Combating Parkinson's disease with plant-derived polyphenols: Targeting oxidative stress and neuroinflammation.

Parkinson's disease (PD) is a devastating neurodegenerative disorder predominantly affecting the elderly, characterized by the loss of dopaminergic neurons in the substantia nigra. Reactive oxygen species (ROS) generation plays a central role in the pathogenesis of PD and other neurodegenerative diseases. An imbalance between cellular antioxidant activity and ROS production leads to oxidative stress, contributing to disease progression. Dopamine metabolism, mitochondrial dysfunction, and neuroinflammation in dopaminergic neurons have been implicated in the pathogenesis of Parkinson's disease. Consequently, there is a pressing need for therapeutic interventions capable of scavenging ROS. Current pharmacological approaches, such as L-dihydroxyphenylalanine (levodopa or L-DOPA) and other drugs, provide symptomatic relief but are limited by severe side effects. Researchers worldwide have been exploring alternative compounds with less toxicity to address the multifaceted challenges associated with Parkinson's disease. In recent years, plant-derived polyphenolic compounds have gained significant attention as potential therapeutic agents. These compounds exhibit neuroprotective effects by targeting pathophysiological responses, including oxidative stress and neuroinflammation, in Parkinson's disease. The objective of this review is to summarize the current understanding of the neuroprotective effects of various polyphenols in Parkinson's disease, focusing on their antioxidant and anti-inflammatory properties, and to discuss their potential as therapeutic candidates. This review highlights the progress made in elucidating the molecular mechanisms of action of these polyphenols, identifying potential therapeutic targets, and optimizing their delivery and bioavailability. Well-designed clinical trials are necessary to establish the efficacy and safety of polyphenol-based interventions in the management of Parkinson's disease.

Biogenic silver nanoparticle synthesis using orange peel extract and its multifaceted biomedical application.

The aim of this study was to employ an agro-industrial byproduct, specifically Citrus sinensis peels, as a reservoir of polyphenols. The natural chemicals present in C. sinensis peels serve as reducing agents in an environmentally benign method for synthesizing silver nanoparticles (AgNPs). This methodology not only provides a more environmentally friendly method for synthesizing nanoparticles but also enhances the value of agricultural waste, emphasizing the sustainable utilization of resources. In our study, AgNPs were successfully synthesized using peel aqueous exact of C. sinensis and then their various biological activity has been investigated. The synthesized AgNPs were characterized by UV-vis spectroscopy, dynamic light scattering (DLS), scanning electron microscopy (SEM), energy-dispersive X-ray (EDX), and transmission electron microscopy (TEM) analysis. Furthermore, their effectiveness in inhibiting growth and biofilm formation of Escherichia coli, Staphylococcus aureus, and Candida albicans has been investigated. The minimum inhibitory concentrations (MIC) for E. coli and S. aureus were both 32 µg/mL, and for C. albicans, it was 128 µg/mL. At 250 µg/mL of AgNPs, 94% and 92% biofilm inhibition were observed against E. coli and S. aureus, respectively. Furthermore, AgNPs demonstrated significant toxic effects against human prostate cancer cell line DU145 as investigated by anti-apoptotic, 4',6-diamidino-2-phenylindole (DAPI), reactive oxygen species (ROS), and acridine orange/ethidium bromide (AO/EtBr) assays. We also conducted uptake analysis on these pathogens and cancer cell lines to preliminarily investigate the mechanisms underlying their toxic effects. These findings confirm that AgNPs can serve as a cost-effective, non-toxic, and environmentally friendly resource for green synthesis of medicinal AgNPs. Moreover, this approach offers an alternative recycling strategy that contributes to the sustainable use of biological by-products.

Unravelling the in vivo dynamics of liposomes: Insights into biodistribution and cellular membrane interactions.

