Introduction: Antimicrobial resistance, particularly when associated with biofilm formation, represents a major global health challenge. In this context, this study aimed to design, synthesize, and evaluate the in vitro biological activity of (E,E)-farnesylethane-1,2-diamine (4a) and (E,E)-farnesylpiperazine (4b), as dihydrochloride salts. Methodology: The compounds were synthesized following literature protocols. Their antibacterial activity was evaluated by determining Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) against Staphylococcus aureus (ATCC 25923), methicillinresistant S. aureus (HU25), and Escherichia coli (ATCC 25922). Biofilm formation was evaluated under subinhibitory conditions by quantifying biomass and viable cells. Experiments were conducted in triplicate and analyzed statistically. Biofilm morphology was examined using Scanning Electron Microscopy (SEM). Results: (E,E)-Farnesol exhibited activity against Gram-positive strains (MIC 64 μg/mL for ATCC 25923 and 32 μg/mL for HU25), with no bactericidal effect (MBC >512 μg/mL), indicating a bacteriostatic profile. In contrast, derivatives 4a and 4b displayed bactericidal activity against both Gram-positive and Gram-negative strains (MIC/MBC 32-64 μg/mL; MBC/MIC = 1). In biofilm assays, compound 4b reduced viable cell counts by over 90% across all strains (P < 0.001), while 4a showed moderate inhibition. SEM analysis confirmed reduced biofilm density and morphological alterations, particularly in Gram-positive bacteria. Discussion: Structural modification of (E,E)-farnesol significantly enhanced antibacterial and antibiofilm activity. Its derivatives demonstrate therapeutic potential against multidrug-resistant bacteria. Limitations include restriction to in vitro assays; further in vivo and cytotoxicity studies are needed. Conclusion: Compounds 4a and 4b emerge as promising candidates for further development, although additional in vivo and toxicity studies are required.
Abstract: One potential drug with analgesic, anticancer, and immune-enhancing properties is the endogenous pentapeptide M-ENK (opioid growth factor, OGF). A significant problem limiting its therapeutic application is its low bioavailability and short half-life in human plasma. Therefore, new analogues, as well as suitable delivery vehicles and administration routes for these potential drugs, are being sought. This article reviews the synthesis methods for OGF and its analogues, as well as the structure-activity relationships. Among other things, it describes: Compounds obtained by shortening or modifying the amino acid sequence in the peptide chain, methylated derivatives, compounds with hydrazine and phenylhydrazine, and with quercetin and resveratrol, which exhibit antioxidant properties, as well as derivatives containing bifunctional adamantane analogs, glycosylated derivatives with increased bioavailability, derivatives containing trifluoromethylamino acid residues in the G2 or G3 position, alkylamide derivatives, cyclic analogs containing thiazoles, cyclic peptidomimetic analogs, and the OGF-Gem conjugate. The M-ENK nanocarrier with RGD molecules is also presented for the controlled delivery of OGF to cancer cells. We highlight OGF and its derivatives in anticancer, analgesic, and immunomodulatory studies, and the potential for use in the treatment of other diseases, such as neurodegenerative (Alzheimer's, Parkinson's), diabetes, and viral diseases. The therapeutic potential of OGF is very large; therefore, it can be expected that the synthesis of new analogues and conjugates with used chemotherapeutic agents will be continued.
Abstract: Unexpected findings emerge when nature encounters pandemic challenges. From mountain slopes, remedies arise shaped by harsh climates. Such conditions foster strong chemical defenses in plants. One such defense disrupts a key virus enzyme, similar to lab-made drugs. Instead of only attacking germs, these substances also calm body reactions gone awry. They can block the spike protein's interaction with human cells while reducing excessive immune signals associated with severe illness. Structural features within these compounds may explain why some are more effective than others. Tiny carriers developed through advanced methods help them reach target sites more effectively. Evidence has accumulated gradually across recent studies. Not every plant compound is equally successful, as effectiveness depends on precise molecular interactions and stability within the body. Delivery may be as important as the compound's origin or structure. Insights come not from individual experiments alone, but from patterns observed across multiple studies. Most importantly, different levels of evidence are distinguished here, ranging from lab experiments and computer forecasts to animal tests and limited human research, with the awareness that digital results often fail in real medical settings unless confirmed through rigorous testing. Rooted in traditional plant knowledge yet guided by modern methods, this study maps a path toward discovering natural remedies while maintaining a critical assessment of whether the reported health benefits are supported by sufficient evidence.
