Potential Pharmacophore Research Articles

Discovery of Dual ROCK1/2 Inhibitors from Nocardiopsis sp. under Metal Stress.

Rho-associated protein kinase (ROCK) inhibitors are promising therapeutic agents for reducing elevated intraocular pressure in patients with glaucoma. We explored new ROCK inhibitors derived from bioactive metabolites produced by microbes, specifically cryptic metabolites from Nocardiopsis sp. MCY7, using a liquid chromatography-mass spectrometry-based chemical analysis approach integrated with metal stress-driven isolation. This strategy led to the identification of two previously undescribed linear peptides, nocarnickelamides A and B (1 and 2), and an unreported cittilin derivative, cittilin C (3). The planar structures of 1-3 were elucidated using UV spectroscopy, high-resolution mass spectrometry, and nuclear magnetic resonance. The absolute configurations of 1 and 2 were assigned using the advanced Marfey's method. Biological assays demonstrated that nocarnickelamides (1 and 2) exhibited dual inhibitory activity against ROCK1 (IC50 29.8 and 14.9 μM, respectively) and ROCK2 (IC50 27.0 and 21.9 μM, respectively), with molecular simulations suggesting binding to the ATP-binding site. In human trabecular meshwork cells, 2 significantly inhibited the activation of ROCK-regulated cytoskeletal contraction markers such as the myosin light chain. Nocarnickelamide B (2) is a novel dual ROCK1/2 inhibitor and a potential pharmacophore for designing new therapeutic agents to reduce intraocular pressure in glaucoma.

Experimentation of Heterocycles (2013-22) as Potent Pharmacophores in Drug Design of Multiple Sclerosis.

Multiple sclerosis (MS) is a demyelinating disease in which the insulating cover (myelin sheath) of the brain and spinal cord is damaged. Demyelination results in a decreased signal transmission in the nervous system. Symptoms include double vision, muscle weakness, and difficulty with coordination. Genetic and viral infections have been proposed as plausible factors responsible for MS. Although there is no cure for MS, treatment prevents future attacks. At present, chemotherapy and monoclonal antibodies are the available treatments for MS. Heterocyclic compounds are currently being tested clinically for their efficacy. Some heterocyclic scaffolds have been found to be promising for the treatment of MS. In view of this, research has been conducted towards the design and discovery of chemical agents for MS. Hence, the literature relevant to drug design for MS in the last decade has been collated and described comprehensively so that it would be helpful for efficient drug design for MS in the future. Additionally, through the structure-activity relationship, the importance of crucial structural features was emphasized. The classification was primarily based on the type of heterocycle.

VIRTUAL SCREENING AND PREDICTION OF ADME PERAMETERS OF A SERIES OF 5-ARYLIDENE SUBSTITUTED DERIVATIVES OF RHODANINE WITH BENZOTHIAZOLE MOIETY IN THE MOLECULES

