The rise of microbes resistant to nearly all classes of antimicrobial drugs has become a severe public health problem in recent years. In this study, a new series of Schiff-base triazole hybrid derivatives was designed and synthesized and their in silico and biological evaluations were conducted to explore their antimicrobial potential. To gain deeper mechanistic insight, the synthesized compounds were subjected to a comprehensive computational workflow that included molecular docking, ADME profiling, DFT calculations, and MD simulations. Molecular docking studies revealed promising binding affinities ranging from -7.00 to -10.8 kcal/mol, placing these compounds on par with clinically established reference drugs in terms of target engagement. Among the series, compound 6j emerged as electronically favourable, exhibiting the lowest HOMO-LUMO energy gap (-0.15163 Hartree) as determined by DFT analysis, a characteristic often associated with enhanced chemical reactivity and biological interaction potential. The dynamic behaviour of the most promising protein-ligand complexes was further interrogated through 100 ns MD simulations, which confirmed robust structural stability throughout the simulation trajectory. Complementing these findings, ADME profiling established that the compounds fulfil the criteria outlined by Lipinski's Rule of Five, underscoring their suitability as orally bioavailable drug candidates. On the biological front, in vitro antimicrobial evaluation against a panel of clinically relevant bacterial and fungal strains yielded encouraging results. Compound 6j demonstrated meaningful antifungal activity, with MIC values spanning 500-1000 μg/mL, while compound 6d stood out for its potent antibacterial performance, achieving an MIC of 500 μg/mL. Collectively, these findings position Schiff-base triazole hybrids as structurally versatile and biologically promising scaffolds, warranting accelerated pharmacological exploration toward the development of next-generation antimicrobial therapeutics.

Introduction: Triazine scaffolds offer appealing models for developing enzymefocused therapies that can overcome resistance due to their structural flexibility and target selectivity. In this work, a short, chemically homogeneous series of 1,3-thiazine-substituted 1,3,5-triazine derivatives was subjected to an initial exploratory structure-activity relationship investigation and to molecular docking to investigate their possible dual-target binding interactions. Methods: A three-descriptor Multiple Linear Regression model was developed to correlate N, EHOMO, and SB parameters with experimental antimalarial activity (pIC50). Y-randomization and leave-one-out cross-validation were used to evaluate the model's robustness. Molecular docking was done against P. falciparum plasmepsin-II and DNA gyrase. Results: The MLR model demonstrated high structural homogeneity (R2 = 0.964; adjusted R2 = 0.948). Electronic descriptors, molecular polarisability, and topological variables all had a significant influence on predicted activity. Based on pIC₂⁽ values, compound 6j showed the highest predicted antimalarial efficacy. Compound 6e, on the other hand, showed the most advantageous and reliable dual-target binding interactions with DNA gyrase and Plasmepsin-II, suggesting it could be a good lead candidate for further optimization. Discussion: The results imply that the triazine scaffold's electronic and steric characteristics are essential for regulating antimalarial activity. A potentially complementary therapeutic approach is indicated by the identified enzyme-targeted binding profile, which differs mechanistically from traditional medications such as artemisinin and chloroquine. Conclusion: Compound 6j was the most active lead candidate for predicted antimalarial activity. To verify biological efficacy, experimental validation is necessary, as the study is computational and relies on a small dataset.