Introduction: There are several problems with cutaneous or transdermal drug delivery, including suboptimal drug penetration, an insufficient amount of time for the drug to remain at the target, and drug instability. In response to intrinsic biological stimuli in diseased epidermal tissues, stimuli-responsive nanocarriers also called intelligent or smart delivery systems emerged to overcome these limitations and deliver various therapeutic agents. Methods: In this study, the literature on internal stimuli-responsive nanocarriers for dermal and transdermal delivery reported in review articles/research articles from 2015 to 2026 was reviewed using Google Scholar, ScienceDirect, and PubMed as the primary databases. Relevant patents were identified by using Espacenet and Google Patents. There was no systematic quantitative synthesis, but important data were presented following qualitative synthesis. Results: Enzyme-responsive systems for hyaluronidase, matrix metalloproteinases, and lipases were developed for targeted drug delivery to infection and inflammation sites. pH-sensitive nanocarriers used the acidic change in diseased skin for enhanced penetration and improved therapeutic efficiency. Glucose-responsive systems are promising to facilitate the targeted delivery of drugs to promote healing of diabetic wounds in hyperglycemia. Furthermore, drug delivery was controlled by redox-sensitive transporters, which benefited from the high levels of glutathione and reactive oxygen species in inflammatory skin. Discussion: Longer cutaneous residency, less systemic exposure, and lower therapeutic dosages may explain why these smart systems may outperform conventional formulations. A relatively new development in dermatological care is the integration of multiple response systems into one platform. Conclusion: Internal stimuli-responsive nanocarriers are an alternative strategy for the treatment of skin diseases by combining the delivery of drug molecules with disease-specific biological signals. This new strategy may enable safer and more efficient dermal and transdermal delivery of a wide range of medicinal compounds.
Despite significant progress in the global fight against HIV/AIDS, the disease is still a serious public health problem around the globe. Current ARV therapy (ART) has transformed HIV into a chronic illness from a death sentence; however, limitations such as low drug bioavailability, off-target toxicity, resistant strain development, and the presence of latent viral reservoirs are still major hurdles to elimination. In the last few years, nanochitosan (NCH) has gained increasing attention as a multifunctional and biocompatible nanomaterial with the promise of fulfilling these unmet clinical demands. Its inherent properties of mucoadhesion, antimicrobial activity, biodegradability, and immunomodulation place NCH in the most suitable position as a prospective agent for HIV prevention and treatment. NCH could serve as a carrier for directed and controlled delivery of antiretroviral (ARV) agents, enhance residence time at mucosal sites, and increase penetration through biological barriers to augment therapeutic effectiveness and minimize systemic toxicity. Its cationic properties also allow direct interaction with the viral envelope's negative charge, potentially inhibiting viral entry and replication. This review critically examines recent advances in NCH-based approaches, including prophylactic products such as intravaginal gels and films, targeted ART delivery systems for latent reservoirs, and new insights into NCH's direct antiviral activity. Lastly, the potential role of mathematical modeling in predicting viral load behavior and in justifying dosing regimens quantitatively is debated. Translational hurdles of paramount concern, e.g., large-scale production, long-term safety, regulatory approval, and cost-effectiveness, are also addressed. By uniting nanotechnology, virology, and systems pharmacology, this article positions NCH as a next-generation platform capable of revolutionizing HIV prevention and treatment worldwide