Liposomes, as a colloidal drug delivery system dating back to the 1960s, remain a focal point of extensive research and stand as a highly efficient drug delivery method. The amalgamation of technological and biological advancements has propelled their evolution, elevating them to their current status. The key attributes of biodegradability and biocompatibility have been instrumental in driving substantial progress in liposome development. Demonstrating a remarkable ability to surmount barriers in drug absorption, enhance stability, and achieve targeted distribution within the body, liposomes have become pivotal in pharmaceutical research. In this comprehensive review, we delve into the intricate details of liposomal drug delivery systems, focusing specifically on their pharmacokinetics and cell membrane interactions via fusion, lipid exchange, endocytosis etc. Emphasizing the nuanced impact of various liposomal characteristics, we explore factors such as lipid composition, particle size, surface modifications, charge, dosage, and administration routes. By dissecting the multifaceted interactions between liposomes and biological barriers, including the reticuloendothelial system (RES), opsonization, enhanced permeability and retention (EPR) effect, ATP-binding cassette (ABC) phenomenon, and Complement Activation-Related Pseudoallergy (CARPA) effect, we provide a deeper understanding of liposomal behaviour in vivo. Furthermore, this review addresses the intricate challenges associated with translating liposomal technology into practical applications, offering insights into overcoming these hurdles. Additionally, we provide a comprehensive analysis of the clinical adoption and patent landscape of liposomes across diverse biomedical domains, shedding light on their potential implications for future research and therapeutic developments.

Anticancer potential of novel symmetrical and asymmetrical dihydropyridines against breast cancer via EGFR inhibition: molecular design, synthesis, analysis and screening.

A series of novel symmetrical and asymmetrical dihydropyridines (HD 1-15) were designed, subjected to in silico ADMET prediction, synthesized, analyzed by IR, NMR, Mass analytical techniques and evaluated against epidermal growth factor receptor (EGFR) as inhibitors against Breast cancer. The results of predicted ADMET studies demonstrated the drug-likeness properties of the reported compounds. The in vitro cytotoxicity assessment of the synthesized compounds revealed that all of them showed good activity (IC50 ranging from 16.75 to 66.54 µM) towards MCF-7 breast cancer cells compared to the standard drug, Lapatinib (IC50 = 2.02 µM). Among these, compounds HD-6, HD-7, and HD-8 displayed the most potent activity with IC50 value of 21.26, 16.75, and 18.33 µM, respectively. Cytotoxicity of all compounds was tested on normal vero cells for comparison at different concentrations using the MTT assay. In addition to the MTT assay, the potent dihydropyridines derivatives were screened for EGFRwt kinase inhibition assay at concentrations ranging from 1 nM to 360 nM. Among the three compounds tested, HD-8 showed reasonably good inhibition with an IC50 value of 15.90 ± 1.20 nM compared to a standard Lapatinib IC50 value of 10.28 ± 1.01 nM. Based on the molecular docking study against EGFR, the most active derivatives HD-7 and HD-8 were docked against the active site of the protein and showed better binding affinity than the standard lapatinib. Additionally, molecular dynamics (MD) simulations were performed to explore the stability of the protein-ligand complex, its dynamic behavior, and the binding affinity.

Pharmacokinetics and Pharmacodynamics of a Nanostructured Lipid Carrier Co-Encapsulating Artemether and miRNA for Mitigating Cerebral Malaria.

Cerebral malaria (CM), a severe neurological pathology caused by Plasmodium falciparum infection, poses a significant global health threat and has a high mortality rate. Conventional therapeutics cannot cross the blood-brain barrier (BBB) efficiently. Therefore, finding effective treatments remains challenging. The novelty of the treatment proposed in this study lies in the feasibility of intranasal (IN) delivery of the nanostructured lipid carrier system (NLC) combining microRNA (miRNA) and artemether (ARM) to enhance bioavailability and brain targeting. The rational use of NLCs and RNA-targeted therapeutics could revolutionize the treatment strategies for CM management. This study can potentially address the challenges in treating CM, allowing drugs to pass through the BBB. The NLC formulation was developed by a hot-melt homogenization process utilizing 3% (w/w) precirol and 1.5% (w/v) labrasol, resulting in particles with a size of 94.39 nm. This indicates an effective delivery to the brain via IN administration. The results further suggest the effective intracellular delivery of encapsulated miRNAs in the NLCs. Investigations with an experimental cerebral malaria mouse model showed a reduction in parasitaemia, preservation of BBB integrity, and reduced cerebral haemorrhages with the ARM+ miRNA-NLC treatment. Additionally, molecular discoveries revealed that nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and Interleukin-6 (IL-6) levels were reduced in the treated groups in comparison to the CM group. These results support the use of nanocarriers for IN administration, offering a viable method for mitigating CM through the increased bioavailability of therapeutics. Our findings have far-reaching implications for future research and personalized therapy.

