Medicinal Agents Research Articles

Eugenol Suppresses Platelet Activation and Mitigates Pulmonary Thromboembolism in Humans and Murine Models.

Platelets assume a pivotal role in the pathogenesis of cardiovascular diseases (CVDs), emphasizing their significance in disease progression. Consequently, addressing CVDs necessitates a targeted approach focused on mitigating platelet activation. Eugenol, predominantly derived from clove oil, is recognized for its antibacterial, anticancer, and anti-inflammatory properties, rendering it a valuable medicinal agent. This investigation delves into the intricate mechanisms through which eugenol influences human platelets. At a low concentration of 2 μM, eugenol demonstrates inhibition of collagen and arachidonic acid (AA)-induced platelet aggregation. Notably, thrombin and U46619 remain unaffected by eugenol. Its modulatory effects extend to ATP release, P-selectin expression, and intracellular calcium levels ([Ca2+]i). Eugenol significantly inhibits various signaling cascades, including phospholipase Cγ2 (PLCγ2)/protein kinase C (PKC), phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3β, mitogen-activated protein kinases, and cytosolic phospholipase A2 (cPLA2)/thromboxane A2 (TxA2) formation induced by collagen. Eugenol selectively inhibited cPLA2/TxA2 phosphorylation induced by AA, not affecting p38 MAPK. In ADP-treated mice, eugenol reduced occluded lung vessels by platelet thrombi without extending bleeding time. In conclusion, eugenol exerts a potent inhibitory effect on platelet activation, achieved through the inhibition of the PLCγ2-PKC and cPLA2-TxA2 cascade, consequently suppressing platelet aggregation. These findings underscore the potential therapeutic applications of eugenol in CVDs.

Monoterpenes as Medicinal Agents: Exploring the Pharmaceutical Potential of p-Cymene, p-Cymenene, and γ-Terpinene

This review highlights the therapeutic propeties of monoterpenes, particularly γ-terpinene, p-cymene, and p-cymenene, found in essential oils derived from various plants. These compounds are known for their analgesic, anticancer, anti-inflammatory, and antimicrobial properties. γ-Terpinene is recognized for its potent antioxidant propeties and is a constituent of oils from plants such as cumin and thyme. p-cymene, found in over 100 plant species, is noted for its antiviral and antibacterial properties and is considered safe by IFRA standards. p-Cymenene, with its distinct aroma, is detected in parsley and turmeric oils and is known for its antibacterial and antioxidant activities. The antimicrobial properties of γ-terpinene and p-cymene are highlighted, demonstrating their effectiveness in treating various skin conditions and reducing airborne microbes. Their selective antimicrobial activity preserves the integrity of the microbiome, offering a balanced approach to infection control. The anti-inflammatory properties of γ-terpinene are emphasized, with studies indicating its role in modulating cytokine production, underscoring its potential in the treatment of inflammation. Additionally, its antinociceptive effects suggest that it is a safe analgesic. In cancer treatment, the antiproliferative effects of γ-terpinene and p-cymene are being explored, highlighting their potential for targeted cancer therapy. This review aims to consolidate knowledge about these monoterpenes and promote a deeper understanding of their medical applications and safety. The knowledge gained is expected to stimulate further research, potentially leading to innovative applications in pharmaceutical and medical fields and harnessing the potential of -terpinene, p-cymene, and p-cymenene.

Opportunities and Difficulties in the Repurposing of HDAC Inhibitors as Antiparasitic Agents

