Personalized oncology in pheochromocytomas and paragangliomas: integrating genetic analysis with machine learning.

Pheochromocytomas and paragangliomas (PCCs/PGLs) are uncommon neuroendocrine tumors with a significant genetic tendency. Approximately 35-40% of these tumors are associated with genetic factors. The present study performed a thorough analysis using publicly accessible genetic and clinical data from the Cancer Genome Atlas (TCGA) to examine the involvement of six genes, namely GBP1, KIF13B, GPT, CSDE1, CEP164, and CLCA1, in the development of PCCs/PGLs. By employing multi-omics data, this study investigates the relationship between mutational patterns and the prognosis of tumors, focusing on the possibility of tailoring treatment methods to individual patients. The study utilizes Mutect2 to detect somatic mutations with high confidence in whole-exome sequencing data from PCCG samples. The study uncovers mild effects on protein function caused by particular mutations, including GBP1 (p.Cys12Tyr), KIF13B (p.Arg847Gly), and GPT (p.Gln50Arg). A random forest classifier uses mutational profiles to predict potential drug recommendations, proposing a focused therapy strategy. This study thoroughly analyzes the genetic mutations found in PCCs/PGLs, highlighting the significance of precision medicine in developing specific treatments for these uncommon types of cancer. This study aims to improve the understanding of the development of tumors and identify personalized treatment approaches by combining genetic data with machine learning analyses.

Exploring hypoxia-induced ncRNAs as biomarkers and therapeutic targets in lung cancer.

Lung cancer is a deadly disease, causing nearly 20 % of all cancer deaths globally. A key factor in lung cancer's development and resistance to treatment is hypoxia, a condition where tumor cells experience low oxygen levels. In this low-oxygen environment, special molecules called non-coding RNAs (ncRNAs) become critical players. NcRNAs, including lncRNAs, miRNAs, circRNAs, and siRNAs, control how genes function and how cells behave. Some ncRNAs, like HIF1A-AS2 and HOTAIR, are linked to the aggressive spread of lung cancer, making them potential targets for therapy. Others, like certain miRNAs, show promise as early detection tools due to their influence on tumor blood vessel formation and metabolism. This complex interplay between hypoxia and ncRNAs is crucial for understanding lung cancer. For example, circRNAs can control the activity of miRNAs, impacting how tumors respond to low oxygen. Additionally, siRNAs offer a potential strategy to overcome treatment resistance caused by hypoxia. By studying the intricate relationship between hypoxia and ncRNAs, scientists hope to uncover new biomarkers for lung cancer. This knowledge will pave the way for developing more effective and targeted treatments for this devastating disease.

Non-coding RNAs in meningitis: Key regulators of immune response and inflammation.

Non-coding RNAs (ncRNAs) contain circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and micro-ribonucleic acids (miRNAs). These RNAs receive good functionality in modulation of gene expressions & cellular roles. Recent research is shedding light on their pivotal roles in the pathophysiology of inflammatory meningitis, such as viral, fungal, or bacterial infections. This review addresses the intricate roles of non-coding RNAs (ncRNAs) that transcribe code-independent mRNA and other biological elements that control inflammation and immunological events extant during meningitis. ncRNAs, acting on a myriad of immune cell development, cytokine production, pathogen recognition, and so forth, finely orchestrate the host's immune response. Although lncRNAs and circRNAs are associated with gene networks regulating immune responses, miRNAs can precisely modulate the expression of pro- and anti-inflammatory cytokines. Moreover, ncRNAs have unique expression patterns in disease states and are stable in bio-fluids; therefore, they can serve as specific molecular biomarkers for meningitis concerning the diagnosis and prognosis. It might also be helpful to target ncRNAs as a therapeutic strategy to impact immune regulation and inflammation. Here, we review the current knowledge of how ncRNAs function in meningitis and discuss adopted approaches and perspectives and their implications for therapeutic strategies.

Long non-coding RNA HOTAIR: A biomarker and therapeutic target in urological tumors.