The knowledge of the ADME profile of the active substance’s molecules is important in the development of new drugs. Before starting the synthesis, it is advisable to determine the value of the compounds for medicinal chemistry and to predict their bio- and synthetic availability. For the assessment of the drug-like properties of the molecules, it is necessary to determine their physicochemical and pharmacokinetic properties. The 2-thioxothiazolidin-4-one (rhodanine) derivatives are interesting in pharmacological terms, as their diverse activity is influenced by the 5-arylidene moiety. It is known that they have antiviral, antidiabetic, anticonvulsant and other types of biological activity. In order to find effective ligands that have affinity for several biotargets, it is advisable to combine the so-called privileged structures in one molecule. One of such molecules with a wide range of biological effects (antitumor, antiviral, antituberculosis and other) is benzothiazole. A considerable number of possible ways for the structure modification of these heterocycles prompted us to study them in depth. The preliminary studies allow us to state that the combination of 5-arylidene-substituted 4-thiazolidine scaffold with a benzothiazole moiety is a viable approach to create drug-like molecules. In continuation of our previous studies, we decided to use an open access in silico tool to calculate the molecular descriptors of the studied compounds in order to predict their behaviour inside the human body, and to thoroughly study the most promising ones in vitro and in vivo in the future. The aim of the research. On the basis of the molecular structure of differently substituted 5-arylidene thiazolidine derivatives with a benzothiazole moiety at the 3-position of the basic heterocycle, perform in silico prediction of their ADME parameters. Materials and methods. On the basis of the pharmacological potential of the lead compound (N-(4-oxo-2-thioxothiazolidin-3-yl)-2-(2-oxobenzo[d]thiazol-3(2H)-yl)acetamide), 17 differently substituted 5-arylidene derivatives were selected for virtual screening. To determine the physicochemical and pharmacokinetic parameters of the molecules, their drug-like properties and suitability for medicinal chemistry, we used the SwissADME web service, which is in open access. Research results. We have studied the effect of aryl substituents at position 5 of the rhodanine cycle on the peroral availability of molecules, predicted the absorption, distribution, metabolism and excretion of compounds. The obtained prognosis data indicate the viability of the search for promising compounds with optimal physicochemical and pharmacokinetic parameters for medicinal chemistry among rhodanine derivatives with a benzothiazole moiety in the molecules. All the investigated derivatives are characterised by sufficient drug-like properties with moderate bioavailability and easy synthesis, and compound 8 is predicted to have the best ADME profile. Conclusions. The in silico prediction results outline a plan of further actions for the targeted synthesis of compounds and experimental confirmation of the data obtained. To optimise the ADME profile, we plan to carry out structural modification of the compounds. A promising direction we consider is the modification of the 5-arylidene moiety by introducing potential pharmacophore groups. The search for pharmacologically active compounds among rhodanine derivatives with a benzothiazole moiety is ongoing.

Identification of Novel Potential Herbal Drug Targets against Beta-Catenin in the Treatment of Oral Squamous Cell Carcinoma.

The study aims to identify potential pharmacophore models for targeting beta-catenin, a crucial protein involved in the development of oral squamous cell carcinoma (OSCC), using a combination of herbal compounds and computational approaches. Five natural compounds namely Quercetin, Lycopene, Ovatodiolide, Karsil, and Delphinidin were selected based on their reported activity against beta-catenin. Ligand characteristics were analyzed using SwissADME to evaluate drug-likeness, lipophilicity (logP), and bioavailability. The three-dimensional structure of beta-catenin was retrieved from the Protein Data Bank (PDB). Pharmacophore modeling was performed using Pharmagist software, followed by molecular docking using Swissdock to assess binding interactions and energies. Out of thousands of pharmacophore hits generated, 23 were selected based on drug-likeness properties. Molecular docking revealed that ZINC94512303, derived from the combination of the selected herbal compounds, exhibited the highest binding energy of -8.91 kcal/mol with beta-catenin, outperforming individual herbal compounds. This compound adhered to all drug-likeness rules and demonstrated optimal pharmacokinetic properties. The identified pharmacophore, ZINC94512303, shows promise as a therapeutic agent targeting beta-catenin in OSCC. The combination of computational drug design with herbal compounds offers a novel approach to enhance the efficacy of cancer treatment. Further pharmacokinetic and pharmacodynamic studies, along with in vitro and clinical evaluations, are recommended to validate the therapeutic potential of this compound.

Antioxidant, cytotoxic, anti-migratory, and pro-apoptotic effects of Bolanthus turcicus extracts on head and neck cancer cells.