Drug eluting protein and polysaccharides-based biofunctionalized fabric textiles- pioneering a new frontier in tissue engineering: An extensive review.

In the ever-evolving landscape of tissue engineering, medicated biotextiles have emerged as a game-changer. These remarkable textiles have garnered significant attention for their ability to craft tissue scaffolds that closely mimic the properties of natural tissues. This comprehensive review delves into the realm of medicated protein and polysaccharide-based biotextiles, exploring a diverse array of fabric materials. We unravel the intricate web of fabrication methods, ranging from weft/warp knitting to plain/stain weaving and braiding, each lending its unique touch to the world of biotextiles creation. Fibre production techniques, such as melt spinning, wet/gel spinning, and multicomponent spinning, are demystified to shed light on the magic behind these ground-breaking textiles. The biotextiles thus crafted exhibit exceptional physical and chemical properties that hold immense promise in the field of tissue engineering (TE). Our review underscores the myriad applications of drug-eluting protein and polysaccharide-based textiles, including TE, tissue repair, regeneration, and wound healing. Additionally, we delve into commercially available products that harness the potential of medicated biotextiles, paving the way for a brighter future in healthcare and regenerative medicine. Step into the world of innovation with medicated biotextiles-where science meets the art of healing.

Predictive insights into plant-based compounds as fibroblast growth factor receptor 1 inhibitors: a combined molecular docking and dynamics simulation study.

The discovery of novel therapeutic agents with potent anticancer activity remains a critical challenge in drug development. Natural products, particularly bioactive phytoconstituents derived from plants, have emerged as promising sources for anticancer drug discovery. In this study, we used virtual screening techniques to explore the potential of bioactive phytoconstituents as inhibitors of fibroblast growth factor receptor 1 (FGFR1), a key signaling protein implicated in cancer progression. We used virtual screening techniques to analyze phytoconstituents extracted from the IMPPAT 2.0 database. Our primary objective was to discover promising inhibitors of FGFR1. To ensure the selection of promising candidates, we initially filtered the molecules based on their physicochemical properties. Subsequently, we performed binding affinity calculations, PAINS, ADMET, and PASS filters to identify nontoxic and highly effective hits. Through this screening process, one phytocompound, namely Mundulone, emerged as a potential lead. This compound demonstrated an appreciable affinity for FGFR1 and exhibited specific interactions with the ATP-binding site residues. To gain further insights into the conformational dynamics of Mundulone and the reference FGFR1 inhibitor, Lenvatinib, we conducted time-evolution analyses employing 200 ns molecular dynamics simulations (MDS) and essential dynamics. These analyses provided valuable information regarding the dynamic behavior and stability of the compounds in complexes with FGFR1. Overall, the findings indicate that Mundulone exhibits promising binding affinity, specific interactions, and favorable drug profiles, making it a promising lead candidate. Further experimental analysis will be necessary to confirm its effectiveness and safety profiles for therapeutic advancement in the cancer field.Communicated by Ramaswamy H. Sarma.

Pioneering a paradigm shift in tissue engineering and regeneration with polysaccharides and proteins-based scaffolds: A comprehensive review.

In the realm of modern medicine, tissue engineering and regeneration stands as a beacon of hope, offering the promise of restoring form and function to damaged or diseased organs and tissues. Central to this revolutionary field are biological macromolecules-nature's own blueprints for regeneration. The growing interest in bio-derived macromolecules and their composites is driven by their environmentally friendly qualities, renewable nature, minimal carbon footprint, and widespread availability in our ecosystem. Capitalizing on these unique attributes, specific composites can be tailored and enhanced for potential utilization in the realm of tissue engineering (TE). This review predominantly concentrates on the present research trends involving TE scaffolds constructed from polysaccharides, proteins and glycosaminoglycans. It provides an overview of the prerequisites, production methods, and TE applications associated with a range of biological macromolecules. Furthermore, it tackles the challenges and opportunities arising from the adoption of these biomaterials in the field of TE. This review also presents a novel perspective on the development of functional biomaterials with broad applicability across various biomedical applications.