Cardiovascular Diseases (CVDs) are still the leading cause of illness and death worldwide, even though there have been improvements in traditional treatments. Current therapies, such as medications and surgeries, often have limitations like side effects, high costs, and inconsistent effectiveness. Herbal medicine has a long history of use in traditional systems and offers a wide range of natural compounds that may protect the heart. However, there are challenges in using herbal medicine clinically, including poor absorption in the body, instability of active ingredients, and inability to target specific areas. A new approach called herbal nanopharmacology combines the benefits of herbal medicine with nanotechnology to overcome these obstacles. This field is still relatively unexplored, especially regarding specific CVDs. The important aspects cover the epidemiology and pathophysiology of CVDs, herbs and their therapies, alongside the most recent advances in medicine. Specific conditions such as hypertension, atherosclerosis, and myocardial infarction are further examined in terms of the application of herbal nanopharmacology, with supporting preclinical and clinical evaluation with safety assessment. This article discusses the need for additional research and development of hybrid medicine, combining nanobiotechnology and herbal medicine, to treat conditions such as CVDs. This review aims to reduce the burden by collating salient points from various studies on herbal nanopharmacology and bioactive compounds for the prevention and treatment of CVDs. It assimilates work in the field on bioactive constituents, their modes of action, and principles of nanotechnology in medicine.
Introduction: The purpose of this study was to analyze the anti-inflammatory potential of the phytochemical constituents of Turpinia montana Kurz, with a focus on nitric oxide (NO) inhibition and potential synergistic effects among isolated substances. Methods: The chemicals were isolated from methanolic extracts of T. montana leaves and twigs using combined chromatographic methods. The ability of each compound to decrease NO generation in RAW 264.7 macrophages activated with LPS was examined. Combination tests were used to further evaluate synergistic interactions, and the Chou–Talalay method was used for quantitative analysis. Results: One new flavonol glucoside, 7-O-(1,1-dimethyl-3-oxobutan-1-y1)kaempferol 3-O-β-Dglucopyranoside (1) and seven known compounds, kaempferol 3-O-β-D-glucopyranoside (2), 2α,3β,19α-trihydroxy-5α,9α-urs-12-en-28-oic acid-28-O-β-D-glucopyranosyl ester (3), pedunculoside (4), rotungenoside (5), quadranoside III (6), urolic acid (7), and icariside E3 (8) were isolated. Moderate NO inhibitory activity was demonstrated by compounds 1, 3, and 4. Increased effects were found in combination experiments, especially for the combination Comp.1/Comp. 4, which showed consistent synergy with DRI values of roughly 4–9. Discussion: The anti-inflammatory properties of T. montana may result from the consequence of synergistic interactions between its ingredients. It may reflect the value of combination-based phytochemical approaches. conclusion: Overall, the isolation of the new compound 1 and the characterization of its quantitative synergy (CI, DRI) with compound 4 collectively validate the anti-inflammatory therapeutic potential of T. montana. These findings also emphasize that synergistic interactions among isolated compounds play a critical role in the anti-inflammatory activity of T. montana, providing a rational basis for further exploration of combination-based phytochemical strategies. Conclusion: The study confirms the anti-inflammatory properties of T. montana leaves and twigs. The overall bioactivity may be partially attributable to synergistic interactions.