Investigation of various plant extracts using in-vitro/in-vivo assays has emerged as a promising avenue for identifying potential pharmacophores that can be developed into therapeutic drugs. This study aims to assess the bioactive compounds and antioxidant capacity of the Bolanthus turcicus (B. turcicus) and to investigate the effects on head and neck cancer (HNC) cell lines. Methanol (MeOH), ethyl acetate (EA) and aqueous (Aq) extracts were prepared from B. turcicus, and the amount of total phenolic content (TPC) and total flavonoid content (TFC) in the extracts were analyzed by the Folin-Ciocalteu and Aluminum chloride method, respectively. In addition, the total antioxidant capacity and iron reducing potential of B. turcicus extracts were determined by the Phosphomolybdenum and Ferric ion reducing antioxidant power (FRAP) method. The effect of B. turcicus on HEp-2, SCC-90, SCC-9, FaDu HNC cell viability, motility, and cell-nuclear morphology was evaluated by MTT, scratch-wound healing assay, and Pllalloidin-DAPI staining, respectively. The effect of B. turcicus on the expression of CASP-3, BAX, and BCL-2 genes at the mRNA, protein, and intracellular level was evaluated by quantitative PCR (qPCR), western blot, and immunofluorescence staining. Moreover, Annexin V-FITC/PI, was used in flow cytometry to investigate the effect of B. turcicus on apoptosis. The MeOH extract exhibited the highest phenolic content, flavonoid content and antioxidant activity (p < 0.05 for all). HNC cells treated with extracts indicated delayed wound healing and decreased motility (p < 0.05 for all). Analysis of annexin V-PI staining indicated that the B. turcicus extracts induced apoptosis but not viability and necrosis in the HNC cell (p < 0.05 for all). Moreover, qPCR data regarding the apoptotic mechanism showed that the extracts could induce apoptosis by upregulation of pro-apoptotic CASP-3 and BAX genes and downregulation of anti-apoptotic BCL-2 gene (p < 0.05 for all). The expression of protein and intracellular levels of CASP-3 and BAX were increased, while the BCL-2 was decreased in cells treated with the extracts (p < 0.05 for all). In addition, diffuse pycnosis and DNA condensation in HNC cell nuclei, confirming apoptotic cell death (p < 0.05 for all). This study data indicated that B. turcicus extracts have antioxidant, cytotoxic, anti-migratory and pro-apoptotic activity. In conclusion, it has been shown that B. turcicus can be used as a potential therapeutic agent against HNC.

Deprotective Lossen rearrangement: a direct and general transformation of Nms-amides to unsymmetrical ureas.

Ureas stand out as potent pharmacophores in drug development, rendering them a prime focus for synthesis. Herein, we present an appealing entry point for urea synthesis from protected amines (Nms-amides) and relying on a Lossen-type rearrangement process as an elegant example of deprotective functionalisation. The method developed exhibits an exceptionally broad tolerance towards various protected amines, encompassing numerous drug derivatives, and delivers high reaction yields.

Inhibitory Potential of Benzo[a]phenazin-5-ol Derivatives Against C-Kit Kinase: Molecular Docking and Prediction of ADME/Drug-Likeness Properties

Background &amp; Objectives: C-Kit, a receptor tyrosine kinase involved in intracellular signaling, has a mutated form that significantly contributes to the development of certain cancers. This study aimed to evaluate a series of benzo[a]phenazin-5-ol-tethered tri- substituted methane derivatives as potential pharmacophores for inhibiting C-Kit kinase. Materials &amp; Methods: Benzo[a]phenazine-5-ol derivatives were sketched and converted into Mol2 files using Marvin software. Their three dimensional (3D) structures were generated and saved in PDB format. Molecular docking studies with the C-Kit kinase (PDB code 1t46) were performed using AutoDock 4.2. Additionally, the derivatives’ physicochemical properties, ADME characteristics, and drug-likeness parameters were assessed with the SwissADME online tool. Results: Molecular docking studies of benzo[a]phenazin-5-ol derivatives ( A-L) against C-kit kinase revealed that compounds A and C exhibited greater selectivity and stronger inhibitory effects than the reference drug, Sunitinib. Ligplot analysis demonstrated that compound A formed four hydrogen bonds with Arg791(A), Ile789(A), and His790(A), while compound C formed two hydrogen bonds with Ile571(A) and Ile789(A). ADME analysis indicated that all compounds, except C, D, and I, are potential P-gp substrates. Drug-likeness analysis showed one or two violations of Lipinski’s rule of five. Conclusion: In summary, molecular docking studies identified compounds A and C as promising lead candidates for inhibiting C-kit kinase, demonstrating superior binding to the active site compared to Sunitinib. ADME and drug-likeness analysis revealed that compound A is a potential P-gp substrate with one violation of Lipinski’s rule of five, making it the closest pharmacological match to Sunitinib and a strong candidate for further investigation.