Long non-coding RNAs (lncRNAs) significantly influence gene regulation across epigenetic, transcriptional, and post-transcriptional levels through their interactions with DNA, RNA, and proteins. There is growing evidence of lncRNAs' critical roles in the emergence and progression of various diseases, including urological tumors (UTs), such as cancers of the kidney, bladder, and prostate. Research increasingly links lncRNA dysregulation to diverse cellular processes like invasion, metastasis, apoptosis, and chromatin remodeling. Among these, HOTAIR stands out for its pivotal role in oncogenesis, impacting treatment resistance, cell migration, proliferation, survival, and genomic integrity. This review provides an overview of HOTAIR's functions, its identification, and its biological significance. Furthermore, it delves into HOTAIR's involvement in UTs, underlining its potential as a therapeutic target and biomarker for innovative approaches to treating these cancers.

Non-coding RNAs in Parkinson's disease: Regulating SNCA and alpha-synuclein aggregation.

Parkinson's disease is one of the vital neurodegenerative ailments attributed to a rise in Alpha-synuclein proteins leading to the advancement of motor and cognitive deterioration. Interestingly, in PD lncRNAs, miRNAs and siRNAs are also key regulators of SNCA and alpha-synuclein aggregation. This review will focus on the roles of these three types of small RNAs in trebling the development of PD through regulating SNCA expression or alpha-synuclein protein mediating the RNA from acting. Parkinson's disease is defined by the build-up of alpha-synuclein protein resulting predominantly from the elevated expression level of the SNCA gene. Non-coding RNAs have gained broad appeal as fundamental modulators of gene expression and protein aggregation dynamics, with significant implications on the aetiology of PD. LncRNAs modulate SNCA transcription and edit epigenetic modifications, while miRNA target mRNA is involved in the stability and translation of count alpha-synuclein. Considering all these data, siRNAs can achieve the precise gene silencing effect that directly induces the downregulation of SNCA mRNA. This review also summarizes some recent reports about the interaction between these ncRNAs with the SNCA gene and alpha-synuclein protein, each through its independent in addition to synergistic mechanisms. This review highlights the possibility of therapeutic interventions to perturb SNCA expression to prevent alpha-synuclein aggregation via targeting ncRNAs that might be spun off novel drug development for PD.

Tau proteins and senescent Cells: Targeting aging pathways in Alzheimer's disease.

Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by abnormal accumulation of tau proteins and amyloid-ß, leading to neuronal death and cognitive impairment. Recent studies have implicated aging pathways, including dysregulation of tau and cellular senescence in AD pathogenesis. In AD brains, tau protein, which normally stabilizes microtubules, becomes hyperphosphorylated and forms insoluble neurofibrillary tangles. These tau aggregates impair neuronal function and are propagated across the brain's neurocircuitry. Meanwhile, the number of senescent cells accumulating in the aging brain is rising, releasing a pro-inflammatory SASP responsible for neuroinflammation and neurodegeneration. This review explores potential therapeutic interventions for AD targeting tau protein and senescent cells, and tau -directed compounds, senolytics, eliminating senescent cells, and agents that modulate the SASP-senomodulators. Ultimately, a combined approach that incorporates tau-directed medications and targeted senescent cell-based therapies holds promise for reducing the harmful impact of AD's shared aging pathways.

A Systematic Review on Biochemical Perspectives on Natural Products in Wound Healing: Exploring Phytochemicals in Tissue Repair and Scar Prevention.

Wound healing is a critical process in tissue repair following injury, and traditional herbal therapies have long been utilized to facilitate this process. This review delves into the mechanistic understanding of the significant contribution of pharmacologically demonstrated natural products in wound healing. Natural products, often perceived as complex yet safely consumed compared to synthetic chemicals, play a crucial role in enhancing the wound-healing process. Drawing upon a comprehensive search strategy utilizing databases such as PubMed, Scopus, Web of Science, and Google Scholar, this review synthesizes evidence on the role of natural products in wound healing. While the exact pharmacological mechanisms of secondary metabolites in wound healing remain to be fully elucidated, compounds from alkaloids, phenols, terpenes, and other sources are explored here to delineate their specific roles in wound repair. Each phytochemical group exerts distinct actions in tissue repair, with some displaying multifaceted roles in various pathways, potentially enhancing their therapeutic value, supported by reported safety profiles. Additionally, these compounds exhibit promise in the prevention of keloids and scars. Their potential alongside economic feasibility may propel them towards pharmaceutical product development. Several isolated compounds, including chlorogenic acid, thymol, and eugenol from natural sources, are undergoing investigation in clinical trials, with many reaching advanced stages. This review provides mechanistic insights into the significant role of pharmacologically demonstrated natural products in wound healing processes.

