Current research trends of 1,2,4-triazole derivatives biological activity (literature review)

Traditional Chinese medicine (TCM) has sparked the public's attention for its potential in new drug development and its holistic view toward health, which is totally different from the reductionistic science of modern medicine. Although many scholars try to connect TCM with precision medicine or apply new methods and technology to integrate TCM with modern medicine, the misunderstandings and gap between TCM and modern medicine limit the development of evidence-based TCM. Traditional Chinese medicine is actually a medical science encompassing not only medicine but also philosophy and art in direct contrast to molecular-based modern medicine. As more and more multidisciplinary studies are being published, finding ways to integrate TCM with modern or precision medicine through artificial intelligence, new study design and technology may become a critical issue. This article aims to briefly review the unique philosophy of TCM and its conflicts with modern medicine, with a focus on the potential integration of TCM and modern medicine. We also provide insight for the key attributes of TCM and the associated investigation with Western research approaches.

Europe to boost development of new antimicrobial drugs

Pyridine and its derivatives are six-membered aromatic rings containing nitrogen, which are abundant in nature and indispensable in studying heterocyclic chemistry. They constitute significant chemical substances with numerous applications. The application of pyridine derivatives by incorporating metals in modern medicine is growing in relevance. Due to their convenient parallelization and various testing capabilities in the chemical domain, pyridine derivatives have attracted increased interest in the treatment of various disease states. This review aims to systematically evaluate and highlight the recent advancements in the synthesis (conventional, synthetic, and green approach) and biological activities of metal-based pyridine derivatives, including antioxidant, antimicrobial, and antitumor activities, while identifying promising candidates for further drug development. By consolidating all this knowledge underlying their biological effects, this review aims to pave the way for future research endeavors and encourage the exploration of pyridine derivatives as viable therapeutic agents across a diverse array of medical applications.

Regarding scientific research, Imidazo[1,2-a] pyridine derivatives are constantly being developed due to the scaffold's intriguing chemical structure and varied biological activity. They are distinctive organic nitrogen-bridged heterocyclic compounds that have several uses in medicines, organometallics and natural products. It has become a vital tool for medicinal chemists. In order to gather scientific information on Imidazo[1,2-a] pyridines derivative, Google, PubMed, Scopus, Google Scholar, and other databases were searched. In the current study, the medicinal value and therapeutic effect of Imidazo[1,2-a] pyridines were investigated using above mentioned databases. The current study analyzed the detailed pharmacological activities of Imidazo[1,2-a] pyridine analogs through literature from diverse scientific research works. Due to its wide range of biological activities, including antiulcer, anticonvulsant, antiprotozoal, anthelmintic, antiepileptic, antifungal, antibacterial, analgesic, antiviral, anticancer, anti-inflammatory, antituberculosis, and antitumor properties, imidazopyridine is one of the most significant structural skeletons in the field of natural and pharmaceutical products. An imidazopyridine scaffold serves as the basis for a number of therapeutically utilized medications, including zolpidem, alpidem, olprinone, zolimidine, and necopidem. This comprehensive study covers the period of the last five years, and it sheds light on the developments and emerging pharmacological actions of Imidazo[1,2-a] pyridines. Additionally, the structure-activity relationship and molecular docking studies are carefully documented throughout the paper, providing medicinal chemists with a clear picture for developing new drugs.

A review on antioxidant potential of bioactive heterocycle benzofuran: Natural and synthetic derivatives.

Introduction. In modern conditions, where military conflicts are accompanied by significant psychological and physical stress on participants, the development of effective antiepileptic drugs has become one of the key challenges in medicine. This issue is particularly relevant due to the increasing number of cases of traumatic brain injuries, concussions, and other stress-related damages that can provoke convulsive states. In this context, derivatives of 1,2,4-triazole, which possess a broad spectrum of biological activity, including anticonvulsant effects, appear promising for the creation of new pharmaceutical agents capable of meeting the needs of military medicine. The purpose of the study was to investigate the biological activity of 2-[5-(furan-2-yl)-4-phenyl-4H-1,2,4-triazol-3-ylthio]-1-(4-chlorophenyl)ethanone using computer-based predictive methods. This approach allows to determine the presence of new types of activity, which could expand scientific research pathways and establish a promising direction for further testing of this molecule. Materials and methods. Molecular docking was performed using Autodock 4.2.6. For screening, the crystallographic structures of GABAA receptors –“4COF,” “6D6T,” and “6X3U” - obtained from the RCSB Protein Data Bank were used. Visualization of the results was conducted using Schrödinger Release 2018-1: Schrödinger, LLC, New York, NY, 2018. The grid parameters for binding were 30 Å × 30 Å × 30 Å, and the grid center coordinates were: 4COF (7 Å × 12 Å × 132 Å), 6D6T (119 Å × 181 Å × 126 Å), 6X3U (137 Å × 108 Å × 142 Å), which provided a sufficiently large space to encompass the receptor center. The ADME evaluation was performed using the free SwissADME tool, which is widely used in medicinal chemistry for analyzing pharmacokinetics, bioavailability, and interactions of small molecules with enzymes. This service considers six physicochemical characteristics: lipophilicity, size, polarity, solubility, flexibility and saturation. Each of these characteristics has its own physicochemical range, which is visualized as a pink zone on the radar plot. For a molecule to be considered drug-like, its radar profile must be entirely within this zone. Results. The study of the interaction of the selected compound with GABAA receptors (4COF, 6D6T, 6X3U) demonstrated its ability to stably bind to the active sites of the receptors, as evidenced by binding energies ranging from –6.119 to –8.559 kcal/mol. The main interactions include hydrophobic contacts, hydrogen bonds, and electrostatic interactions, indicating the compound's potential to modulate receptor activity. The high binding energy values, particularly for the 6X3U structure, suggest the possibility of effectively influencing neuronal excitability, which is promising for the development of antiepileptic agents. The obtained results confirm that the selected compound has potential for further research as a candidate for the development of new pharmaceutical drugs. Conclusions. The pharmacokinetic analysis demonstrated favourable bioavailability characteristics of the compound, including optimal lipophilicity, solubility, and molecular size, in accordance with the parameters typical for pharmaceutical drugs. This enhances the prospects for further investigation of the compound in experimental epilepsy models and for the development of new anticonvulsant drugs based on it. The use of computer modelling significantly accelerates the selection of promising compounds, reduces drug development costs, and contributes to the creation of more effective medications for military personnel in the future.