Efficient synthesis, crystallographic study, antimicrobial activity and in silico studies of novel bioactive α-aminophosphonates based on pyridine moiety

This study articulates the synthesis, spectroscopic characterization, antimicrobial evaluation, theoretical calculations, and molecular docking analysis of a novel α-aminophosphonates derived from aminopyridine as potential antibacterial pharmacophore. The structures of all compounds was established using FTIR, 1H, 13C, 31P NMR spectroscopy. A single crystal of the studied compound 3g was selected for X-ray diffraction analysis, it crystallizes in the monoclinic crystal system with P 21/n space group. Theoretical studies based on density functional theory (DFT) at the B3LYP /6-31G (d, p) level of theory was utilized to investigate the stability and electronic properties electronic of the studied α-aminophosphonates. The ADME/toxicity analyzes carried out by Swiss ADME and OSIRIS software show that all synthesized molecules exhibited good pharmacokinetics, bioavailability and had no toxicity profile.

Molecular docking, pharmacokinetic profiling and toxicity studies of 2-substituted benzimidazole derivatives against breast cancer

The most prevalent malignancy among women is breast cancer, which had almost 1.3 million new cases in 2020. It is the second most common cancer in the world, followed by lung cancer. The survival rate would be 99% if the cancerous tumour was limited to the breast. If the cancer migrated to neighbouring lymph nodes, the survival percentage would be 85% and it would drop to 27% if it spread to distant regions. In fact, the most prevalent breast cancer subtype is that caused by excessive estrogen levels. The enhancement of pertinent treatment techniques depends on the estrogen receptors (ER) in both healthy and pathological conditions. There are two primary types of ER, ERα and ERβ, which are each encoded by a different gene. ER status is the most important indicator of breast cancer prediction. To develop novel therapeutics for breast cancer, 30 newly designed benzimidazole compounds targeting the ER were docked. Among them, a compound with a glide score of −9.293 was discovered to be the leading compound. ADME investigations provided additional validation of the docking results. The pyrazole fused benzimidazole nucleus is therefore suggested as a potential pharmacophore for the development of innovative anticancer treatment for breast cancer.

Development of Neuroprotective Agents for the Treatment of Alzheimer's Disease using Conjugates of Serotonin with Sesquiterpene Lactones.

Sesquiterpene lactones are secondary plant metabolites with a wide variety of biological activities. The process of lactone conjugation to other pharmacophores can increase the efficacy and specificity of the conjugated agent effect on molecular targets in various diseases, including brain pathologies. Derivatives of biogenic indoles, including neurotransmitter serotonin, are of considerable interest as potential pharmacophores. Most of these compounds have neurotropic activity and, therefore, can be used in the synthesis of new drugs with neuroprotective properties. The aim of this experimental synthesis was to generate potential treatment agents for Alzheimer's disease using serotonin conjugated with natural sesquiterpene lactones. Three novel compounds were obtained via the Michael reaction and used for biological testing. The obtained conjugates demonstrated complex neuroprotective activities. Serotonin conjugated to isoalantolactone exhibited strong antioxidant and mitoprotective activities. The agent was also found to inhibit β-site amyloid precursor protein cleaving enzyme 1 (BACE-1), prevent the aggregation of β-amyloid peptide 1-42, and protect SH-SY5Y neuroblastoma cells from neurotoxins such as glutamate and H2O2. In a transgenic animal model of Alzheimer's disease (5xFAD line), the conjugated agent restored declined cognitive functions and improved learning and memory. In conclusion, the obtained results indicate that serotonin conjugates to sesquiterpene lactones are promising agents for the treatment of symptoms associated with Alzheimer's disease.