Introduction: Alzheimer's disease is characterized by a build-up of amyloid-β, tau hyperphosphorylation, neuroinflammation, synaptic dysfunction, and cognitive decline. Presently available treatments mostly alleviate symptoms with minimal impact on disease modification. To highlight the importance of phenotypic and pharmacogenomic stratification and investigate the therapeutic potential of repurposing medications in AD Methods: A narrative review was conducted through October 2025 using PubMed, Scopus, and Web of Science. Original research papers, reviews, and English-language Phase I–III clinical trials were all included. The agents were ranked according to their mechanistic justification, translational value, and current clinical data. Results: Repurposed agents include anti-inflammatory agents, metabolic modulators, immunomodulatory agents, neuropsychiatric agents, and autophagy-related derivatives. In preclinical and early clinical trials, several show neuroprotective or early diseasemodifying signals. On the other hand, the results of many trials are unclear or inconsistent. Variations in APOE genotype, metabolic state, vascular comorbidities, and sex differences may affect the response to treatment. Discussion: Repurposing drugs has several advantages, such as reduced development timelines, cheaper costs, and established safety records. However, restricted stratified trial designs, regulatory restrictions, and biological variability all impede translation. Clinical signal identification may be enhanced by biomarker-guided patient selection and early management, according to evidence. Conclusion: Repurposing drugs is a sensible and encouraging approach to developing treatments for AD. Efficacy must be verified by rigorous, meticulously designed, and stratified clinical trials prior to widespread clinical integration.

Infectious diseases are traditionally managed using medicinal herbs in traditional Chinese medicine, Ayurveda and Unani. These conventional therapies are an essential source of new anti-infective drugs considering antimicrobial resistance threatens global public health. The present review critically appraises the use of medicinal plants against bacterial, viral, fungal and parasitic infections in combination with medicinal chemistry and ethnopharmacology. A comprehensive review of ethnobotanical data, phytochemistry and pharmacological studies was performed on the basis of WHO classification of infectious diseases in order to identify repeating medicinal plants and their active ingredients. Over 150 medicinal plants have been discovered by major ethnomedical systems in the course of history and have been used as the remedy of infectious diseases. Essential phytochemicals such as alkaloids, terpenoids, flavonoids, phenolics and saponins showed broad-spectrum anti-infective activity via mechanisms including membrane damage, enzyme inhibition, oxidative stress regulation and interference with nucleic acid synthesis. Some examples of such successful combination of ethnopharmacology with pharmacology include artemisinin, berberine, andrographolide and glycyrrhizin. Nevertheless, the lack of standardization, poor bioavailability and insufficient clinical trials are still problematic.

The mitogen-activated protein kinase (MAPK) signaling pathway is a central oncogenic signaling axis, with BRAF functioning as a critical regulatory node. The discovery of oncogenic BRAF mutations, most notably BRAFV600E, enabled the development of targeted therapies that significantly improved clinical outcomes in several cancers. However, extensive preclinical and clinical investigations have revealed fundamental limitations of interpreting RAF signaling from a monomer-centric perspective. Rather than acting solely as an isolated kinase, BRAF exists in a dynamic equilibrium between inactive monomers and active dimers, with dimerization emerging as a major determinant of MAPK pathway output, therapeutic response, and resistance. In this review, we integrate structural, mechanistic, and translational evidence to establish BRAF dimerization as a central organizing principle of RAF signaling. These structural insights are placed in a disease context by examining how distinct classes of BRAF mutations constitutively active, dimer-dependent, or kinase-impaired converge on dimer-mediated MAPK activation. We further discuss molecular mechanisms that promote dimerization-driven therapeutic resistance, including alternative BRAF splicing, gene amplification, receptor tyrosine kinase RAS feedback activation, and scaffold-mediated stabilization of RAF dimers. Finally, we evaluate emerging therapeutic strategies targeting dimeric RAF complexes, including pan-RAF and dimer-compatible inhibitors, allosteric modulators, interface disruptors, and targeted protein degradation approaches, alongside mutation-class informed clinical trial designs and biomarker-adaptive strategies. Collectively, this review positions BRAF dimerization as a fundamental and therapeutically actionable feature of MAPK signaling, providing a structural and clinical framework for the development of durable RAF-targeted therapies beyond monomer inhibition.