Ongoing therapy for human parasite infections has a few known drugs but with serious side effects and the problem of drug resistance, impelling us to discover novel drug candidates with newer mechanisms of action. Universally, this has boosted the research in the design and development of novel medicinal agents as antiparasitic drugs with a novel mode of action. Histone deacetylase inhibitors (HDACis) are used in a vast variety of diseases due to their anti-inflammatory properties. Drug repurposing strategies have already approved HDACis as cancer therapeutics and are now under investigation for many parasitic infections. Along with the expression of the gene, histone deacetylase (HDAC) enzymes also act as a slice of great multi-subunit complexes, targeting many non-histones, changing systemic and cellular levels signaling, and producing different cell-based specified effects. Zinc (Zn2+)- and nicotinamide adenine dinucleotide (NAD+)-dependent HDACs of parasites play pivotal roles in the alteration of gene expression of parasites. Some of them are already known to be responsible for the survival of several parasites under odd circumstances; thus, targeting them for therapeutic interventions will be novel for potential antiparasitic targets. This point of view outlines the knowledge of both class-I and class-II HDACis and sirtuin inhibitors that emerged to be the key players in the treatment of human parasitic disorders like Leishmaniasis, Schistosomiasis, Malaria, Trypanosomiasis, and Toxoplasmosis. This review also focuses on repurposing opportunities and challenges in HDAC inhibitors that are preceded by their clinical development as potent new antiparasitic drugs.

Indole-Containing Metal Complexes and Their Medicinal Applications.

Indole is an important element of many natural and synthetic molecules with significant biological activity. Nonetheless, the co-presence of transitional metals in organic scaffold may represent an important factor in the development of effective medicinal agents. This review covers some of the latest and most relevant achievements in the biological and pharmacological activity of important indole-containing metal complexes in the area of drug discovery.

Effect of Dill (Anethum graveolens) Oil on Pruritus and Quality of Life of Hemodialysis Patients: A Randomized Double-Blind Three-Arm Controlled Trial.

Anethum graveolens (AG), commonly known as dill, is a plant from the Apiaceae family that has been traditionally used as a skin softener and purifying agent in Persian medicine. In a previous study conducted on male rats, dill was found to have anti-inflammatory effects. The current study aimed to examine the efficacy of topical application of Anethum graveolens oil on pruritus severity, skin dryness, sleep quality, and quality of life in patients undergoing hemodialysis. In the current clinical trial, the participants were randomly assigned to one of these groups: topical AG preparation, sesame oil, or a control group receiving no treatment. The study was double-blind and placebo-controlled. The topical treatment was applied twice a day for one month to areas of the skin affected by pruritus. The outcome measures included the severity of skin dryness, the Pittsburgh Sleep Quality Index, Duo's Uremic Pruritus Severity Scale, and the Itchy QoL questionnaire. This study involved 106 hemodialysis patients, and after intervention for one month, the medication group had a significantly lower mean score of sleep quality (3.24 ± 2.41) than the placebo (4.54 ± 3.11) and control (5.05 ± 3.21) groups (P=0.032). The mean change in pruritus severity was significantly greater in the medication group (-17.28 ± 8.938) than the placebo (-5.91 ± 5.398) and control (-3.43 ± 3.228) groups (P < 0.001). Moreover, a significant difference was observed in the mean changes in quality of life between the medication, placebo, and control groups, with values of -14.88 ± 7.89, -5.34 ± 4.50, and -1.92 ± 2.86, respectively (P < 0.001). Furthermore, both the medication and placebo groups showed improvement in skin dryness compared to the control group having the values of -1.65 ± 0.91, -1.11 ± 0.79, and -0.38 ± 0.54, respectively (P < 0.001). Topical Anethum graveolens preparation significantly improved the sleep quality and quality of life and reduced skin pruritus and dryness in hemodialysis patients. It could be considered as a simple therapeutic modality to control pruritus in hemodialysis patients. This trial is registered with IRCT2017022032671N1.

Recent Advances in Pyrimidine-Based Drugs.

Pyrimidines have become an increasingly important core structure in many drug molecules over the past 60 years. This article surveys recent areas in which pyrimidines have had a major impact in drug discovery therapeutics, including anti-infectives, anticancer, immunology, immuno-oncology, neurological disorders, chronic pain, and diabetes mellitus. The article presents the synthesis of the medicinal agents and highlights the role of the biological target with respect to the disease model. Additionally, the biological potency, ADME properties and pharmacokinetics/pharmacodynamics (if available) are discussed. This survey attempts to demonstrate the versatility of pyrimidine-based drugs, not only for their potency and affinity but also for the improved medicinal chemistry properties of pyrimidine as a bioisostere for phenyl and other aromatic π systems. It is hoped that this article will provide insight to researchers considering the pyrimidine scaffold as a chemotype in future drug candidates in order to counteract medical conditions previously deemed untreatable.