Type 1 diabetes (T1D) continues to be a complex, multifactorial autoimmune condition characterized by targeted destruction of pancreatic β-cells and permanent insulin dependence. How tremendous the change has been since the advent of insulin therapy, yet T1D patients remain at catastrophic risk from acute complications and chronic vascular injury, calling for more potent disease-modifying therapies. Developments in immunology and genetics have unraveled the interaction of environmental trigger events, including viral infection and gut microbiota, with genetic susceptibility, i.e., HLA class II alleles, on the aberration of immune tolerance and induction of β- cell autoimmunity. The last few decades have seen remarkable advances in the pathogenesis of T1D, including the discovery of β-cell autoantibodies and the pivotal role of autoreactive T cells. However, therapeutic trials in humans of immunomodulatory interventions, such as cyclosporine, anti-CD3 antibodies, and tolerogenic dendritic cells, have, to date, shown only temporary preservation of native insulin secretion, with safety limitations or failure to sustain efficacy being significant limitation. In parallel, efforts at inducing antigen-specific tolerance and microbiota modification have been promising in preclinical models but are still to be validated in humans. Technological advances, including continuous glucose monitoring and artificial pancreas systems, have enhanced glycemic management and quality of life without influencing causative autoimmunity. New strategies, β-cell replacement by transplant or xenograft, genetic engineering to favor immune evasion, and gene therapy for insulin production promise more definitive cures, but much remains in the path of safety, immune rejection, and long-term efficacy. Finally, in the years to come, the management of T1D will be a blend of early diagnosis, customized immunomodulation, improved sensing of glucose, and regeneration. Research on the genetic, immunologic, and environmental determinants for T1D and the creation of safer and more potent therapies will continue to be needed to advance beyond disease symptomatology management to disease modification and prevention.
As the field of anticancer drug development is constantly changing, combining synthetic lethality with epigenetic modifiers opens up new possibilities for targets that fall outside the traditional drug target range. Enzymes involved in DNA methylation and histone modification are examples of epigenetic modifiers that promote gene expression without altering the DNA sequence of the gene. These mechanisms play a key role in carcinogenesis when they are altered, as they downregulate tumor suppressor genes and overexpress oncogenic pathways. Synthetic lethality is a phenomenon in which simultaneous mutations or perturbations of two genes result in cell death, but alterations to one gene alone do not cause cell death. It was first observed in genetic research conducted on model organisms, such as fruit flies and fungi. The most well-known example of this idea from the perspective of cancer treatment is PARP inhibitors, which are effective in tumors with BRCA1/2 mutations, where further failure of DNA repair results in cell sensitization. Building on the concept of synthetic lethality, current research focuses on exploiting epigenetic flaws that are common in cancer cells. For example, when chromatin remodelers or methyltransferases cease to function, malignant cells undergo genetic rewiring, rendering them vulnerable to treatment. Recent research has produced some striking examples of synthetic-lethal drug interactions and biomarkers used in metagenomics for personalized medicine by targeting the secondary pathways used by cancer cells as a result of primary loss-of-function mutations, which selectively kill cancer cells while sparing healthy cells. The discovery of actionable epigenetic dependencies and overcoming tumor heterogeneity remain the largest challenges in translating these fascinating scientific discoveries to the clinic. The convergence of epigenetic modulators with synthetic-lethality-based therapeutic architectures is poised to define a transformative paradigm in precision oncology. By orchestrating multilayered perturbations across chromatin-regulatory networks, DNA damage-response pathways, and context-specific vulnerability nodes, this integrative strategy surpasses the limitations of conventional target-centric pharmacology and enables mechanistically rational, synergistic antitumor interventions.
INTRODUCTION:Optimal therapeutic control of Type 2 Diabetes (T2D) depends on designing Alpha-Glucosidase Inhibitors (AGIs) with high potency. This study employs a rigorous computational approach to evaluate 1-deazapurine-derived ligands, examining their interaction modes and pharmacochemical attributes. METHODS:The methodology involves drug-likeness evaluation, molecular docking, and Molecular Dynamics (MD) simulations to elucidate the thermodynamic stability of the complexes. A key feature is the integration of a detailed Structure-Activity Relationship (SAR) analysis, demonstrating high consistency between computational rankings and established biological inhibitory profiles. RESULTS:The screening revealed that heteroaromatic rings and bulky aromatic moieties were critical structural determinants for potency. Among the screen compounds, 6-(2-hydroxybenzoyl)-3- (2-phenylethyl)imidazo[4,5-b]pyridine-5-methyl carboxylate (L14), 5-(furan-2-yl)-3-(4- methoxybenzyl)-2-phenyl-7-(trifluoromethyl)imidazo[4,5-b]pyridine (L11), and 3-[2- phenylethyl]-5-thiophene-2-yl-7-(trifluoromethyl)imidazo[4,5-b]pyridine (L4) stood out for their optimal binding affinities. In particular, L11 emerged as the most significant candidate due to its superior interaction energy and structural stability, directly reflecting observed biological trends. DISCUSSION:These results, supported by favorable ADMET profiles, provide a robust scientific rationale for these ligands as lead compounds for T2D management. While the computational insights are highly consistent with observed trends, further studies will address any potential limitations before progressing. CONCLUSION:This study establishes a solid methodological framework for future in vitro and in vivo experimental validation of 1-deazapurine derivatives as potent therapeutic agents.
