gather information on epidemics and their specific response in geriatrics, monographs in Urdu, Arabic, and English were explored in addition to classic Unani texts such Al-Qanun fit Tibb (The Canon of Medicine), Kamil-us-Sana'at (Liber Regius), Kitab al-Hawi fit Tibb (Liber Continence), and others. Plant names were confirmed by “The Plant List” (www.theplantlist.org). Results: During pandemics, Unani medicine aims to promote and preserve the health of the elderly by regulating six important factors (Asbāb Sitta Ḍarūriyya), which include adopting a specific diet, regimen and drugs as effective prophylactic strategies. However, the role of Unani medicine in immunological regulation relies on major organ protection, viz., general body tonic, nervine tonic, heart tonic, and liver tonic. Several Unani single drugs, such as Sibr (Aloe barbadensis Mill.), Zafran (Crocus sativus L.), and Mur (Commiphora myrrh Nees.), and formulations, such as Khameera Marwareed, Tiryaq-i- Arba, and Habb-i- Jadawar have also been found to be very effective in validated scientific preclinical and clinical studies. Furthermore, Unani drugs have anti-inflammatory, analgesic, and tonic actions, contributing to their holistic efficacy. Conclusion: It is observed in this review that Unani medicine employs a holistic approach to the health protection of the elderly. There are various dietary recommendations, lifestyle modifications, regimental therapy, and pharmacotherapy prescribed as per the individual’s requirements and needs to reduce geriatric mortality in times of epidemics. Modern pharmacological studies have discovered many bioactive compounds in health-protective drugs prescribed in Unani medicine, such as Vitis vinifera L., Ziziphus jujube Mill., and many others, further substantiating the literature.

Red Sea Sponge Callyspongia siphonella Extract Induced Growth Inhibition and Apoptosis in Breast MCF-7 and Hepatic HepG-2 Cancer Cell Lines in 2D and 3D Cell Cultures.

The increasing incidence of cancer diseases necessitates the urgent exploration of new bioactive compounds. One of the trends in drug discovery is marine sponges which is gaining significant support due to the abundant production of natural pharmaceutical compounds obtained from marine ecosystems. This study evaluates the anticancer properties of an organic extract from the Red Sea sponge Callyspongia siphonella (C. siphonella) on HepG-2 and MCF-7 cancer cell lines. C. siphonella was collected, freeze-dried, and extracted using a methanol-dichloromethane mixture. The extract was analyzed via Liquid Chromatography-Mass Spectrometry. Cytotoxic effects were assessed through cell viability assays, apoptosis detection, cell cycle analysis, mitochondrial membrane potential assays, scratch-wound healing assays, and 3D cell culture assays. Fifteen compounds were identified in the C. siphonella extract. The extract showed moderate cytotoxicity against MCF-7 and HepG-2 cells, with IC50 values of 35.6 ± 6.9 μg/mL and 64.4 ± 8 μg/mL, respectively, after 48 hours of treatment. It induced cell cycle arrest at the G2/M phase in MCF-7 cells and the S phase in HepG-2 cells. Apoptosis increased significantly in both cell lines, accompanied by reduced mitochondrial membrane potential. The extract inhibited cell migration, with notable reductions after 24 and 48 hours. In 3D cell cultures, the extract had IC50 values of 5.1 ± 2 μg/mL for MCF-7 and 166.4 ± 27 μg/mL for HepG-2 after 7 days of treatment, showing greater potency in MCF-7 spheres compared to HepG-2 spheres. The anticancer activity is attributed to the bioactive compounds. The C. siphonella extract's ability to induce apoptosis, disrupt mitochondrial membrane potential, and arrest the cell cycle highlights its potential as a novel anticancer agent. Additional research is required to investigate the underlying mechanism by which this extract functions as a highly effective anticancer agent.