Synthesis of biogenic silver and gold nanoparticles from Anemopsis californica extract with antibacterial and cytotoxic activities

Silver (Ag) and gold (Au) nanoparticles, have gained attention for their unique properties and diverse applications, including medicine and antimicrobial agents. To meet the demand for eco-friendly synthesis methods, we explored plant-mediated nanoparticle synthesis using Anemopsis californica extracts. The Anemopsis californica leaves were used to extract bioactive compounds with water, methanol, and isopropanol. These extracts served as reducing and stabilizing agents for Ag and Au nanoparticle synthesis. The process involved mixing the extract, a metallic precursor solution, and deionized water in specific volume ratios, resulting in nanoparticles denoted as W-(Ag or Au), M-(Ag or Au), and I-(Ag or Au) for water, methanol, and isopropanol, respectively. The synthesized nanoparticles ranged from 5 to 30 nm in size and displayed various shapes. UV-Vis spectroscopy confirmed their presence with surface plasmon resonance bands. Antibacterial tests on Staphylococcus aureus and Escherichia coli showed significant antibacterial effects of Ag nanoparticles, especially those synthesized in methanol. In contrast, Au nanoparticles had limited antibacterial impact, regardless of the solvent. Cytotoxicity evaluations with macrophage cells indicated that Ag nanoparticles were more cytotoxic than Au nanoparticles, with the synthesis solvent influencing cytotoxicity. The observed antibacterial effects of Ag nanoparticles align with their reputation as potent antimicrobial agents, particularly against Gram-positive strains. The limited antibacterial impact of Au nanoparticles suggests differences in their antibacterial mechanisms. Varying cytotoxicity between Ag and Au nanoparticles underscores the significance of the chosen synthesis method in shaping nanoparticle properties.

Nickel-Catalyzed Reductive Arylation of Redox Active Esters for the Synthesis of α-Aryl Nitriles: Investigation of a Chlorosilane Additive.

A nickel-catalyzed reductive cross-coupling of redox active N-hydroxyphthalimide (NHP) esters and iodoarenes for the synthesis of α-aryl nitriles is described. The NHP ester substrate is derived from cyanoacetic acid, which allows for a modular synthesis of substituted α-aryl nitriles, an important scaffold in the pharmaceutical sciences. The reaction exhibits a broad scope, and many functional groups are compatible under the reaction conditions, including complex highly functionalized medicinal agents. Mechanistic studies reveal that reduction and decarboxylation of the NHP ester to the reactive radical intermediate are accomplished by a combination of a chlorosilane additive and Zn dust. We demonstrate that stoichiometric chlorosilane is essential for product formation and that chlorosilane plays a role beyond activation of the metal reductant.

Multi-biological activity assessment and phytochemical characterization of an aqueous extract of the Cymbopogon citratus grown in Palestine

BackgroundPlants have historically been a rich source of medicinal compounds, with many modern pharmaceuticals derived from botanical origins. In contemporary healthcare, there is a resurgence in utilizing botanical substances as recognized medicinal agents. This study delved into understanding the phytochemical makeup and the multifaceted biological activities of an aqueous extract from Cymbopogon citratus (C. citratus). The investigated activities were its effect on AMPA receptors, antioxidant capacity, anti-lipase, anti-α-amylase actions, cytotoxicity, and antimicrobial properties.MethodsThe extract of C. citratus received a comprehensive investigation, which included the study of its phytochemical composition, assessment of its antioxidant and anti-lipase properties, evaluation of its capacity to inhibit α-amylase, analysis of its impact on cell viability, and assessment of its antimicrobial activity. The approaches are used to clarify the complex physiological and biochemical characteristics.ResultsThe results were compelling; receptor kinetics had a marked impact, notably on the GluA2 subunit. Regarding its medicinal potential, the extract demonstrated potent antioxidant and anti-diabetic activities with IC50 values of 15.13 and 101.14 µg/mL, respectively. Additionally, it displayed significant inhibitory effects on the lipase enzyme and showed cytotoxicity against the Hep3B cancer cell line, with IC50 values of 144.35 and 148.37 µg/mL. In contrast, its effects on the normal LX-2 cell line were minimal, indicating selectivity.ConclusionThe aqueous extract of C. citratus shows promising therapeutic properties. The findings advocate for further research into its compounds for potential isolation, purification, and in-depth pharmacological studies, especially in areas like nervous system disorders, diabetes, obesity, and combating oxidative stress.