Introduction: Thiadiazole derivatives have emerged as promising candidates for the development of novel antibacterial agents. The integrated QSAR–docking–ADME approach highlights thiadiazole derivatives as promising leads with stronger predicted activity than ciprofloxacin, warranting further In-vitro and In-vivo validation. Materials and Methods: A dataset of thiadiazole derivatives with known antibacterial activity was analyzed. 3D-QSAR using comparative molecular field analysis was performed to identify essential structural features. Docking studies were conducted to predict the binding interactions of selected thiadiazole derivatives with bacterial targets, focusing on key interactions, including hydrogen bonding and hydrophobic contacts Results: The QSAR analysis revealed significant correlations between the structural features of the compounds and their antibacterial activity. The 3D-QSAR analysis, utilizing comparative molecular field analysis, provided insights into the three-dimensional structural requirements for optimal antibacterial activity. Molecular docking studies predicted binding interactions between the thiadiazole derivatives and their potential bacterial targets. The results indicated that ligands 4, 5, 9, and 10 exhibited strong binding affinities, ranging from -8.9 to -9.5 kcal/mol. Ligand 4 demonstrated the highest binding energy (-9.5 kcal/mol) by forming hydrogen bonds and hydrophobic interactions at the E. coli effector site. Discussion: Thiadiazole derivatives showed enhanced predicted antibacterial activity over ciprofloxacin, supported by QSAR correlations and docking interactions. Compounds 4, 5, 9, and 10 exhibited the strongest binding energies, highlighting the scaffold's novelty. Further in-vitro and in-vivo validation remains essential for translational application. Conclusion: The integrated QSAR, docking, and ADME analysis identified thiadiazole derivatives, particularly compounds 4, 5, 9, and 10, as promising antibacterial leads with higher predicted binding affinity than ciprofloxacin. While computational findings provide valuable insights, experimental in vitro and in vivo validation is essential to confirm their therapeutic potential.

Plants serve as a revered base for the natural products that support human health. There is growing evidence that Ayurvedic medicinal herbs and the secondary metabolites they produce can be used to treat cancer. Numerous research have documented the value of herbal plants in immune system modulation, cancer patient survival, and quality of life. For the treatment and prevention of cancer, Ayurvedic herbal remedies are included into mainstream therapy. Humans are becoming more and more reliant on herbal remedies because they are safer and more potent than manufactured pharmaceuticals. The value of medicinal plants is rising due to its potential and uses. The use of Ayurvedic medicinal herbs for the prevention and treatment of various malignancies is examined in this chapter’s review work. This chapter also discusses a report on the potential use of phytoconstituents in the treatment of cancer.

Viral infections are increasing continuously, and we do not have proper treatment. Currently, the COVID-19 pandemic is an emerging threat globally. If we look into the Indian perspective against COVID-19, plant-based medicine available in ancient literature has been used, like Charaka Samhita and current ayurvedic pharmacopeia. Many viral diseases will come in the future, for which, there is a need to establish concept-based treatment with scientifically-proven pharmacological action. The plant's primary and secondary metabolites are responsible for pharmacological activities. Many plants have shown their efficacy in viral infections through their phytochemicals. In this chapter, we have conceptualized the same and identified the plants with their metabolites, which can be a direction for future research on viral disease. Currently available allopathic treatments have efficacy but toxicities too. For a better understanding of the diseases, the pathophysiology of the same is one of the components, as it gives a complete idea about how the viruses affect us. In the Indian traditional drug system, many folk medicines are available that need to establish the correlation with the targeted sites for a disease, which can give us the direction for future viral infections. The urgency is also to standardize these drugs for proper use among the global population. For identification, isolation of primary and secondary metabolites can help in treatment and drug targeting. The beauty of traditional medicine is that it is affordable because of its availability in different regions across the globe.

The field of pharmacology, dedicated to discovering, developing, and understanding the effects of drugs on living systems, has always been a dynamic and evolving discipline. From the early days of herbal remedies to the current era of precision medicine, constant innovation has driven progress in healthcare. Today, at the forefront of this evolution stands artificial intelligence (AI), poised to revolutionize the landscape of drug discovery and development. This chapter delves into the multifaceted role of AI in propelling the advancement of pharmacology, exploring its applications, potential, and the ethical considerations that accompany this powerful technology. This chapter provides a foundational overview of the role of AI in pharmacology. Each sub-section can be expanded upon with specific examples, case studies, and relevant research findings to provide a comprehensive understanding of the topic.