Electrochemical degradation of carbamazepine in water by a flow-through and pilot-scale reactor with carbon felt electrodes: Parametric study under realistic operational conditions

Carbamazepine (CBZ) is one of the most stable pharmaceutical compounds that is commonly found in the effluents of wastewater treatment plants (WWTP). In this context, this contribution presents a comprehensive analysis of the different operating parameters of a flow-through and pilot-scale cylindrical reactor for hydrogen peroxide (H2O2) generation, in which the degradation of CBZ takes place. The electrochemical system was evaluated using 8 L of electrolytes prepared with tap water in the presence of methanol as dissolved organic matter or spiked tertiary WWTP effluent, at a volumetric flow of 7 L min−1. This reactor (i) improves the mass transport due to its flow-through configuration using fibrous quasi-three-dimensional carbon felt electrodes, (ii) operates without an external oxygen supply to promote the H2O2 electrosynthesis because it is incorporated by a jet aerator (iii) achieves the Fenton reaction at circumneutral pH due to Fe(II) disposition from a cation exchange resin. At first, the carbonaceous materials were electrochemically characterized by cyclic voltammetry measurements. Different operating parameters were evaluated by factorial design methodologies for H2O2 generation, energetic consumption and CBZ removal. The application of a current density of 1.4 mA cm−2, in a cathode-anode-cathode arrangement immersed in a 120 mM ionic strength solution, allowed to obtain up to 6.4 mg H2O2 L−1 after 40 min, consuming 0.44 kWh m−3. Later, the Fenton reaction was validated by a florescence study, and by the incorporation of 0.75 g of granular activated carbon and 5 g of Fe(II) loaded resin, CBZ abatement yields of 68 % and 32 % were obtained using a synthetic solution and a spiked tertiary WWTP effluent, respectively, and up to 28 % of the dissolved total organic carbon was removed. Finally, an analysis of the stability of the carbon felt electrodes was tackled using scanning electron microscopy and energy-dispersive X-ray spectroscopy.

Hydrophilic Interaction Liquid Chromatography for the Analysis of Pharmaceutical Formulations

Abstract: For a long time, Reversed-Phase Liquid Chromatography (RPLC) was the most dominant technique for the analysis of pharmaceutical compounds, but with poor efficiency in the separation of small polar molecules. From the efforts to solve the problem of insufficient retention of these molecules, during the last decades, a mode of liquid chromatography named Hydrophilic Interaction Liquid Chromatography (HILIC) has experienced vast expansion. It is based on the use of a highly hydrophilic stationary phase along with an aqueous mobile phase with high organic modifier content. In this review, the characteristics of stationary and mobile phases used in HILIC are described, and corresponding separation mechanisms are discussed. An overview of recently published papers dealing with the application of HILIC in analyzing pharmaceuticals in biological and non-biological samples is provided. Besides, the application of HILIC systems in the determination of the physicochemical properties of compounds is described.

Mechanism of Dabugan Decoction in treatment of generalized anxiety disorder based on network pharmacology and experimental verification