Unveiling the impact of aging on BBB and Alzheimer's disease: Factors and therapeutic implications.

Alzheimer's disease (AD) is a highly prevalent neurodegenerative condition that has devastating effects on individuals, often resulting in dementia. AD is primarily defined by the presence of extracellular plaques containing insoluble ß-amyloid peptide (Aß) and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein (P-tau). In addition, individuals afflicted by these age-related illnesses experience a diminished state of health, which places significant financial strain on their loved ones. Several risk factors play a significant role in the development of AD. These factors include genetics, diet, smoking, certain diseases (such as cerebrovascular diseases, obesity, hypertension, and dyslipidemia), age, and alcohol consumption. Age-related factors are key contributors to the development of vascular-based neurodegenerative diseases such as AD. In general, the process of aging can lead to changes in the immune system's responses and can also initiate inflammation in the brain. The chronic inflammation and the inflammatory mediators found in the brain play a crucial role in the dysfunction of the blood-brain barrier (BBB). Furthermore, maintaining BBB integrity is of utmost importance in preventing a wide range of neurological disorders. Therefore, in this review, we discussed the role of age and its related factors in the breakdown of the blood-brain barrier and the development of AD. We also discussed the importance of different compounds, such as those with anti-aging properties, and other compounds that can help maintain the integrity of the blood-brain barrier in the prevention of AD. This review builds a strong correlation between age-related factors, degradation of the BBB, and its impact on AD.

Traditional Uses, Phytochemistry, and Pharmacological Activities of Coleus amboinicus: A Comprehensive Review.

Coleus amboinicus Benth., also known as Plectranthus amboinicus (Lour.) Spreng., is a perennial plant from the Lamiaceae family commonly found in tropical and warm regions of Africa, Asia, and Australia. Folk medicine commonly employs this remedy to address various ailments, including but not limited to asthma, headaches, skin disorders, coughs, constipation, colds, and fevers. Several phytoconstituents from various phytochemical classes, such as phenolics, terpenoids, phenolic acids, flavonoids, flavones, and tannins, have been identified in Coleus amboinicus up to the present time. Numerous pharmacological properties of Coleus amboinicus crude extracts have been documented through both in vitro and in vivo studies, including but not limited to antitumor, antibacterial, antifungal, antiprotozoal, anti-inflammatory, antioxidant, antidiabetic, wound healing, analgesic, antirheumatic, and various other therapeutic effects. Due to its extensive history of traditional usage, the diverse array of bioactive phytochemicals, and numerous established pharmacological activities, Coleus amboinicus is widely regarded as having significant potential for clinical applications and warrants further exploration, development, and exploitation through research. With this context, the present study gathers information on the occurrence, biological description, cultivation, and nutritional values of Coleus amboinicus. Furthermore, it thoroughly discusses various phytoconstituents, along with their classes, present in Coleus amboinicus, followed by detailed descriptions of their pharmacological activities based on recent literature.

Synthesis, characterization and NLO properties of 1,4-phenylenediamine-based Schiff bases: a combined theoretical and experimental approach.

In the current study, three novel 1,4-phenylenediamine-based chromophores (3a-3c) were synthesized and characterized and then their nonlinear optical (NLO) characteristics were explored theoretically. The characterization was done by spectroscopic analysis, i.e. FT-IR, UV-Visible, and NMR spectroscopy, and elemental analysis. Notably, these chromophores exhibited UV-Visible absorption within the range of 378.635-384.757 nm in acetonitrile solvent. Additionally, the FMO findings for 3a-3c revealed the narrowest band gap (4.129 eV) for 3c. The GRPs for these chromophores were derived from HOMO-LUMO energy values, which showed correspondence with FMO results by depicting a minimum hardness (2.065 eV) for 3c. Among these compounds, 3c displayed the highest nonlinear behavior with maximum µtot, ßtot and γtot values of 4.79 D, 8.00 × 10-30 and 8.13 × 10-34 a.u., respectively. Our findings disclosed that the synthesized 1,4-phenylenediamine chromophores may be considered promising candidates for nonlinear optical materials, showing potential applications in the realm of optoelectronic devices.