Introduction: Hybrid Nanosystems (HNSs) are a type of advanced drug carrier that can be made from various materials, including organic compounds, inorganic particles, lipids, polymers, and biomimetic components. This combined framework facilitates functionalities such as medication distribution, imaging support, and modification of therapeutic responses. This renders them highly promising for oncological therapy. The main goal of this study was to identify studies on HNSs that investigated their development, underlying characteristics, and therapeutic efficacy Methods: A comprehensive review of the literature was performed, utilizing platforms such as Google Scholar, Scopus, Web of Science, and PubMed. It systematically collected data on various aspects, including cancer types studied, nanomaterial compositions, targeting techniques, combination therapies, safety profiles, and therapeutic significance. The analysis encompassed findings from 197 preclinical and clinical studies published between 2010 and 2025. This study highlights recent advancements in cancer treatment methods, their mechanisms of action, and the critical challenges that must be addressed prior to clinical application. Results: The findings indicate that HNSs are under investigation for several cancer types, including breast, lung, liver, colon, and brain tumors. These technologies facilitate targeted drug delivery, initiate programmed cell death (apoptosis), inhibit cancer proliferation, and assist in real-time imaging for diagnostic applications. An analysis of 197 research papers published from 2010 to 2025 revealed that HNSs markedly improve anticancer efficacy by optimizing drug transport, tumor targeting, and multimodal therapy strategies. HNS-based systems attained tumor suppression rates of 70-90%, enhanced apoptosis, diminished systemic toxicity, and successfully addressed multidrug resistance and immune evasion. Multifunctional platforms that integrate chemotherapy, phototherapy, gene therapy, and immunotherapy have shown significant synergistic effects, with combination indices between 0.4 and 0.8. Despite the highly encouraging preclinical results, additional studies are necessary to evaluate long-term safety, scalability, and regulatory obstacles for effective clinical translation. Discussion: The results highlight the growing promise of hybrid nanostructures as sophisticated cancer therapies that can combine targeted delivery, multimodal treatment, and diagnostic capabilities on a single platform. Their capacity to overcome significant drawbacks of traditional medicines, such as multidrug resistance, inadequate bioavailability, and off-target toxicity, highlights their translational significance. Nonetheless, additional endeavours are necessary to ensure long-term safety, manufacturing uniformity, and regulatory structures to enable effective clinical implementation. Conclusion: Hybrid nanostructures have emerged as promising multifunctional platforms for cancer therapy, exhibiting increased tumour targeting, improved therapeutic efficacy, and diminished systemic toxicity across many cancer types. Their capacity to amalgamate drug administration, imaging, and combination therapies provides considerable benefits compared to traditional treatments. Nonetheless, thorough long-term safety investigations, scalable production methodologies, and defined regulatory frameworks are crucial to expedite their effective clinical translation.