This study aims to explore the mechanism of Dabugan Decoction in the treatment of generalized anxiety disorder(GAD) based on network pharmacology, molecular docking, and animal experiments. Network pharmacology and molecular docking technology were used to obtain the possible targets and related signaling pathways of Dabugan Decoction in the treatment of GAD. The GAD rat model was established, and the corresponding drugs were given by gavage after randomization. After 28 days of continuous intervention, the anxiety state of rats was detected, and the pathological changes of the hippocampus were detected in each group. ELISA and Western blot were used to detect the protein expression levels of related molecules. A total of 65 drug compounds in Dabugan Decoction were obtained, involving 403 targets of action, 7 398 disease targets of GAD, and 279 common targets of "drug-disease". The key nodes in the protein-protein interaction(PPI) network were Akt1, TNF, IL-6, TP53, IL-1β, etc. Function analysis of Gene Ontology(GO) and enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG) showed that the PI3K-Akt signaling pathway was the most important pathway. The results of molecular docking showed that the core components of the drug had good binding activity with the corresponding key targets. Animal experiments showed that Dabugan Decoction could effectively improve the anxiety behavior of rats and increase the open arm end movement distance and total distance of rats in the elevated cross labyrinth, the number and stay time of entering the open box, and the time(%) and the number of entering the center of the open field. At the same time, HE staining and Nicil staining showed that the number of hippocampal nerve cells in rats increased, and they were closely arranged. The damage to the cell body was improved, and there was an increase in Nissl substances in the cells. The expression of TNF-α, IL-6, and IL-1β in rat hippocampus decreased, and the expression of TP53, p-Akt1, and p-PI3K increased. The mechanism may be related to the activation of the PI3K-Akt signaling pathway and the inhibition of inflammatory response. Dabugan Decoction can play a good therapeutic and regulatory role in GAD, reflecting the overall effect of traditional Chinese medicine(TCM) compound and the characteristics of multiple targets and multiple pathways. At the same time, it is preliminarily discussed that the state of GAD may be improved by Dabugan Decoction via-activating PI3K-Akt signaling pathway and inhibiting inflammatory response and anti-apoptosis, thus providing experimental data support for the clinical application of Dabugan Decoction.

Biodegradation of Pharmaceutical Pollutants Using Fungal Enzyme

Abstract: The potential of filamentous fungi and their enzymes are investigated for bioremediating pharmaceutical pollutants from wastewater thereby addressing the growing concern of emerging pollutants in water resources. Among the various microorganisms, the current abstract discusses the role of fungi in degrading antibiotics and persistent pharmaceutical compounds. These fungi allow the biodegradation via the formation of highly oxidative hydroxyl radicals. It summarizes the role of both intra (cytochrome P450) and extracellular (laccase) enzyme systems for the bioremediation of emerging clinical pollutants. It emphasizes the importance of both biosorption and biodegradation for effective pollutant removal by breaking down pharmaceuticals (e.g. antibiotics) and other hazardous compounds (e.g. endocrine-disrupting compounds, polycyclic aromatic hydrocarbons). Although the enzymes CYP450 are not directly engaged, their metabolic pathways execute mechanisms such as oxidation, the formation of reactive intermediates, and chemical modification, all of which result in the degradation of clinical pollutants. Amongst all enzyme systems in the case of laccase which oxidise a wide spectrum of substrates, converts them to free radicals. Additionally, the role of recombinant enzyme production and transgenic strains for pollutant degradation has also been elaborated. These considerations emphasise the need for ongoing research and biotechnological advancements to address the growing concern of pharmaceuticals and personal care product pollutants in water systems.

Unveiling the dynamic and thermodynamic interactions of hydrocortisone with β-cyclodextrin and its methylated derivatives through insights from molecular dynamics simulations

Cyclodextrins (CDs) can enhance the stability and bioavailability of pharmaceutical compounds by encapsulating them within their cavities. This study utilized molecular dynamics simulations to investigate the interaction mechanisms between hydrocortisone (HC) and various methylated CD derivatives. The results reveal that the loading of HC into CD cavities follows different mechanisms depending on the degree and position of methylation. Loading into βCD and 6-MeβCD was more complete, with the hydroxyl groups of HC facing the primary hydroxyl rim (PHR) and the ketone side facing the secondary hydroxyl rim (SHR). In contrast, 2,3-D-MeβCD and 2,6-D-MeβCD showed a different loading mechanism, with the ketone side facing the PHR and the hydroxyl groups facing the SHR. The root mean square fluctuation (RMSF) analysis demonstrated that methylation increases the flexibility of CD heavy atoms, with 3-MeβCD and 2,3-D-MeβCD exhibiting the highest flexibility. However, upon inclusion of HC, 3-MeβCD, 2,3-D-MeβCD, 2-MeβCD, and 6-MeβCD showed a significant reduction in flexibility, suggesting a more rigid structure that effectively retains HC within their cavities. The radial distribution function revealed a significant reduction in the number of water molecules within the innermost layer of the methylated CD cavities, particularly in TMeβCD, indicating a decrease in polarity. The presence of HC led to the release of high-energy water molecules, creating more favorable conditions for HC loading. Conformational analysis showed that methylation caused a partial decrease in the area of the PHR, a significant decrease in the area of the middle rim, and a notable decrease in the area of the SHR. The loading of HC increased the area of the PHR in most derivatives, with the most pronounced increase observed in 2,6-D-MeβCD and 6-MeβCD. The analysis of interaction energies and binding free energies demonstrated that the binding of HC to methylated CD derivatives is thermodynamically more favorable than to βCD, with the strongest association observed for 6-MeβCD, 2-MeβCD, and 2,3-D-MeβCD.