Immunoliposomes As a Promising Antiviral Agent against SARS-CoV-2

According to the World Health Organization, as of January 3, 2020 to September 13, 2023, there were approximately 23 million confirmed cases of COVID-19 reported in the Russian Federation, about 400 thousand of which were fatal. Considering the high rate of mutation of the RNA-containing virus genome, which inevitably leads to the emergence of new infectious strains (Eris and Pyrola), the search for medicinal antiviral agents remains an urgent task. Moreover, taking into account the actively mutating receptor-binding domain, this task requires fundamentally new solutions. This study proposes a candidate immunoliposomal drug that targets the S protein of SARS-CoV-2 by the monoclonal neutralizing antibody P4A1 and ensures the penetration of a highly active ribonuclease into the virus-infected cell, which degrades, among cellular RNA, viral RNA too. We demonstrate a more than 40-fold increase in the neutralizing activity of the developed drug compared to the free monoclonal neutralizing antibody.

Determination of antioxidant and anti-inflammatory properties of Salvia aethiopis/sclarea and synthesized silver nanoparticles

Aim: In the study, the phenolic compounds of Salvia aethiopis/sclarea will be determined and the antioxidant and anti-inflammatory activities of the extracts of these plants and the synthesized silver nanoparticles (AgNP) will be examined in vitro. Materials and Methods: Extracts obtained from Salvia spp. (SE) collected from the Kyrenia region of Cyprus were used in the study. Methanol extracts were prepared and total phenolic, flavonoid and alkaloid contents were determined. The amount of phenolic compounds was then quantified and identified using HPLC. The antioxidant properties of Salvia aethiopis/sclarea were analyzed using various markers, including lipid peroxidation inhibition activity, 1,1-Diphenyl-2-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) scavenging capacity. Additionally, their anti-inflammatory effects were investigated by proteinase inhibitor activity, heat-induced hemolysis and albumin denaturation analyses. Results: S. aethiopis and S. sclarea were contained high levels of the phenolic compounds isoquercetin and caffeic acid or naringenin and caffeic acid, respectively. After green synthesis of silver nanoparticles, the antioxidant and anti-inflammatory properties of plant extracts increased significantly (p&lt;0.05). Conclusion: Our study found that silver nanoparticles synthesized using S. aethiopis/sclarea extract increased the antioxidant and anti-inflammatory effects of plant extracts and suggested that AgNP/SE could be used as a potential therapeutic agent in medicine.

Digital Agents in Medicine: New Opportunities and Challenges

Digital Agents in Medicine: New Opportunities and Challenges

NSAIDs between past and present; a long journey towards an ideal COX-2 inhibitor lead.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most abundantly used classes among therapeutic agents in medicine. NSAIDs inhibit the enzyme cyclooxygenase (COX), which is responsible for the conversion of arachidonic acid to prostaglandins. Meanwhile, non-selective NSAIDs are considered as a double-edged weapon since inhibition of COX-1 can lead to gastrointestinal side effects and kidney damage, whereas selective COX-2 inhibition provides anti-inflammatory effects without gastrointestinal toxicity. The detection of COX-2 role in inflammation process launched a new era in its management. Several trials have been established to proceed towards selectivity of well-defined anti-inflammatory members. COX-2 selective inhibitors are evidently safer on the gastrointestinal tract than non-selective NSAIDs. Nevertheless, their unexpected cardiovascular risks cannot be ignored. This review article highlights the latest trials aimed at developing new compounds with promising selective COX-2 activity.