Green Synthesis of Cerium Oxide Nanoparticles, Characterization, and Their Neuroprotective Effect on Hydrogen Peroxide-Induced Oxidative Injury in Human Neuroblastoma (SH-SY5Y) Cell Line.

Cerium oxide nanoparticles (CeO2NPs) have a broad scale of applications in the biomedical field due to their excellent physicochemical and catalytic properties. The present study aims to synthesize the CeO2NPs from Centella asiatica (C. asiatica) leaf extract, which has been used in Indian traditional medicine for its neuroprotective properties. The CeO2NPs were characterized by ultraviolet-visible, X-ray diffraction, Fourier transform infrared, Raman spectroscopy, scanning electron microscopy- energy dispersive X-ray spectroscopy, and high-resolution transmission electron microscopy. The antioxidant property was evaluated by 2,2-di (4-tert-octyl phenyl)-1-picrylhydrazyl and OH radical assays. The neuroprotective potential was assessed against the oxidative stress (OS) induced by H2O2 in the human neuroblastoma (SH-SY5Y) cell line. CeO2NPs exhibited significant DPPH and OH radical scavenging activity. Our results revealed that CeO2NPs significantly increased H2O2-induced cell viability, decreased lactate dehydrogenase, protein carbonyls, reactive oxygen species generation, apoptosis, and upregulated antioxidant enzyme activity. Our findings suggest that the CeO2NPs protect the SH-SY5Y cells from OS and apoptosis, which could potentially counter OS-related neurodegenerative disorders.

Bitter yet beneficial: The dual role of dietary alkaloids in managing diabetes and enhancing cognitive function.

With the rising prevalence of diabetes and its association with cognitive impairment, interest in the use of dietary alkaloids and other natural products has grown significantly. Understanding how these compounds manage diabetic cognitive dysfunction (DCD) is crucial. This comprehensive review explores the etiology of DCD and the effects of alkaloids in foods and dietary supplements that have been investigated as DCD therapies. Data on how dietary alkaloids like berberine, trigonelline, caffeine, capsaicin, 1-deoxynojirimycin, nuciferine, neferine, aegeline, tetramethylpyrazine, piperine, and others regulate cognition in diabetic disorders were collected from PubMed, Research Gate, Web of Science, Science Direct, and other relevant databases. Dietary alkaloids could improve memory in behavioral models and modulate the mechanisms underlying the cognitive benefits of these compounds, including their effects on glucose metabolism, gut microbiota, vasculopathy, neuroinflammation, and oxidative stress. Evidence suggests that dietary alkaloids hold promise for improving cognition in diabetic patients and could open exciting avenues for future research in diabetes management.

Nanozymes and carbon-dots based nanoplatforms for cancer imaging, diagnosis and therapeutics: Current trends and challenges.

Cancer patients face a significant clinical and socio-economic burden due to increased incidence, mortality, and poor survival. Factors like late diagnosis, recurrence, drug resistance, severe side effects, and poor bioavailability limit the scope of current therapies. There is a need for novel, cost-effective, and safe diagnostic methods, therapeutics to overcome recurrence and drug resistance, and drug delivery vehicles with enhanced bioavailability and less off-site toxicity. Advanced nanomaterial-based research is aiding cancer biologists by providing solutions for issues like hypoxia, tumor microenvironment, low stability, poor penetration, target non-specificity, and rapid drug clearance. Currently, nanozymes and carbon-dots are attractive due to their low cost, high catalytic activity, biocompatibility, and lower toxicity. Nanozymes and carbon-dots are increasingly used in imaging, biosensing, diagnosis, and targeted cancer therapy. Integrating these materials with advanced diagnostic tools like CT scans and MRIs can aid in clinical decision-making and enhance the effectiveness of chemotherapy, photothermal, photodynamic, and sonodynamic therapies, with minimal invasion and reduced collateral effects.