Nitrogen-containing heterocyclic compounds: A ray of hope in depression?

Depression is not similar to daily mood fluctuations and temporary emotional responses to day-to-day activities. Depression is not a passing problem; it is an ongoing problem. It deals with different episodes consisting of several symptoms that last for at least 2 weeks. It can be seen for several weeks, months, or years. At its final stage, or can say, in its worst condition, it can lead to suicide. Antidepressants are used to inhibit the reuptake of the neurotransmitters by some selective receptors, which increase the concentration of specific neurotransmitters around the nerves in the brain. Drugs that are currently being used for the management of various types of depression include selective serotonin reuptake inhibitors, tricyclic antidepressants, atypical antidepressants, serotonin, noradrenaline reuptake inhibitors, etc. In this review, we have outlined different symptoms, causes, and recent advancements in nitrogen-containing heterocyclic drug candidates for the management of depression. This article highlights the various structural features along with the structure-activity relationship (SAR) of nitrogen-containing heterocyclics that play a key role in binding at target sites for potential antidepressant action. The in silico studies were carried out to determine the binding interactions of the target ligands with the receptor site to determine the potential role of substitution patterns at core pharmacophoric features. This article will help medicinal chemists, biochemists, and other interested researchers in identifying the potential pharmacophores as lead compounds for further development of new potent antidepressants.

Synthesis, antileishmanial, antimalarial evaluation and molecular docking study of some hydrazine-coupled pyrazole derivatives

Pyrazole-bearing compounds are known for their diverse pharmacological effects including potent antileishmanial and antimalarial activities. Herein, some hydrazine-coupled pyrazoles were successfully synthesized and their structures were verified by employing elemental microanalysis, FTIR, and 1H NMR techniques. The in vitro antileishmanial and in vivo antimalarial activities of the synthesized pyrazole derivatives (9–15) were evaluated against Leishmania aethiopica clinical isolate and Plasmodium berghei infected mice, respectively. The result revealed that compound 13 displayed superior antipromastigote activity (IC50 = 0.018) that was 174- and 2.6-fold more active than the standard drugs miltefosine (IC50 = 3.130) and amphotericin B deoxycholate (IC50 = 0.047). The molecular docking study conducted on Lm-PTR1, complexed with Trimethoprim was acquired from the Protein Data Bank (PDB ID:2bfm), justified the better antileishmanial activity of compound 13. Furthermore, the target compounds 14 and 15 elicited better inhibition effects against Plasmodium berghei with 70.2% and 90.4% suppression, respectively. In conclusion, the hydrazine-coupled pyrazole derivatives may be considered potential pharmacophores for the preparation of safe and effective antileishmanial and antimalarial agents.

Alternatives to β-Lactams as Agents for the Management of Dentoalveolar Abscess.

Dentoalveolar abscess are localized infections within the tooth or the surrounding alveolar bone, often resulting from untreated dental caries or dental trauma causing alveolar bone resorption or even loss. Serious consequences arising from the spread of a dental abscess can often lead to significant morbidity and mortality. The acute dentoalveolar abscess is a polymicrobial infection comprising strict anaerobes, such as anaerobic cocci i.e., Prevotella fusobacterium species, and facultative anaerobes i.e., Streptococci viridians and Streptococcus anginosus. Moreover, inappropriately managed dental infections can progress to severe submandibular space infections with associated serious complications, such as sepsis and airway obstruction. An audit of the Hull Royal Infirmary between 1999 and 2004 showed an increase in the number of patients presenting to oral and maxillofacial surgery services with dental sepsis. Thus, the scientific community is forced to focus on treatment strategies for the management of dentoalveolar abscess (DAA) and other related dental problems. The current treatment includes antibiotic therapy, including β-lactams and non-β- lactams drugs, but it leads to the development of resistant microorganisms due to improper and wide usage. Furthermore, the currently used β-lactam therapeutics is non-specific and easily hydrolyzed by the β-lactamase enzymes. Thus, the research focused on the non-β-lactams that can be the potential pharmacophore and helpful in the management of DAA, as the appropriate use and choice of antibiotics in dentistry plays an important role in antibiotic stewardship. The newer target for the choice is NLRP inflammasome, which is the major chemical mediator involved in dental problems. This review focused on pathogenesis and current therapeutics for the treatment of dentoalveolar abscesses.