Rutin-Loaded Transethosomal Gel for Topical Application: A Comprehensive Analysis of Skin Permeation and Antimicrobial Efficacy.

This study conducts a systematic investigation of the creation and optimization of a rutin-loaded transethosome intended for topical use. The formulation's characteristics were thoroughly assessed for vesicle size (160.45 ± 1.98 nm), polydispersity index (0.235 ± 0.067), and zeta potential (-22.89 mV), with an entrapment efficiency and drug loading of 89.99 ± 1.55% and 8.9 ± 2.11%, respectively, and found to have a spherical shape by the use of transmission electron microscopy. The conversion to a gel suitable for application on the skin was carried out. The drug release form Opt-RUT-TE formulation (73.61 ± 2.55%) was significantly higher than that of release form RUT-suspension (34.52 ± 1.19%). The drug that permeated the skin from Opt-RUT-TEG (935.25 ± 10.49 µg/cm2) was significantly higher than the permeability from RUT-Suspension gel (522.57 ± 6.79 µg/cm2). Notably, tape stripping analysis revealed that the Opt-RUT-TE gel effectively penetrated the skin layers, with a higher concentration observed in the epidermis-dermis than in the RUT-suspension gel. The transethosomal gel exhibited favorable characteristics, highlighting its capacity to efficiently permeate the skin and suppress the growth of microorganisms, and Opt-RUT-TEG showed a higher microorganism inhibition zone (Gram-positive bacteria) than that of RUT-suspension gel. The investigation highlights the significant therapeutic possibilities of rutin in a transethosomal gel formulation for treating dermatological diseases by improving skin permeability and exhibiting antibacterial effects.

Elucidating molecular mechanism and chemical space of chalcones through biological networks and machine learning approaches.

We developed a bio-cheminformatics method, exploring disease inhibition mechanisms using machine learning-enhanced quantitative structure-activity relationship (ML-QSAR) models and knowledge-driven neural networks. ML-QSAR models were developed using molecular fingerprint descriptors and the Random Forest algorithm to explore the chemical spaces of Chalcones inhibitors against diverse disease properties, including antifungal, anti-inflammatory, anticancer, antimicrobial, and antiviral effects. We generated and validated robust machine learning-based bioactivity prediction models (https://github.com/RatulChemoinformatics/QSAR) for the top genes. These models underwent ROC and applicability domain analysis, followed by molecular docking studies to elucidate the molecular mechanisms of the molecules. Through comprehensive neural network analysis, crucial genes such as AKT1, HSP90AA1, SRC, and STAT3 were identified. The PubChem fingerprint-based model revealed key descriptors: PubchemFP521 for AKT1, PubchemFP180 for SRC, PubchemFP633 for HSP90AA1, and PubchemFP145 and PubchemFP338 for STAT3, consistently contributing to bioactivity across targets. Notably, chalcone derivatives demonstrated significant bioactivity against target genes, with compound RA1 displaying a predictive pIC50 value of 5.76 against HSP90AA1 and strong binding affinities across other targets. Compounds RA5 to RA7 also exhibited high binding affinity scores comparable to or exceeding existing drugs. These findings emphasize the importance of knowledge-based neural network-based research for developing effective drugs against diverse disease properties. These interactions warrant further in vitro and in vivo investigations to elucidate their potential in rational drug design. The presented models provide valuable insights for inhibitor design and hold promise for drug development. Future research will prioritize investigating these molecules for mycobacterium tuberculosis, enhancing the comprehension of effectiveness in addressing infectious diseases.

Cannabidiol and neurodegeneration: From molecular mechanisms to clinical benefits.

Neurodegenerative disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis are severe and life-threatening conditions in which significant damage of functional neurons occurs to produce psycho-motor malfunctions. NDs are an important cause of death in the elderly population worldwide. These disorders are commonly associated with the progression of age, oxidative stress, and environmental pollutants, which are the major etiological factors. Abnormal aggregation of specific proteins such as α-synuclein, amyloid-ß, huntingtin, and tau, and accumulation of the associated oligomers in neurons are the hallmark pathological features of NDs. Existing therapeutic options for NDs are only symptomatic relief and do not address root-causing factors, such as protein aggregation, oxidative stress, and neuroinflammation. Cannabidiol (CBD) is a non-psychotic natural cannabinoid obtained from Cannabis sativa that possesses multiple pharmacological actions, including antioxidant, anti-inflammatory, and neuroprotective effects in various NDs and other neurological disorders both in vitro and in vivo. CBD has gained attention as a promising drug candidate for the management of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, by inhibiting protein aggregation, free radicals, and neuroinflammation. In parallel, CBD has shown positive results in other neurological disorders, such as epilepsy, depression, schizophrenia, and anxiety, as well as adjuvant treatment with existing standard therapeutic agents. Hence, the present review focuses on exploring the possible molecular mechanisms in controlling various neurological disorders as well as the clinical applications of CBD in NDs including epilepsy, depression and anxiety. In this way, the current review will serve as a standalone reference for the researchers working in this area.