Natalizumab intake during pregnancy in women with multiple sclerosis: a meta-analysis of current evidence

Background: Disease-modified therapy has changed the previous practice of discontinuing multiple sclerosis (MS) treatment for fear of side effects that might impact pregnancy. Many studies have described the use of natalizumab as a medicinal agent during pregnancy, with mixed results regarding its safety and efficacy during pregnancy. For instance, this study aimed to investigate the pregnancy outcomes in pregnant women with MS who took natalizumab during the pregnancy period. Methods: A systematic literature search was conducted during July 2023, adhering to the PRISMA guidelines. Five databases were included: PubMed, Google Scholar, Web of Science, Virtual Health Library, and Scopus. The following keywords were employed in the search &amp;quot;multiple sclerosis,&amp;quot; &amp;quot;pregnancy,&amp;quot; &amp;quot;pregnancies, &amp;quot;pregnant,&amp;quot; and &amp;quot;natalizumab.&amp;quot; Results: Only eight papers out of 1,000 total records were included. No significant difference between natalizumab and the control group in terms of abortion, C-section, preterm birth, congenital abnormalities, or birth height was found (p &amp;gt; 0.05). However, the natalizumab-treated group had a significantly lower birth weight than the control group [Mean difference = -97.89; 95% confidence interval (CI) = -171.32, -24.45], with 82.7% relapse rate (95% CI = 72.1-89.8), being highest in the second trimester (24.9%; 95% CI = 7.4, 58.0). Conclusion: While Natalizumab treatment appears to be relatively safe in terms of abortion rates, C-section rates, preterm delivery rates, and congenital anomalies, the increased relapse rate during pregnancy and lower birth weight observed necessitate careful monitoring and individualized care for pregnant MS patients taking natalizumab.

Time-resolved keto-enol tautomerization of the medicinal pigment curcumin.

Curcumin is a medicinal agent that exhibits anti-cancer and anti-Alzheimer's disease properties. It has a keto-enol moiety that gives rise to many of its chemical properties including metal complexation and acid-base equilibria. A previous study has shown that keto-enol tautomerization at this moiety is implicated in the anti-Alzheimer's disease effect of curcumin, highlighting the importance of this process. In this study, tautomerization of curcumin in methanol, acetone and acetonitrile was investigated using time-resolved 1H nuclear magnetic resonance spectroscopy. Curcumin undergoes hydrogen-deuterium exchange with the solvents and the proton resonance peak corresponding to the hydrogen at the α-carbon position (Cα) decays as a function of time, signifying deuteration at this position. Because tautomerization is the rate limiting step in the deuteration of curcumin at the Cα position, the rate of tautomerization is inferred from the rate of deuteration. The rate constant of tautomerization of curcumin shows a temperature dependence and analysis using the Arrhenius equation revealed activation energies (Ea) of tautomerization of (80.1 ± 5.9), (64.1 ± 1.0) and (68.3 ± 5.5) kJ mol-1 in methanol, D2O/acetone and D2O/acetonitrile, respectively. Insight into the role of water in tautomerization of curcumin was further offered by density functional theory studies. The transition state of tautomerization was optimized in the presence of water molecules. The results show a hydrogen-bonded solvent bridge between the diketo moiety and Cα of curcumin. The Ea of tautomerization of curcumin shows a strong dependence on the number of water molecules in the solvent bridge, indicating the critical role played by the solvent bridge in catalyzing tautomerization of curcumin.

Unlocking the regenerative key: Targeting stem cell factors for bone renewal.

Stem cell factors (SCFs) are pivotal factors existing in both soluble and membrane-bound forms, expressed by endothelial cells (ECs) and fibroblasts throughout the body. These factors enhance cell growth, viability, and migration in multipotent cell lineages. The preferential expression of SCF by arteriolar ECs indicates that arterioles create a unique microenvironment tailored to hematopoietic stem cells (HSCs). Insufficiency of SCF within bone marrow (BM)-derived adipose tissue results in decreased their overall cellularity, affecting HSCs and their immediate progenitors critical for generating diverse blood cells and maintaining the hematopoietic microenvironment. SCF deficiency disrupts BM function, impacting the production and differentiation of HSCs. Additionally, deleting SCF from adipocytes reduces lipogenesis, highlighting the crucial role of SCF/c-kit signaling in controlling lipid accumulation. This review elucidates the sources, roles, mechanisms, and molecular strategies of SCF in bone renewal, offering a comprehensive overview of recent advancements, challenges, and future directions for leveraging SCF as a key agent in regenerative medicine.