Synthesis of dimeric 1,2-benzothiazine 1,1-dioxide scaffolds: molecular structures, Hirshfeld surface analysis, DFT and enzyme inhibition studies.

1,2-Benzothiazines are bioactive compounds with diverse pharmacological properties. We report here the synthesis of a series of dimers containing 1,2-benzothiazine scaffolds as potential pharmacophores. The characterization of compounds was done using analytical techniques such as FT-IR, 1H NMR, and elemental analyses. The molecular structures of the compounds (5-8) were confirmed by X-ray crystallography. The molecular interactions in compounds (5-8) were determined by Hirshfeld Surface Analysis (HSA). Density functional theory (DFT) investigations were carried out to calculate vibrational properties, NMR behaviour, dipole moments, molecular electrostatic potential (MEP), frontier molecular orbital (FMO), natural bonding orbital (NBO) analysis and global reactivity descriptors. The global reactivity descriptors indicated the charge transfer reactions and stabilized as follows: 8 > 7 > 6 > 5. In FMO analysis a substantial HOMO-LUMO gap, ranging from 4.43 to 5.12 eV, with high LUMO values was observed for all compounds, while the highest value for linear polarizability was found in compound 8. The in vitro and in silico studies confirm that compound 8 is more active toward AChE and BChE enzymes.

Photosubstitution and photoreduction of a diazido platinum(IV) anticancer complex.

The hyphenation of HPLC with its high separation ability and ICP-MS with its excellent sensitivity, allows the analysis of Pt drugs in biological samples at the low nanomolar concentration levels. On the other hand, LC-MS provides molecular structural confirmation for each species. Using a combination of these methods, we have investigated the speciation of the photoactive anticancer complex diazido Pt(IV) complex trans, trans, trans-[Pt(N3)2(OH)2(py)2] (FM-190) in aqueous solution and biofluids at single-digit nanomolar concentrations before and after irradiation. FM-190 displays high stability in human blood plasma in the dark at 37 °C. Interestingly, the polyhydroxido species [{PtIV(py)2(OH)4} + Na]+ and [{PtIV(py)2(N3)(OH)3} + Na]+ resulting from the replacement of azido ligands, as determined by LC-MS, were the major products after photoirradiation of FM-190 with blue light (463 nm). This finding suggests that such photosubstituted Pt(IV) tri- and tetra-hydroxido species could play important roles in the biological activity of this anticancer complex. Density Functional Theory (DFT) and Time-Dependent DFT (TDDFT) calculations show that these Pt(IV) species arising from FM-190 in aqueous media can be formed directly from a singlet excited state. The results highlight how speciation analysis (metallomics) can shed light on photoactivation pathways for FM-190 and formation of potential excited-state pharmacophores. The ability to detect and identify photoproducts at physiologically-relevant concentrations in cells and tissues will be important for preclinical development studies of this class of photoactivatable platinum drugs.