Unveiling anti-diabetic potential of new thiazole-sulfonamide derivatives: Design, synthesis, in vitro bio-evaluation targeting DPP-4, α-glucosidase, and α-amylase with in-silico ADMET and docking simulation.

Diabetes mellitus type 2 (T2DM) can be managed by targeting dipeptidyl peptidase-4 (DPP-4), an enzyme that breaks down and deactivates peptides such as GIP and GLP-1. In this context, a new series of 2-(2-substituted hydrazineyl)thiazole derivatives 4, 5, 6, 8, 10, and 11 conjugated with the 2-hydroxy-5-(pyrrolidin-1-ylsulfonyl)benzylidene fragment were designed and synthesized. The virtual screening of the designed derivatives inside DPP-4 demonstrated good to moderate activity, with binding affinity ranging from -6.86 to -5.36 kcal/mol compared to Sitagliptin (S=-5.58 kcal/mol). These results encourage us to evaluate DPP-4 using in-vitro fluorescence-based assay. The in-vitro results exhibited inhibitory percentage (IP) values ranging from 40.66 to 75.62 % in comparison to Sitagliptin (IP=63.14 %) at 100 µM. Subsequently, the IC50 values were determined, and the 5-aryl thiazole derivatives 10 and 11 revealed strong potent IC50 values 2.75 ± 0.27 and 2.51 ± 0.27 µM, respectively, compared to Sitagliptin (3.32 ± 0.22 µM). The SAR study exhibited the importance of the substituents on the thiazole scaffold, especially with the hydrophobic fragment at C5 of the thiazole, which has a role in the activity. Compounds 10 and 11 were further assessed toward α-glucosidase and α-amylase enzymes and give promising results. Compound 10 showed good activity against α-glucosidase with IC50 value of 3.02 ± 0.23 µM compared to Acarbose 3.05 ± 0.22 µM and (11 = 3.34 ± 0.10 µM). On the other hand, for α-amylase, compound 11 was found to be most effective with IC50 value of 2.91 ± 0.23 µM compared to compound 10 = 3.30 ± 0.16 µM and Acarbose (2.99 ± 0.21 µM) indicating that these derivatives could reduce glucose by more than one target. The most active derivatives 10 and 11 attracted great interest as candidates for oral bioavailability and safe toxicity profiles compared to positive controls. The in-silico docking simulation was performed to understand the binding interactions inside the DPP-4, α-glucosidase, and α-amylase pockets, and it was found to be promising antidiabetic agents through a number of interactions.

Exploring Ubiquitin-specific proteases as therapeutic targets in Glioblastoma.

Glioblastoma (GB) remains a formidable challenge and requires new treatment strategies. The vital part of the Ubiquitin-proteasome system (UPS) in cellular regulation has positioned it as a potentially crucial target in GB treatment, given its dysregulation oncolines. The Ubiquitin-specific proteases (USPs) in the UPS system were considered due to the garden role in the cellular processes associated with oncolines and their vital function in the apoptotic process, cell cycle regulation, and autophagy. The article provides a comprehensive summary of the evidence base for targeting USPs as potential factors for neoplasm treatment. The review considers the participation of the UPS system in the development, resulting in the importance of p53, Rb, and NF-κB, and evaluates specific goals for therapeutic administration using midnight proteasomal inhibitors and small molecule antagonists of E1 and E2 enzymes. Despite the slowed rate of drug creation, recent therapeutic discoveries based on USP system dynamics hold promise for specialized therapies. The review concludes with an analysis of future wanderers and the feasible effects of targeting USPs on personalized GB therapies, which can improve patient hydration in this current and unattractive therapeutic landscape. The manuscript emphasizes the possibility of USP oncogene therapy as a promising alternative treatment line for GB. It stresses the direct creation of research on the medical effectiveness of the approach.