Thymoquinone: An Effective Natural Compound for Kidney Protection.

Kidney disease is a common health problem worldwide. Acute or chronic injuries may interfere with kidney functions, eventually resulting in irreversible kidney damage. A number of recent studies have shown that the plant-derived natural products have an extensive potential for renal protection. Thymoquinone (TQ) is an essential compound derived from Nigella Sativa (NS), which is widely applied in the Middle East as a folk medicine. Previous experiments have demonstrated that TQ has a variety of potential pharmacological effects, including anti-oxidant, antibacterial, antitumor, immunomodulatory, and neuroprotective activities. In particular, the prominent renal protective efficacy of TQ has been demonstrated in both in vivo and in vitro experiments. TQ can prevent acute kidney injuries from various xenobiotics through anti-oxidation, anti-inflammatory, and anti-apoptosis effects. In addition, TQ exhibited significant pharmacological effects on renal cell carcinoma, renal fibrosis, and urinary calculi. The essential mechanisms involve scavenging ROS and increasing anti-oxidant activity, decreasing inflammatory mediators, inducing apoptosis, and inhibiting migration and invasion. The purpose of this review is to conclude the pharmacological effects and the potential mechanisms of TQ in renal protection, shedding new light on the exploration of medicinal phyto-protective agents targeting kidneys.

Antibacterial activity against Staphylococcus aureus and Salmonella enterica and Density functional studies on Silver doped Bismuth Selenide nanostructures

The current study uses a hydrothermal technique to demonstrate the antibacterial activity of silver- doped bismuth selenium nanoparticles. Because they are more biocompatible, nanoparticles made of metals, polymers, or lipids are better suited as antibiotics. They behave like molecules, breaking through bacterial cell membranes to obstruct the molecular process. According to the studies, the activity against bacteria is caused by the host immune system being triggered, RNA and protein synthesis being inhibited, biofilm development being inhibited, cell membrane disruption occurring, or reactive oxygen species (ROS) being produced. Low toxicity and a well-established medicinal agent characterize bismuth. It had the property of good X-ray contrast agent due it is huge atomic mass (Z=83). The human body need selenium as a necessary component. In the present work, the prepared Ag doped bismuth selenide nanostructures are characterized using XRD, HRSEM with EDAX. The antibacterial property of Ag doped bismuth selenide nanostructures against gram-positive bacteria S. aureus and gram negative Salmonella enterica analysed by disk diffusion method. The optimized structure, structural parameters, Homo-Lomo, molecular electrostatic potential, dipole moments, polarizability and hyperpolarazibilary are analyzed using DFT method.

Exploiting thiol-functionalized benzosiloxaboroles for achieving diverse substitution patterns – synthesis, characterization and biological evaluation of promising antibacterial agents

A series of new benzosiloxaboroles with diverse substitution patterns were synthesized from simple SH-substituted precursors followed by comprehensive characterization and evaluation as promising antibacterial agents.

Coordination Complexes of Copper, Silver and Gold with SNO Group Containing Thiosemicarbazones Schiff Base Ligands and their Biological Applications

The thiosemicarbazone Schiff base ligand is very important segment for chemistry, more specifically coordination chemistry. These compounds and their complexes widely used as medicinal agents for different lethal diseases such as cancer and other contagious disease caused by bacteria. The coordinated metal (coinage) complexes exhibited higher activities than free ligand for all the biological investigation of anticancer and antibacterial activities. The TSCs ligands having polydentate S-N-O coordinating sites. The mode of coordination of these ligands is flexible, it can act as tridentate or bidentate ligand. These ligand form mostly square planar complexes with copper, silver and gold metal ions. This research content could guide to identify the synthesized biomaterial. In this review, copper, silver, gold complexes are comprehensively summarized, and their activities and mechanism are documented. This review will provide very cut-edge guide of TSCs and their complexes to use in different field.