Lungworts (members of genus Pulmonaria), especially Pulmonaria officinalis, have been used as medicinal plants in folk and traditional medicine. The potential biological activities of lungworts, such as antioxidant, anti-inflammatory, anti-neurodegenerative, skin whitening, anticoagulant, antibacterial, anti-anemic, anticonvulsant, and wound-healing properties, have been observed in different studies. More than 90 phytochemicals belonging to pharmacologically active phytochemical classes have been reported for lungworts, which can be considered as one of the important contributors to the biological properties along with micronutrients. However, safety studies and clinical trials are missing for lungworts to establish most of their potential biological properties. Similarly, in vivo studies are lacking for anti-inflammatory and anti-neurodegenerative disorders and more in vivo studies are required to strengthen the knowledge of their antioxidant, anticoagulant, and anti-convulsant properties. A comprehensive compilation of the phytochemicals and biological properties of lungworts is also lacking in the literature, which can provide future direction for further pharmacological research. Hence, an attempt has been made in this study to compile the phytochemicals and biological properties to not only provide the resources for the design of further research to develop the pharmacological application of lungworts, but also to highlight the gaps and provide suggestions for future development.

Although the antiallergic properties of compounds such as CAPE, Melatonin, Curcumin, and Vitamin C have been poorly discussed by experimental studies, the antiallergic properties of these famous molecules have never been discussed with calculations. The histamine-1 receptor (H1R) belongs to the family of rhodopsin-like G-protein-coupled receptors expressed in cells that mediate allergies and other pathophysiological diseases. In this study, pharmacological activities of FDA-approved second generation H1 antihistamines (Levocetirizine, desloratadine and fexofenadine) and molecules such as CAPE, Melatonin, Curcumin, Vitamin C, ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) profiles, density functional theory (DFT), molecular docking, biological targets and activities were compared by calculating. Since drug development is an extremely risky, costly and time-consuming process, the data obtained in this study will facilitate and guide future studies. It will also enable researchers to focus on the most promising compounds, providing an effective design strategy. Their pharmacological activity was carried out using computer-based computational techniques including DFT, molecular docking, ADMET analysis, biological targeting, and activity methods. The best binding sites of Desloratadine, Levocetirizine, Fexofenadine, CAPE, Quercetin, Melatonin, curcumin, Vitamin C ligands to Desmoglein 1, Human Histamine H1 receptor, IgE and IL13 protons were determined by molecular docking method and binding energy and interaction states were analyzed. Fexofenadine and Quercetin ligand showed the most effective binding affinity. Melatonin had the best Caco-2 permeability PPB values of Quercetin, CAPE and Curcumin were at optimal levels. On the OATP1B1 and OATP1B3 of curcumin and CAPE, Quercetin was found to have strong inhibition effects on BCRP. Melatonin and CAPE were found to have the highest inhibition values on CYP1A2, while CAPE had the highest inhibition values on CYP2C19 and CYP2C9. Vitamin C and Quercetin were found to be safer in terms of cardiac toxicity and mutagenic risks, while Desloratadine and Levocetirizine carried high risks of neurotoxicity and hematotoxicity, while CAPE was noted for its high enzyme inhibitory activities and low toxicity profiles, while the hERG blockade, DILI, and cytotoxicity values of other compounds pointed to various safety concerns. This study demonstrated the potential of machine learning methods in understanding and discovering H1 receptor blockers. The results obtained provide important clues in the development of important strategies in the clinical use of H1 receptor blockers. In the light of these data, CAPE and Quercetin are remarkable molecules.