Genus Berberis: A Comprehensive and Updated Review on Ethnobotanical Uses, Phytochemistry and Pharmacological Activities.

Genus Berberis is an excellent choice for research due to its history in traditional medicine, diverse pharmacological properties, and it has potential for drug discovery. This review presents information on the ethnobotany, pharmacological activities, and many phytochemicals identified from Berberis species. It examines the existing literature on the genus Berberis, drawn from online databases, including PubMed, Web of Science, Science Direct, Elsevier, and Google Scholar, etc encompassing the data from 1960 to 2023. This review focuses on the structural details of reported phytochemicals of Berberis species and pharmacological actions. Different extraction techniques were evaluated for extracts preparation. According to literature review, phytochemical analysis exhibited the presence of alkaloids, flavonoids, and phenolic compounds. A major bioactive alkaloid, berberine exhibits its main role in treatment of many gastric, infectious, and chronic disorders. This literature indicates that Berberis genus exhibits a variety of biological activities, i.e anti-inflammatory, cytotoxic, hepatoprotective, antimicrobial, antidiabetic and antioxidant activities and utilization of these effects in the treatment and management of various diseases, like diabetes, microbial infections, inflammation, liver disorders, and cancer. However, conventional medicines, validation of traditional uses, and in-depth phytochemical analysis are areas of research in genus Berberis.

Non-Enzymatic Glucose Sensors Composed of Polyaniline Nanofibers with High Electrochemical Performance.

The measurement of glucose concentration is a fundamental daily care for diabetes patients, and therefore, its detection with accuracy is of prime importance in the field of health care. In this study, the fabrication of an electrochemical sensor for glucose sensing was successfully designed. The electrode material was fabricated using polyaniline and systematically characterized using scanning electron microscopy, high-resolution transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and UV-visible spectroscopy. The polyaniline nanofiber-modified electrode showed excellent detection ability for glucose with a linear range of 10 µM to 1 mM and a detection limit of 10.6 µM. The stability of the same electrode was tested for 7 days. The electrode shows high sensitivity for glucose detection in the presence of interferences. The polyaniline-modified electrode does not affect the presence of interferences and has a low detection limit. It is also cost-effective and does not require complex sample preparation steps. This makes it a potential tool for glucose detection in pharmacy and medical diagnostics.

The link between Alzheimer's disease and stroke: A detrimental synergism.

Being age-related disorders, both Alzheimer's disease (AD) and stroke share multiple risk factors, such as hypertension, smoking, diabetes, and apolipoprotein E (APOE) Ɛ4 genotype, and coexist in patients. Accumulation of amyloid-ß plaques and neurofibrillary tangled impair cognitive potential, leading to AD. Blocked blood flow in the neuronal tissues, causes neurodegeneration and cell death in stroke. AD is commonly characterized by cerebral amyloid angiopathy, which significantly elevates the risk of hemorrhagic stroke. Patients with AD and stroke have been both reported to exhibit greater cognitive impairment, followed by multiple pathophysiological mechanisms shared between the two. The manuscript aims to elucidate the relationship between AD and stroke, as well as the common pathways and risk factors while understanding the preventive therapies that might limit the negative impacts of this correlation, with diagnostic modalities and current AD treatments. The authors provide a comprehensive review of the link and aid the healthcare professionals to identify suitable targets and risk factors, that may retard cognitive decline and neurodegeneration in patients. However, more intricate research is required in this regard and an interdisciplinary approach that would target both the vascular and neurodegenerative factors would improve the quality of life in AD patients.

From diagnosis to therapy: The critical role of lncRNAs in hepatoblastoma.