Identification of potential inhibitors targeting Ebola virus VP35 protein: a computational strategy.

Ebola virus (EBOV) poses a severe threat as a highly infectious pathogen, causing devastating hemorrhagic fever in both humans and animals. The EBOV virus VP35 protein plays a crucial role in viral replication and exhibits the ability to suppress the host interferon cascade, leading to immune system depletion. As a potential drug target, VP35 protein inhibition holds promise for combating EBOV. To discover new drug candidates, we employed a computer-aided drug design approach, focusing on compounds capable of inhibiting VP35 protein replication. In this connection, a pharmacophore model was generated using molecular interactions between the VP35 protein and its inhibitor. ZINC and Cambridge database were screened using validated pharmacophore model. Further the compounds were filtered based on Lipinski's rule of five and subjected to MD simulation and relative binding free energy calculation. Six compounds manifest a significant docking score and strong binding interaction towards VP35 protein. MD simulations further confirmed the remarkable stability of these six complexes. Relative binding free energy calculations also showed significant ΔG value in the range of -132.3 and -49.3 kcal/mol. This study paves the way for further optimization of these compounds as potential inhibitors of VP35, facilitating subsequent experimental in vitro studies.Communicated by Ramaswamy H. Sarma.

Nanoparticle-Based Approaches for Treatment of Hematological Malignancies: a Comprehensive Review.

Blood cancer, also known as hematological malignancy, is one of the devastating types of cancer that has significantly paved its mortality mark globally. It persists as an extremely deadly cancer type and needs utmost attention owing to its negligible overall survival rate. Major challenges in the treatment of blood cancer include difficulties in early diagnosis, as well as severe side effects resulting from chemotherapy. In addition, immunotherapies and targeted therapies can be prohibitively expensive. Over the past two decades, scientists have devised a few nanoparticle-based drug delivery systems aimed at overcoming this challenge. These therapeutic strategies are engineered to augment the cellular uptake, pharmacokinetics, and effectiveness of anticancer drugs. However, there are still numerous types of nanoparticles that could potentially improve the efficacy of blood cancer treatment, while also reducing treatment costs and mitigating drug-related side effects. To the best of our knowledge, there has been limited reviews published on the use of nano-based drug delivery systems for the treatment of hematological malignancies. Therefore, we have made a concerted effort to provide a comprehensive review that draws upon recent literature and patents, with a focus on the most promising results regarding the use of nanoparticle-based approaches for the treatment of hematological malignancies. All these crucial points covered under a common title would significantly help researchers and scientists working in the area.

Advancements in gelatin-based hydrogel systems for biomedical applications: A state-of-the-art review.

A gelatin-based hydrogel system is a stimulus-responsive, biocompatible, and biodegradable polymeric system with solid-like rheology that entangles moisture in its porous network that gradually protrudes to assemble a hierarchical crosslinked arrangement. The hydrolysis of collagen directs gelatin construction, which retains arginyl glycyl aspartic acid and matrix metalloproteinase-sensitive degeneration sites, further confining access to chemicals entangled within the gel (e.g., cell encapsulation), modulating the release of encapsulated payloads and providing mechanical signals to the adjoining cells. The utilization of various types of functional tunable biopolymers as scaffold materials in hydrogels has become highly attractive due to their higher porosity and mechanical ability; thus, higher loading of proteins, peptides, therapeutic molecules, etc., can be further modulated. Furthermore, a stimulus-mediated gelatin-based hydrogel with an impaired concentration of gellan demonstrated great shear thinning and self-recovering characteristics in biomedical and tissue engineering applications. Therefore, this contemporary review presents a concise version of the gelatin-based hydrogel as a conceivable biomaterial for various biomedical applications. In addition, the article has recapped the multiple sources of gelatin and their structural characteristics concerning stimulating hydrogel development and delivery approaches of therapeutic molecules (e.g., proteins, peptides, genes, drugs, etc.), existing challenges, and overcoming designs, particularly from drug delivery perspectives.