Arthritis is a global concern, affecting the global population, especially older people. The allopathic treatments proved their efficacy but toxicities too, so the need is to establish the treatment which should be productive and safe too. Many herbal-based medicines are used in the traditional medicine system, proving their effectiveness in the disease. The need of the hour is to establish their scientific, mechanical approach to arthritis treatment, which can improve the quality of life of these patients. In recent years, scientific research has shown that plant bioactive compounds are efficacious in disease treatment. This chapter aims to establish the knowledge of herbal medicines in disease treatment through the available scientific research data and their applicability. The plant-related drugs and disease knowledge are essential for treating disease. Ayurveda is the best and gold standard in terms of efficacy. Ancient literature like Ayurvedic Pharmacopeia and Chark Samhita have not only classified but also provided evidence-based knowledge on many diseases. In this chapter, we have conceptualized the various bioactive compounds from herbal drugs in their role in disease management treatment. The plant’s primary and secondary metabolites have massive potential for treating arthritis. We have discussed the targeted sites for the disease management and applicability of herbal drugs in arthritis through available scientific-based evidence.

Respiratory tract infections are a major health problem in the entire world, especially due to corona epidemic in late 2019. Coronavirus spread-out throughout the world, and it causes the death of millions of people due to the precipitation of severity in respiratory disorders like respiratory neuromuscular, pulmonary vascular, and lung parenchymal disorders. All are the characteristic features of COVID-19 infection. The aim of the present review work was to summarize all existing ethnobotanical data on ayurvedic medicinal plants used in the treatment or management of respiratory disorders. Many known plant species are traditionally used to treat respiratory disorders & some plant species have been investigated for their therapeutic efficacy with positive results. This present study explored various offline & online databases for the literature on ayurvedic medicinal plants used worldwide to treat & manage respiratory disorders. A total number of 205 ayurvedic plant species used to treat & manage respiratory disorders worldwide has been documented. Most of the plants belong to Solanaceae, Asteraceae, Amaryllidaceae, Lamiaceae & Malvaceae.

Background: To investigate the potential of anti-infl ammatory, antinociceptive, and antioxidant activity of diff erent extracts of Sida rhombifolia. Materials and Methods: The successive extraction of dried aerial parts of S. rhombifolia was performed with the help of the soxhlet apparatus by pet. ether, chloroform, acetone, ethanol and water were used as a solvent. Anti-infl ammatory activity was performed using the carrageenin-induced edema model in the rat paw method. Antinociceptive activity was performed using the mouse writhing and hot plate tests. Antioxidant activity was determined through the ability of hydrogen peroxide scavenging. Result: The ethanolic extract (200 mg/kg.) oral showed maximum anti-infl ammatory activity 51.42 (maximum, %inhibition) after 2 hours. The ethanolic extract (200 mg/kg.) oral showed maximum % inhibition of writhing 57.74 for writhing test and 2.15 ± 0.02 time (sec) of jumping for hot plate test. The ethanolic extract of the drug showed high scavenging (59.25%) of hydrogen peroxide. Conclusion: On successive extraction process of aerial parts of S. rhombifolia reported that diff erent ethanolic extracts are more eff ective as anti-infl ammatory, antinociceptive, and antioxidant activity, respectively.

Currently, analytical techniques play a crucial role in drug discoveries and isolation processes. Different advanced methods are available for screening natural resources into desirable forms. Among them, chromatographic techniques are the most reliable and applicable for small quantities of samples. Chromatography is a technique for separating mixtures that depend upon differential affinities of solutes between two immiscible phases. One of the phases is a fixed bed of a large surface area while other fluid flows through or over a fixed phase. The greatest utility of chromatography lies in its ability to separate mixtures of solutes so that several individual substances may be quantities isolated in a pure state. Separation and identification of a natural substance can be challenging. Natural substances are a mixture of different components with different physiochemical properties. They are available as natural sources in large to small quantities in the form of a mixture. Herein, we are trying to explain different types of chromatographic techniques and types of strategies adopted to identify and isolate natural substances.