According to findings, long non-coding RNAs (lncRNAs) serves an integral part in growth and development of a variety of human malignancies, including Hepatoblastoma (HB). HB is a rare kind of carcinoma of the liver that mostly affects kids and babies under the age of three. Its manifestations include digestive swelling, abdominal discomfort, and losing weight. This thorough investigation digs into the many roles that lncRNAs serve in HB, giving views into their varied activities as well as possible therapeutic consequences. The function of lncRNAs in HB cell proliferation, apoptosis, migratory and penetrating capacities, epithelial-mesenchymal transition, and therapy tolerance is discussed. Various lncRNA regulatory roles are investigated in depth, yielding information on their effect on essential cell processes such as angiogenesis, apoptosis, immunity, and growth. Circulating lncRNAs are currently acknowledged as potential indications for the initial stages of identification of cancer, with the ability to diagnose as well as forecast. In addition to their diagnostic utility, lncRNAs provide curative opportunities as locations and actors, contributing to the expanding landscape of cancer research. Several HB-linked lncRNAs have been demonstrated to exhibit abnormal expression and are involved in tumor-like characteristics via DNA, RNA, or protein binding or encoding short peptides. As a result, a better knowledge of lncRNA instability might bring fresh perspectives into HB etiology as well as innovative strategies for HB early diagnosis and therapy. We describe the abnormalities of lncRNA expression in HB and their tumor-suppressive or carcinogenic activities during HB carcinogenesis in this study. Furthermore, we explore lncRNAs' diagnostic and therapeutic possibilities in HB.

Discovery of new anti-diabetic potential agents based on paracetamol incorporating sulfa-drugs: Design, synthesis, α-amylase, and α-glucosidase inhibitors with molecular docking simulation.

Uncontrolled diabetes can lead to hyperglycemia, which causes neuropathy, heart attacks, retinopathy, and nervous system damage over time, therefore, controlling hyperglycemia using potential drug target inhibitors is a promising strategy. This work focused on synthesizing new derivatives via the diazo group, using a hybridization strategy involving two approved drugs, paracetamol and several sulfonamides. The newly designed diazo-paracetamols 5-12 were fully characterized and then screened for in vitro α-amylase and α-glucosidase activities and exhibited inhibitory percentages (IP) = 92.5-96.5 % and 91.0-95.7 % compared to Acarbose IP = 96.5 and 95.8 %, respectively at 100 µg/mL. The IC50 values of the synthesized derivatives were evaluated against α-amylase and α-glucosidase enzymes, and the results demonstrated moderate to potent activity. Among the tested diazo-paracetamols, compound 11 was found to have the highest potency activity against α-amylase with IC50 value of 0.98 ± 0.015 µM compared to Acarbose IC50 = 0.43 ± 0.009 µM, followed by compound 10 (IC50 = 1.55 ± 0.022 µM) and compound 9 (IC50 = 1.59 ± 0.023 µM). On the other hand, for α-glucosidase, compound 10 with pyrimidine moiety demonstrated the highest inhibitory activity with IC50 = 1.39 ± 0.021 µM relative to Acarbose IC50 = 1.24 ± 0.029 µM and the order of the most active derivatives was 10 > 9 (IC50 = 2.95 ± 0.046 µM) > 11 (IC50 = 5.13 ± 0.082 µM). SAR analysis confirmed that the presence of 4,5-dimethyl-isoxazole or pyrimidine nucleus attached to the sulfonyl group is important for activity. Finally, the docking simulation was achieved to determine the mode of binding interactions for the most active derivatives in the enzyme's active site.

Innovation of 6-sulfonamide-2H-chromene derivatives as antidiabetic agents targeting α-amylase, α-glycosidase, and PPAR-γ inhibitors with in silico molecular docking simulation.

A new series of 2-imino or 2-oxo-2H-chromene-6-sulfonamide derivatives 2-9 with potential anti-diabetic activity were designed and synthesized. The new 6-sulfonamide chromenes were synthesized by reacting 3-formyl-4-hydroxybenzenesulfonyl chloride with activated methylene derivatives in the presence of ammonium acetate as a catalyst. The structure of the products was confirmed by spectroscopic analysis. All the designed derivatives 2-9 were evaluated for their activity against α-amylase and exhibited inhibitory percentage values higher than 93% at 100 µg mL-1. Additionally, the IC50 values represented a variable degree of activity with two derivatives 2 and 9 exhibiting the most promising derivative results with IC50 values of 1.76 ± 0.01 and 1.08 ± 0.02 µM, respectively, compared to Acarbose (IC50 = 0.43 ± 0.01 µM). Additionally, these derivatives showed potency against the α-glucosidase enzyme with IC50 values of 0.548 ± 0.02 and 2.44 ± 0.09 µg mL-1, compared to Acarbose (0.604 ± 0.02 µg mL-1). Moreover, the in vitro PPAR-γ transactivation assay revealed that chromene-6-sulfonamide derivatives 2 and 9 exhibited potential PPAR-γ activity with IC50 values of 3.152 ± 0.03 and 3.706 ± 0.32 µg mL-1, respectively, compared to Pioglitazone (4.884 ± 0.29 µg mL-1). This indicates that these derivatives have insulin sensitivity and glucose metabolism activity. The in silico ADMET prediction showed that these derivatives have an acceptable range of oral bioavailability, drug-likeness, and a safe toxicity profile, including being non-cytotoxic, non-mutagenic, non-immunotoxic, and non-carcinogenic. Finally, computational docking analysis demonstrated the ability of these derivatives to interact with α-amylase, α-glucosidase, and PPAR-γ enzymes, with confirmed successful placement due to good binding energy values and various interactions within the pocket.