Identification of therapeutic drug target of Shigella Flexneri serotype X through subtractive genomic approach and in-silico screening based on drug repurposing

Shigellosis, induced by Shigella flexneri, constitutes a significant health burden in developing nations, particularly impacting socioeconomically disadvantaged communities. Designated as the second most prevalent cause of diarrheal illness by the World Health Organization (WHO), it precipitates an estimated 212,000 fatalities annually. Within the spectrum of S. flexneri strains, serotype X is notably pervasive and resilient, yet its comprehensive characterization remains deficient. The present investigation endeavors to discern potential pharmacological targets and repurpose existing drug compounds against S. flexneri serotype X. Employing the framework of subtractive genomics, the study interrogates the reference genome of S. flexneri Serotype X (strain 2,002,017; UP000001884) to delineate its proteome into categories of non-homologous, non-paralogous, essential, virulent, and resistant constituents, thereby facilitating the identification of therapeutic targets. Subsequently, a screening of approximately 9000 compounds from the FDA library against the identified drug target aims to delineate efficacious agents for combating S. flexneri serotype X infections. The application of subtractive genomics methodology yields prognostic insights, unveiling non-paralogous proteins (n = 4122), non-homologues (n = 1803), essential (n = 1246), drug-like (n = 389), resistant (n = 167), alongside 42 virulent proteins within the reference proteome. This iterative process culminates in the identification of Serine O-acetyltransferase as a viable drug target. Subsequent virtual screening endeavors to unearth FDA-approved medicinal compounds capable of inhibiting Serine O-acetyltransferase. Noteworthy candidates such as DB12983, DB15085, DB16098, DB16185, and DB16262 emerge, exhibiting potential for mitigating S. flexneri Serotype X. Despite the auspicious findings, diligent scrutiny is imperative to ascertain the efficacy and safety profile of the proposed drug candidates vis-à-vis S. flexneri.

A Review on Artificial Intelligence in Pharmaceutical Science

Abstract: In recent years, the use of artificial intelligence (AI) in health care has risen steadily, including a wide range of applications in the field of pharmacology. AI is now used throughout the entire continuum of pharmacology research and clinical practice and from early drug discovery to real-world data mining. The types of AI models used range from unsupervised clustering of drugs or patients aimed at identifying potential drug compounds or suitable patient populations, to supervised machine learning approaches to improve therapeutic drug monitoring. Additionally, natural language processing is increasingly used to mine electronic health records to obtain real-world data. In this mini-review, we discuss the basics of AI followed by an outline of its application in pharmacology research and clinical practice. Artificial intelligence is the upcoming technology in advance health care system. Current digitalization of medicine and availability of electronic health records (EHRs) has inspired clinical researchers and healthcare personnel to acquire artificial intelligence (AI) methodologies for big data analytics and for very large scale medical databases. The major advantage of AI is that it reduces the time that is needed for drug development and, in turn, it reduces the costs that are associated with drug development, enhances the returns on investment and may even cause a decrease in cost for the end user. A large number of researches are being carried out to improve the current available AI technology to make the pharmacy profession more efficient. The present article briefly describes the importance of AI in the process of drug development and then looks at the various AI tools that are available at the disposal of a modern-day pharmacist to aid in a more efficient functioning.