Introduction: Antimicrobial resistance (AMR) remains a major global health threat driven by β-lactamase-mediated antibiotic hydrolysis, RND-family efflux pump overexpression, horizontal gene transfer, and biofilm-associated phenotypic tolerance. ESKAPE pathogens also combine various resistance mechanisms to survive the majority of antibiotic classes, and poor use of antibiotics maintains selection pressures and promotes the rapid development of multidrug resistance. Methods: We searched peer-reviewed articles in PubMed, Web of Science, Elsevier, and articles indexed in Nature. The ten mechanical categories of therapeutics were assessed, including antivirulence agents, efflux pump inhibitors, biofilm disruptors, quorum-sensing disruptors, CRISPR antimicrobials, bacteriophage therapy, antimicrobial peptides, nanocarrier systems, antibiotic hybrid and potentiator, riboswitch-targeted agents, molecular targets and clinical development status were assessed. Results: FDA-approved agents such as bezlotoxumab and β-lactam/β-lactamase inhibitor combinations, including ceftazidime-avibactam and meropenem-vaborbactam, showed activity against carbapenem-resistant Enterobacterales. CRISPR-engineered bacteriophage LBP-EC01 and chosen antimicrobial peptides are in Phase II/III clinical trials, and riboswitch ligands and antibiotic-peptide hybrids are proving to be preclinically effective with less selection favoring resistance. Discussion: Efflux pump inhibitors are not yet approved due to host transporter cross-reactivity, toxicity, and pharmacokinetic limitations. CRISPR and phage systems have limitations of delivery and uncertainty of regulation, which makes them very unsuccessful during approval. Conclusion: Innovative antimicrobial approaches present groundbreaking options compared to conventional antibiotics by focusing on the mechanisms of pathogenicity instead of merely aiming to eliminate bacteria, which in turn diminishes the selective pressure that leads to the emergence of resistance. The integration of these novel strategies signifies a significant transformation towards sustainable, precision-focused antimicrobial treatment crucial for tackling the worldwide AMR challenge.
Lipid-based nanocarriers, such as liposomes, niosomes, ethosomes, transferosomes, solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsions, have gained significant interest in targeted drug delivery. In brain-targeted delivery, these nanosystems can be beneficial if given by the intranasal route. They can overcome the issue of poor drug distribution to the brain by conventional systems. Colloidal vesicles permeate the nasal mucosa due to their small size and resemblance to the structure of the cell membrane. Other lipid carriers permeate through the nasal mucosa due to their nanosize and higher partition to cellular lipids. Several studies have established the intranasal nanocarrier-based drug delivery, the improved drug distribution to the brain and enhanced cognitive function in animal models. All lipid-based nanocarriers have shown such significant improvement in in vitro or in vivo studies. However, there is a gap between the lab-scale development and its industrial application. This review will highlight the outcome of reported studies on brain targeting by intranasal lipid-based nanosystems. It will help future researchers to identify the potential of individual systems and focus on the ‘gaps’ for their successful clinical translation.
Introduction: Indole derivatives are promising candidates for anticancer drug discovery due to their occurrence in biologically active molecules and their ability to modulate cellular targets. This study aimed to evaluate the antiproliferative effects, biomolecular interactions, and topoisomerase inhibition potential of four indole-thiazolidinone derivatives. Methods: DNA and HSA binding were investigated by UV-Vis absorption, fluorescence spectroscopy, and molecular docking. Topoisomerase inhibition was evaluated in vitro. Antiproliferative activity and effects on cell migration were assessed in human cancer cell lines using the sulforhodamine B (SRB) and wound healing assays, respectively. Results: The bis-indole derivative (4a) showed the strongest affinity for DNA (Kb = 1.34 × 10⁶ M⁻¹) and HSA (Kb = 1.30 × 10⁶ M⁻¹), altering the IIA hydrophobic microenvironment. In vitro, 4a displayed potent antiproliferative activity against MCF-7 breast cancer cells (GI₅₀ = 4.53 μM) and inhibited cell migration by 11.65% at 1 μM. No significant inhibition of topoisomerase I and II was observed at 10 and 50 μM. Discussion: The findings suggest that the cytotoxic activity of compound 4a is more closely associated with its interaction with DNA than with topoisomerase inhibition. Spectroscopic and computational analyses indicated the occurrence of multiple binding modes with DNA and HSA, supporting its favourable interaction profile. Furthermore, the high affinity for HSA may contribute to compound transport and distribution in biological systems, while the observed reduction in cell migration indicates a potential effect on tumour progression. Conclusion: Compound 4a is the most active in the series, representing a significant starting point for the development of new derivatives with potential anti-tumour activity.