Discovery of novel 6-(piperidin-1-ylsulfonyl)-2H-chromenes targeting α-glucosidase, α-amylase, and PPAR-γ: Design, synthesis, virtual screening, and anti-diabetic activity for type 2 diabetes mellitus.

A new series of 2H-chromene-based sulfonamide derivatives 3-12 has been synthesized and characterized using different spectroscopic techniques. The synthesized 2H-chromenes were synthesized by reacting activated methylene with 5-(piperidin-1-ylsulfonyl)salicylaldehyde through one-step condensation followed by intramolecular cyclization. Virtual screening of the designed molecules on α-glucosidase enzymes (PDB: 3W37 and 3A4A) exhibited good binding affinity suggesting that these derivatives may be potential α-glucosidase inhibitors. In-vitro α-glucosidase activity was conducted firstly at 100 µg/mL, and the results demonstrated good inhibitory potency with values ranging from 90.6% to 96.3% compared to IP = 95.8% for Acarbose. Furthermore, the IC50 values were determined, and the designed derivatives exhibited inhibitory potency less than 11 µg/mL. Surprisingly, two chromene derivatives 6 and 10 showed the highest potency with IC50 values of 0.975 ± 0.04 and 0.584 ± 0.02 µg/mL, respectively, compared to Acarbose (IC50 = 0.805 ± 0.03 µg/mL). Moreover, our work was extended to evaluate the in-vitro α-amylase and PPAR-γ activity as additional targets for diabetic activity. The results exhibited moderate activity on α-amylase and potency as PPAR-γ agonist making it a multiplet antidiabetic target. The most active 2H-chromenes 6 and 10 exhibited significant activity to PPAR-γ with IC50 values of 3.453 ± 0.14 and 4.653 ± 0.04 µg/mL compared to Pioglitazone (IC50 = 4.884±0.29 µg/mL) indicating that these derivatives improve insulin sensitivity by stimulating the production of small insulin-sensitive adipocytes. In-silico ADME profile analysis indicated compliance with Lipinski's and Veber's rules with excellent oral bioavailability properties. Finally, the docking simulation was conducted to explain the expected binding mode and binding affinity.

Cananga odorata (Ylang-Ylang) Essential Oil Containing Nanoemulgel for the Topical Treatment of Scalp Psoriasis and Dandruff.

This research aimed to evaluate the efficacy of a nanoemulgel (NE) containing Cananga odorata (Ylang-Ylang) oil for managing scalp psoriasis and dandruff through various assessments. The study involved phytochemical screening, characterization, stability testing, in vivo performance evaluation, dermatokinetic analysis, central composite rotatable design (CCRD) optimization, in vitro release profiling, and antioxidant and antimicrobial activity assessment of the NE. The NE exhibited excellent stability and maintained physical parameters over a three-month period. In vivo studies showed no skin irritation, maintenance of skin pH (4.55 to 5.08), and improvement in skin hydration (18.09 to 41.28 AU) and sebum content (26.75 to 5.67 mg/cm2). Dermatokinetic analysis revealed higher skin retention of C. odorata in the NE (epidermis: 71.266 µg/cm2, dermis: 60.179 µg/cm2) compared to conventional formulations. CCRD optimization yielded NE formulations with the desired particle size (195.64 nm), entrapment efficiency (85.51%), and zeta potential (-20.59 mV). In vitro release studies indicated sustained release behavior, and antioxidant and antimicrobial properties were observed. This study demonstrates the stability, skin-friendliness, therapeutic benefits, and controlled release properties of the NE. The NE presents a promising option for various topical applications in treating bacterial and fungal diseases, potentially enhancing drug delivery and treatment outcomes in pharmaceuticals and cosmetics.