Molecular docking methods were applied to simulate the coupling of a set of nineteen acyl homoserine lactone analogs into the binding site of the transcriptional receptor LasR. The best pose of each ligand was explored and a qualitative analysis of the possible interactions present in the complex was performed. From the results of the protein-ligand complex analysis, it was found that residues Tyr-64 and Tyr-47 are involved in important interactions, which mainly determine the antagonistic activity of the AHL analogues considered for this study. The effect of different substituents on the aromatic ring, the common structure to all ligands, was also evaluated focusing on how the interaction with the two previously mentioned tyrosine residues was affected. Electrostatic potential map calculations based on the electron density and the van der Waals radii were performed on all ligands to graphically aid in the explanation of the variation of charge density on their structures when the substituent on the aromatic ring is changed through the elements of the halogen group series. A quantitative approach was also considered and for that purpose the ONIOM method was performed to estimate the energy change in the different ligand-receptor complex regions. Those energy values were tested for their relationship with the corresponding IC50 in order to establish if there is any correlation between energy changes in the selected regions and the biological activity. The results obtained using the two approaches may contribute to the field of quorum sensing active molecules; the docking analysis revealed the role of some binding site residues involved in the formation of a halogen bridge with ligands. These interactions have been demonstrated to be responsible for the interruption of the signal propagation needed for the quorum sensing circuit. Using the other approach, the structure-activity relationship (SAR) analysis, it was possible to establish which structural characteristics and chemical requirements are necessary to classify a compound as a possible agonist or antagonist against the LasR binding site.

An insight into the biological activity and structure-based drug design attributes of sulfonylpiperazine derivatives

The rising interest in natural products for their biomedical applications marks an exciting era in modern medicine. Natural products, derived from plants and microorganisms, have been the cornerstone of traditional medicine for centuries. Their unique chemical diversity and biological activities offer vast potential for developing novel therapeutic agents. This letter highlights the critical role of natural products in revitalizing healthcare and their promising future in modern medicine. Natural products have historically provided effective treatments for various diseases, with drugs like paclitaxel and artemisinin exemplifying their impact. The rise of antimicrobial resistance has renewed interest in natural products as sources of new antibiotics. Additionally, natural compounds with anti-inflammatory and antioxidant properties, such as curcumin, show significant promise in managing chronic diseases. Technological advancements have accelerated the discovery and development of natural productbased drugs, though challenges like sustainable sourcing and regulatory hurdles remain. Addressing these challenges and fostering global collaboration can unlock the full potential of natural products and drive healthcare innovation.

DTI-BGCGCN: A novel bipartite graph-based cluster graph convolutional network for drug-target interaction prediction in modern and traditional chinese medicine.

Chemical diversity, biological activities and Traditional uses of and important Chinese herb Sophora

NAD(P)H quinone oxidoreductase 1 (NQO1) plays a critical role in catalyzing the reduction of quinones, thereby exerting both chemical protection and biological activation. The expression level of NQO1 in various tumor cells, especially glioma, lung cancer, colon cancer and breast cancer cells, is higher than that in normal tissues, the detection of NQO1 activity is important to understand tumor development mechanisms. Herein, a near-infrared (NIR) fluorescent probe DDANQ was rationally designed and synthesized through a systematic approach. The optical properties and enzyme selectivity of DDANQ were also elucidated by chemical calculation and molecular docking methods. The results showed that DDANQ showed excellent stability, and displayed good selectivity and sensitivity toward NQO1. DDANQ could be used as a molecular tool to elucidate the activity and function of NQO1 in physiological and pathological processes, which could provide valuable insights for tumor diagnosis and treatment.

Inflammation is a local reaction in vascular tissue characterized by several symptoms, e.g., swelling, redness, and pain. Indonesia is one of the countries with high biodiversity, including traditional medicinal plants. Artocarpus altilis is one the plants that is widely used to treat inflammation. There is limited information on biological activity of A. altilis.This study was performed to evaluate anti-inflammatory properties of A. altilis detached and attached leaves in Wistar male rats. A. altilis was extracted using soxhlet method at 67.4 0C with methanol solvent. Inflammation was induced by the administration of carrageenan to the rats paw. Subsequently, the extract of A. altilis were orally administered. The edema were measured using plethysmometer for 6 hours. We found that there were differences in anti-inflammatory activity between detached and attached leaves. The inhibition of edema in attached leaves were 50% and 53.33% for the concentration of 50 mg and 100 mg, respectively. The greater inhibiton was observed in the detached leaves, with 73.33% and 76.67% inhibition, for the concentration of 50 mg and 100 mg, respectively. Nevertheless, the inhibition percentage was still below diclofenac sodium as a positive control (83.33%). In conclusion, A. altilis leaves extracts showed good anti-inflammatory properties and has the potential for development of anti-inflammatory drug. Keywords: Artocarpus altilis, carageenan, inflammation, edema