Abstract: Glycogen synthase kinase-3β (GSK-3β) is a key regulator of the pathogenesis of Alzheimer's disease (AD), capable of simultaneously modulating core pathological processes such as amyloid-β (Aβ) deposition, tau protein hyperphosphorylation, synaptic damage, and neuroinflammation. Therefore, it has become one of the core druggable molecular nodes for AD intervention. This review is mainly divided into two parts. The first part focuses on the GSK-3β inhibitors that have been validated in AD-related cell and animal models. These inhibitors are specifically classified into four categories: metal ion-based compounds, adenosine triphosphate (ATP)-competitive inhibitors, non-ATP-competitive inhibitors, and multi-target inhibitors. The second part focuses on GSK-3β-specific positron emission tomography (PET) radioligands, which can non-invasively monitor GSK-3β enzyme activity in vivo, providing quantitative in vivo molecular imaging tracers for the study of AD pathogenesis and quantitative assessment of treatment effects. This review systematically summarizes GSK-3β-related inhibitors and PET radioligands in AD, thereby providing key references for the rational design of next-generation AD therapeutic drugs and diagnostic agents.
Breast cancer is one of the most common causes of cancer death among women in the world, and the number of tumors that depend on hormones occupies a significant percentage of cases that are diagnosed. The estrogen factor is central to the development of these cancers; hence, aromatase, the central enzyme involved in estrogen production, is a critical therapeutic target. Aromatase Inhibitors (AIs), in particular, have emerged to play an important role in endocrine therapy in postmenopausal breast cancer patients. Heterocyclic compounds, in particular, have also been receiving significant focus in the design of AI scaffolds, because they are structurally diverse and capable of binding the heme iron in the aromatase active site. This review provides extensive coverage of recent developments in heterocyclic aromatase inhibitors, including large classes such as azoles, indoles, quinolines, coumarins, benzofurans, and other fused heterocyclic systems. The focus is on trends in Structure-Activity Relationships (SAR), with emphasis on the patterns of substitution and pharmacophoric features that can modulate potency and selectivity. Mechanistic information from molecular docking and other computational studies is also presented to elucidate binding interactions and inform rational drug design. In addition, new approaches such as the development of hybrid molecules and multi-target-directed ligands are listed to illustrate emerging trends aimed at enhancing efficacy and pharmacokinetic properties. Together with heterocyclic structures, these frameworks are still offering viable and bright platforms on which next-generation aromatase inhibitors can be developed to treat breast cancer better.
In the originally published article entitled "Antibody-aptamer Complementation: Advancing Biosensing for Disease Monitoring", published in "Current Topics in Medicinal Chemistry" Vol: 26 Issue: 03 [1], a duplication inadvertently appeared in the heading of the original version of the article, which has now been removed. The original article can be found online at: https://www.eurekaselect.com/article/148862 Details of the error and a correction are provided here: ORIGINAL 4.2. Characteristic and Structural Variation of Aptamer of Aptamer CORRECTED 4.2. Characteristic and Structural Variation of Aptamer We apologize for any inconvenience caused to the readers.