New heteroarene-fused anthraquinones: Synthesis and PyBOP-mediated amination

In this study three independent synthetic approaches for fusing of oxo-bearing aza-heterocycles to the anthraquinone core were developed. In particular, quinoline-2-one, pyrimidine-4-one, pyrimidine-2,4-dione,[1,2,3]triazine-4-one, quinoxaline-2-one, quinoxaline-2,3-dione, and imidazole-2-one were successfully annelated expanding the scope of heteroarene-fused anthraquinone derivatives. Cyclic amines were introduced as potential pharmacophore fragments by the PyBOP-mediated substitution of the oxo group. The amination requires relatively mild conditions yielding the products with reasonable-to-good effectiveness, however some limitations were found. This work contributes to the synthesis and chemical modification of heteroarene-fused anthraquinone derivatives for application in anticancer research as potential protein-kinase inhibitors.

Carbamate as a potential anti-Alzheimer's pharmacophore: A review.

Alzheimer's disease (AD) is a progressive age-related neurodegenerative brain disorder, which leads to loss of memory and other cognitive dysfunction. The underlying mechanisms of AD pathogenesis are very complex and still not fully explored. Cholinergic neuronal loss, accumulation of amyloid plaque, metal ions dyshomeostasis, tau hyperphosphorylation, oxidative stress, neuroinflammation, and mitochondrial dysfunction are major hallmarks of AD. The current treatment options for AD are acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and NMDA receptor antagonists (memantine). These FDA-approved drugs mainly provide symptomatic relief without addressing the pathological aspects of disease progression. So, there is an urgent need for novel drug development that not only addresses the basic mechanisms of the disease but also shows the neuroprotective property. Various research groups across the globe are working on the development of multifunctional agents for AD amelioration using different core scaffolds for their design, and carbamate is among them. Rivastigmine was the first carbamate drug investigated for AD management. The carbamate fragment, a core scaffold of rivastigmine, act as a potential inhibitor of acetylcholinesterase. In this review, we summarize the last 10 years of research conducted on the modification of carbamate with different substituents which primarily target ChE inhibition, reduce oxidative stress, and modulate Aβ aggregation.

Extraction, Purification and Characterisation of four new alkaloids from the water plant Pistia stratiotes: POM Analyses and Identification of Potential Pharmacophore Sites

Currently, during the period of intensive development of scientific production, it is important to obtain phytopreparations from sources of raw materials of plant origin. The biological diversity of plants is amazing. The study of the composition of aquatic plants rich in active substances of biotechnological significance is currently an urgent problem. Biologically active substances are involved in various regenerative reactions and metabolic processes in the organism, being part of enzymes. Alkaloids are important nitrogenous compounds found in the plant and are widely used in medicine. The aim of the present study was to identify alkaloid compounds from the composition of the aquatic plant Pistia stratiotes, grown in a model experiment in laboratory conditions by highly effective liquid chromatography and determine the molecular structure by nuclear magnetic resonance. In addition, based on the molecular structure of alkaloid compounds found in the aquatic plant Pistia stratiotes, a study of the properties of pharmaceutical activity was conducted on the pharmaceutical site POM (Petra/Osiris/Molinspiration). According to the results of the study, 4 types of identified alkaloids were identified by the IR, 1H, 13C-NMR method. They: 1-Aza-10-methoxy-4-methyl-2-oxo-1,2-dihydroanthracene-9-O-b-D-glucopyranoside, 4,6-dimethoxy-8-prenyloxyfuroquinoline, 4,7-dimethoxy-6 - (3’ - methyl-3’ - methoxy-2 ' - oxy) butyl-oxifuroquinoline , 4,7-dimethoxy-6 - (3’ - methyl-2’ - oxy-3 ' - chlorine)butyloxifuroquinoline. As a result of the analysis of the identified POM alkaloids (Petra/Osiris/Molinspiration), predictions of antitumor activity were made. The presence of a (NHd+--- Od-) moiety indicates a potential antitumor pharmacophore site. The challenge is to verify our hypothesis experimentally and to confront virtual POM data and real anticancer screening.