Tiny titans- unravelling the potential of polysaccharides and proteins based dissolving microneedles in drug delivery and theranostics: A comprehensive review.

In recent years, microneedles (MNs) have emerged as a promising alternative to traditional drug delivery systems in transdermal drug delivery. The use of MNs has demonstrated significant potential in improving patient acceptance and convenience while avoiding the invasiveness of traditional injections. Dissolving, solid, hollow, coated, and hydrogel microneedles are among the various types studied for drug delivery. Dissolving microneedles (DMNs), in particular, have gained attention for their safety, painlessness, patient convenience, and high delivery efficiency. This comprehensive review primarily focuses on different types of microneedles, fabrication methods, and materials used in fabrication of DMNs such as hyaluronic acid, chitosan, alginate, gelatin, collagen, silk fibroin, albumin, cellulose and starch, to list a few. The review also provides an exhaustive discussion on the applications of DMNs, including the delivery of vaccines, cosmetic agents, contraceptives, hormone and genes, and other therapeutic applications like for treating cancer, skin diseases, and diabetes, among others, are covered in this review. Additionally, this review highlights some of the DMN systems that are presently undergoing clinical trials. Finally, the review discusses current advances and trends in DMNs, as well as future prospective directions for this ground-breaking technology in drug delivery.

Isolation, Identification, and Antibacterial Properties of Prodigiosin, a Bioactive Product Produced by a New Serratia marcescens JSSCPM1 Strain: Exploring the Biosynthetic Gene Clusters of Serratia Species for Biological Applications.

Prodigiosin pigment has high medicinal value, so exploring this compound is a top priority. This report presents a prodigiosin bioactive compound isolated from Serratia marcescens JSSCPM1, a new strain. The purification process of this compound involves the application of different chromatographic methods, including UV-visible spectroscopy, high-performance liquid chromatography (HPLC), and liquid chromatography-mass spectrometry (LC/MS). Subsequent analysis was performed using nuclear magnetic resonance (NMR) to achieve a deeper understanding of the compound's structure. Finally, through a comprehensive review of the existing literature, the structural composition of the isolated bioactive compound was found to correspond to that of the well-known compound prodigiosin. The isolated prodigiosin compound was screened for antibacterial activity against both Gram-positive and Gram-negative bacteria. The compound inhibited the growth of Gram-negative bacterial strains compared with Gram-positive bacterial strains. It showed a maximum minimum inhibitory concentration against Escherichia coli NCIM 2065 at a 15.9 ± 0.31 µg/mL concentration. The potential binding capabilities between prodigiosin and the OmpF porin proteins (4GCS, 4GCP, and 4GCQ) were determined using in silico studies, which are generally the primary targets of different antibiotics. Comparative molecular docking analysis indicated that prodigiosin exhibits a good binding affinity toward these selected drug targets.

Discovery of Novel Myristic Acid Derivatives as N-Myristoyltransferase Inhibitors: Design, Synthesis, Analysis, Computational Studies and Antifungal Activity.

In recent years, N-Myristoyltransferase (NMT) has been identified as a new target for the treatment of fungal infections. It is observed that at present, there are increased rates of morbidity and mortality due to fungal infections. Hence, a series of novel myristic acid derivatives were designed via molecular docking studies and ADMET studies by targeting NMT (N-Myristoyltransferase). The designed myristic acid derivatives were synthesized by converting myristic acid into myristoyl chloride and coupling it with aryl amines to yield corresponding myristic acid derivatives. The compounds were purified and characterized via FTIR, NMR and HRMS spectral analyses. In this study, we carried out a target NMT inhibition assay. In the NMT screening assay results, the compounds 3u, 3m and 3t showed better inhibition compared to the other myristic acid derivatives. In an in vitro antifungal evaluation, the myristic acid derivatives were assessed against Candida albicans and Aspergillus niger strains by determining their minimal inhibitory concentrations (MIC50). The compounds 3u, 3k, 3r and 3t displayed superior antifungal capabilities against Candida albicans, and the compounds 3u, 3m and 3r displayed superior antifungal capabilities against Aspergillus niger compared to the standard drug FLZ (fluconazole). Altogether, we identified a new series of antifungal agents.