The Quorum Sensing (QS) system plays a central role in regulating several processes that influence bacterial physiology, communication, and pathogenesis. It governs the production of virulence factors, facilitates biofilm formation, and contributes to the development of antibiotic resistance, all of which are critical to bacterial survival and pathogenicity. QS enables both intraspecies and inter-species bacterial communication, operating through distinct pathways in Gram-positive and Gram-negative bacteria. This review provides a comprehensive overview of the major families of quorum-sensing proteins involved in the working of the signalling molecules. It examines the structural features, functional roles, and mechanisms of action of these proteins, highlighting their significance in bacterial behaviour. Furthermore, the study explores the potential of plant-derived secondary metabolites as natural inhibitors targeting QS systems to disrupt bacterial pathogenicity. Finally, it discusses the implications of exploiting these inhibitors as promising strategies to address the growing challenge of antibiotic resistance in bacterial infections.
INTRODUCTION:Nerve Injury (NI) imposes a severe clinical burden involving energy failure, neuroinflammation, oxidative stress, and apoptosis. This review aims to systematically synthesize structural insights into AMP-activated protein kinase (AMPK), elucidate its multifaceted molecular mechanisms in NI, and evaluate AMPK-targeted pharmacological interventions. METHODS:A comprehensive literature search across major databases (PubMed, Web of Science, Scopus, and Google Scholar) identified peer-reviewed in vitro and in vivo studies focusing on AMPK mechanisms, structural pharmacology, signaling networks (e.g., AMPK/mTOR, AMPK/SIRT1), and drug targeting in various neural injury models. RESULTS:Upon cellular energy deficit, AMPK induces neuroprotective autophagy via the AMPK/mTOR/ULK1 axis and combats oxidative stress and neuroinflammation by promoting PGC-1α-mediated mitochondrial biogenesis and suppressing NF-κB. Conversely, AMPK dysregulation exacerbates neuronal death. Pharmacological agents demonstrate robust preclinical neuroprotection, though clinical application is hindered by off-target systemic toxicity and poor Blood-Brain Barrier (BBB) permeability. DISCUSSION:The findings highlight AMPK as a pivotal modulator of interconnected metabolic stress response cascades. While pharmacological agents demonstrate robust preclinical neuroprotection, their clinical application is currently hindered by off-target systemic toxicity, lack of isoform specificity, and poor blood-brain barrier (BBB) permeability. CONCLUSION:AMPK represents a highly promising therapeutic target for mitigating NI. Translating preclinical successes into clinical practice demands rigorous Structure-Activity Relationship (SAR) optimization to develop CNS-penetrant, isoform-selective modulators, thereby maximizing targeted neuroprotection while minimizing adverse systemic effects.
Diabetes mellitus (DM) is characterized by hyperglycemia, insulin resistance, and pancreatic β-cell failure, necessitating novel treatments. Garcinia atroviridis, rich in hydroxy citric acid (HCA), flavonoids, and polyphenols, shows potential against diabetes. In vitro and in vivo studies assessed its effects on glucose absorption, enzyme inhibition, and glycemic control in diabetic rats. The extract exhibited significant total phenolic (10.09 ± 0.24 mg GAE/g) and flavonoid (9.44 ± 0.11 mg QE/g) content. It demonstrated moderate direct antioxidant activity (DPPH IC₅₀ 15.14 ± 0.55 mg/mL) and inhibited α-glucosidase, α-amylase, and DPP-4 (IC₅₀ 35.04 ± 0.22 mg/mL, 22.21 ± 0.13 mg/mL). Crucially, in L6 myoblast cells, it enhanced glucose absorption (165.25% at 62.5 µg/mL) without cytotoxicity (IC₅₀ 3.12 ± 0.027 mg/mL). In diabetic rats, G. atroviridis (400 mg/kg) significantly reduced fasting blood glucose (69.33 mg/dL by day 21) and improved glucose tolerance. The findings suggest that the antidiabetic potential of G. atroviridis is likely driven by a multi-mechanistic synergy between its moderate direct antioxidant capacity, enzyme inhibition, and, most notably, its potent ability to enhance cellular glucose uptake at low concentrations. This positions G. atroviridis as a promising natural adjunct for diabetes treatment, warranting further research into its active compounds and clinical applications.