Molecular docking is a chief tool for the revelation of drug and their evolution.Initiation about molecular docking technique and their use in drug discovery is very useful.The principles of molecular docking incorporate sampling algorithm and scoring function.The distinction in accessibility and functioning of docking software are also described.The application of flexible docking is mainly that incorporate flexibility in receptor are a obstacles for available docking methods.For the drug discovery the utilization and example of molecular docking are provided.

Background Diabetes mellitus (DM) is a growing disease across the world; diabetes is a complex metabolic disorder in which blood glucose concentration level increases and continue for a prolonged period due to a decrease secretion of insulin or action, resulting in the disorder of carbohydrate, lipid, and protein metabolism. The plant-related bioactive compounds have proven their efficacy with least toxicities and can be utilized for the disease treatment. Our objective is to elucidate the mechanism of action of plant bioactive compounds which can give future direction in diabetes treatment. Main body In this review paper, we briefly study more than 200 research papers related to disease and bioactive compounds that have therapeutic applicability in treatment. The plant contains many bio-active compounds which possess in vitro and in vivo anti-diabetic effect which may be responsible for the hypoglycaemic property by inhibiting the digestive enzyme i.e. alpha-amylase and alpha-glucosidase, by producing mimetic action of insulin, by reducing the oxidative stress, by showing antihyperglycemic activity and hypolipidemic activity, by inhibition of aldose reductase, and by increasing or enhancing glucose uptake and insulin secretion. Conclusion Our study revealed that terpenes, tannin, flavonoids, saponin, and alkaloids are important bioactive constituents for anti-diabetic activity. The mechanistic approach on alpha-glucosidase and alpha-amylase, hypolipidemic activity, and AR inhibitory action clear-cut explain the therapeutic applicability of these bioactive compounds in disease. Plants that contain these bioactive compounds can be good drug candidates for future research on diabetes treatment.

Introduction: Sida rhombifolia is a perennial plant & grows on tropical or subtropical lands.Sida rhombifolia belongs to Malvaceae family.Sida rhombifolia has various pharmacological actions as they contain biologically active compounds.Material & Methods: Pharmacognostical and quality control parameter involves study of macroscopic, microscopic, microchemical, TLC & Qualitative chemical examination of Sida rhombifolia Result: All pharmacognostical and quality control parameters of Sida rhombifolia were carried out.The morphological evaluations were done to ascertain the standard reference values for standardization of the plant materials where as the microscopy, the section study of the leaves of Sida rhombifolia shows the presence of xylem, fibers, trichomes, crystal, phylum, and anisocytic stomata is present.

The current study was focused on the investigation of anticancer activity of Scindapsus Officinalis fruit extract embedded silver nanoparticles (So-AgNPs) followed by anticovid activity prognosis of major phytocompounds, which participate in nanoformulation synthesis. The synthesis process involved the addition of AgNO3 solution (1 mM) and color change of the extract from light brown to dark, confirmed the formation of silver nanoparticles. Further, the characterization of synthesized So-AgNPs were done using different spectroscopical and microscopical techniques. FTIR spectra of So-AgNPs indicated vibrational peaks of polyphenolic hydroxyl groups, which are responsible for the stabilization of nanoformulation. Others microscopy methods such as SEM, TEM, XRD, and EDX illustrated that the synthesized So-AgNPs consist irregular size, spherical shape and thoroughly dispersed above the plane. Anticancer evaluation illustrated that the So-AgNPs have dose dependent anti-breast and anti-hepatic cancer activity (range of 97.72 +/- 0.42-54.86 +/- 0.46% cell viability), which were noticed more effective than raw fruit extract of Scindapsus Officinalis. The computational anticovid prediction of major phyto-compound of the extract [which designate as inhibitor 1: ((2R,3S,4S, 5R)-2-(hydroxymethyl)-6-(((1S, 5S)-1-methyl-5-(2-methylprop-1-en-1-yl)cyclopent-2-en-1-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol)] illustrated moderate tendency to interact with corona main protease enzyme (expected pIC > 6 mu M). However, the molecular docking and dynamics studies showed that selected compounds have moderate tendency to interact human dihydrofolate reductase and topoisomerase 1 enzyme. The accomplished approach shows that So-AgNPs with adsorbed phytocompounds on its surface consist valuable experimentally proved anticancer potency and computationally predicted anticovid effect. Thus, the formulation can be used as an alternative to the covid infected cancer population.