Algal Nanoparticles and Their Antibacterial Activity: Current Research Status and Future Prospectives

Green nanotechnology is a promising technology that has a wide range of applications in pharmaceuticals today because they offer a higher surface-area-to-volume ratio. Algal-based nanoparticles (NPs) are the subject of intense research interest today for their potential to treat and prevent infections caused by infectious microorganisms that are antibiotic resistant. Algae contain a variety of therapeutically potential bioactive ingredients, including chlorophyll, phycobilin, phenolics, flavonoids, glucosides, tannins, and saponins. As a result, NPs made from algae could be used as therapeutic antimicrobials. Due to their higher surface-area-to-volume ratios compared to their macroscopic components, metallic nanoparticles are more reactive and have toxic effects on their therapy. For pharmaceutical and biomedical applications, green synthesis restricts the use of physical and chemical methods of metallic nanoparticle synthesis, and it can be carried out in an environmentally friendly and relatively low-cost manner. The majority of macroalgae and some microalgae have latent antimicrobial activity and are used in the synthesis of metallic nanoparticles. A potential application in the field of nanomedicine and the establishment of a potential pharmacophore against microorganisms may result from the synthesis of algal-based NPs. Only a few studies have been done on the potential antimicrobial, antifungal, and antibacterial activity of algae-based NPs. As a result, the study will concentrate on the environmentally friendly synthesis of various NPs and their therapeutic potential, with a focus on their antibacterial activity. Thus, the aim of this study is to review all the literature available on the synthesis and characterization of the algal nanoparticles and their potential application as an antibacterial agent.

DISCOVERY OF DONEPEZIL-LIKE COMPOUNDS AS POTENTIAL ACETYLCHOLINESTERASE INHIBITORS DETERMINED BY PHARMACOPHORE MAPPING-BASED VIRTUAL SCREENING AND MOLECULAR DOCKING

Objective&#x0D; Alzheimer's disease (AD) is the most common cause&#x0D; of dementia in older people due to abnormalities in&#x0D; the cholinergic system. Acetylcholinesterase has&#x0D; an important role in the regulation of the cholinergic&#x0D; system. Therefore, targeting AChE is one of the most&#x0D; promising strategies for the treatment of AD. Although&#x0D; several approved drugs to treat AD, it is still needed&#x0D; to develop potential inhibitor candidates. Therefore,&#x0D; the aim of this study is to discover newly donepezillike&#x0D; natural compounds and their synthetic derivatives&#x0D; targeting acetylcholinesterase enzyme (AChE).&#x0D; Material and Method&#x0D; A pharmacophore model of a known drug, donepezil&#x0D; was generated. Using the pharmacophore mapping&#x0D; module of the Discovery Studio 2021 program,&#x0D; the chemical library containing natural products&#x0D; and synthetic derivatives was screened. The&#x0D; pharmacokinetics and drug-likeness properties of the&#x0D; screened compounds were predicted by ADMET and&#x0D; Lipinski and Veber’s rule. Some criteria were used as a&#x0D; filter. In addition, bioactive compounds of the database&#x0D; were screened. Then, molecular docking study was&#x0D; performed by using Glide/SP of Maestro (Schrödinger,&#x0D; Inc.) to determine the potential molecules.&#x0D; Results&#x0D; The binding energies were determined for hit&#x0D; compounds after molecular modeling studies.&#x0D; Furthermore, H-bonding, pi-pi stacking, pi-cation,&#x0D; and pi-alkyl interactions between the protein-ligand&#x0D; complex have been identified by various amino acid&#x0D; residues such as Tyr, Asp, His, Trp, Arg. The results&#x0D; show that the potential compounds are a promising&#x0D; candidate with binding energy compared to donepezil.&#x0D; The molecular modeling results indicate that new&#x0D; scaffolds may contribute to the discovery of new AChE&#x0D; inhibitors compared to a reference drug.&#x0D; Conclusion&#x0D; This study may lead to further studies and contribute to&#x0D; examination with in vitro analysis. The scaffolds can be&#x0D; used to design novel and effective inhibitors.