The aim of the current research was to investigate the anti-hepatic and anti-breast cancer activity of Polygonatum verticillatum rhizome extract embedded silver nanoparticles (Pv-AgNPs). The addition of AgNO3 (1 mM) in the process of synthesis, showed change in color of the rhizome extract from brown to dark brown, suggested the formation of silver nanoparticles. Further, FTIR spectra of Pv-AgNPs showed polyphenolic vibrational peaks of hydroxyl groups (3734 . 3367 cm(-1) range) that are responsible for the stabilization of nanoformulation. SEM, TEM, EDX, and XRD analysis showed that nanoparticles contain spherical shape, irregular size and well dispersed throughout the plane. Whereas, the elemental analysis results confirmed that 93.28% of Ag ions were present in the formulation. In-vitro anticancer evaluation showed that Pv-AgNPs (86.58 +/- 0.84-46.17 +/- 1.27% cell viability) have dose-dependent inhibition potency against HepG-2 and MCF-7 cancer cells lines. The comparison study also suggested that Pv-AgNPs consist higher anticancer efficacy than rhizome extract. Computational ADMET and topoisomerase activity prognosis showed optimal drug like properties of major phyto-compounds, which were adsorbed on the surface of silver during the synthesis of nanoformulation. Docking and molecular dynamics simulation study confirmed that the selected phyto-compounds anthraquinones, diosgenin, 5-hydroxymethyl-2-furaldehyde, and santonin have strong tendency to interact with the topoisomerase enzyme. The overall computational studies illustrated that phyto-compounds have mild tendency to act as anticancer agents but the experimental assay showed that in a combination such as whole extract of rhizome and Pv-AgNPs possessed significant potency against the breast and hepatic cancer.

The current research explains the development of a new method and its subsequent validation by a novel HPLC method in fluconazole tablets. Inertsil Octadecyl silica C18 column having dimensions of length 150 mm, diameter 4.6 mm, particle size 5 μm was exploited for the method development, and the mobile phase embodies buffer pH 4 and acetonitrile in the combo of 40:60. Wavelength exploited for the segregation was 289 nm. The volume of injection was preserved at 20 µl. The new developed method has been established to demonstrate linearity in the range of 10 to 30 µg /ml correspondingly. Average recovery established to be 101.571, 100.315, and 99.021, the standard deviation was established to be 0.93834, 0.986418, and 0.989741, and % R.S.D was established to be 0.92382, 0.98331, and 0.999526. The percentage recovery was established to be within prescribed restrictions. The limit of detection was established to be 0.0080. The limit of quantitation was established to be 0.0051. In assay studies, an average assay was found to be 95.966, and standard deviation and % RSD of the assay was found to be 0.6021 and 0.6274, respectively. The method was found to be specific as there was no intrusion from impurities and excipients. Extensive diversity of mobile phase combos was utilized for the research and flow rate preserved at 1.3 ml/min all through the process. After carefull and systemic investigation of various research articles and review articles, it is observed that H.P.L.C method development and validation of fluconazole has been done in various pharmaceutical dosage forms, but till now a smaller amount of work is executed on dosage forms of solid nature, and hence there is huge prospective for research to be done in this area for new methodology to be developed in pharmaceutical dosage form of solid nature by means of dissimilar mobile phase combos and different strategy adopted by use of chromatography software which avoids the problems and demerits associated with present methods