Anti-inflammatory & anti-allergy agents in medicinal chemistry最新文献

The potential of underutilized plant species to improve food security, health, economic output, and the environment has not been fully realized. Sri Lanka an island on the Indian Ocean is home to numerous plant species with significant medicinal potential, including many underutilized plants that could help meet the growing demand for food, energy, medicines, and industrial resources. Globally, there are over a thousand known and unknown phytochemicals derived from plants. Although these compounds are primarily produced by plants for self-defence, in vitro and in vivo studies have demonstrated their anti-inflammatory properties. Recent research indicates that several phytochemicals can also protect humans from disease by regulating key inflammatory pathways, such as NF-κB, MAPK, JAK/STAT and Nrf-2, which are involved in autoimmune diseases. Thus, these bioactive compounds are vital for managing managing immune related conditions. This review will explore underutilized fruit crops from Sri Lanka that could be used against inflammation, including autoimmune diseases.

Background: The presence of insufficient insulin signaling in type 2 diabetes arises due to either insulin resistance or impaired insulin secretion, ultimately leading to elevated blood glucose levels, a condition known as hyperglycemia. Diabetes poses a pervasive worldwide challenge, with its prevalence steadily surging in both developed and developing nations. A promising avenue for improving the management of diabetes type 2 involves the exploration of glucokinase activators as an innovative therapeutic target. Notably, a recent breakthrough in this area has been the market approval granted by the Japanese FDA for the use of the innovative GKA, Dorzagliatin, in the treatment of diabetes type 2.

Objectives: To augment the management of diabetes type 2 and mitigate the undesirable side effects linked to prolonged use of conventional medications, this research endeavor sought to create innovative glucokinase activators.

Methods: The ZINC database yielded a collection of 56 compounds, each showcasing a 40% structural similarity to 1-(phenylsulfonyl)-1H-indole-2-carboxylic acid. These compounds, all featuring the distinctive indole core, were meticulously selected for further investigation. Structural illustrations were crafted using ChemBioDraw Ultra, and 1.5.6 AutoDock Vina was for molecular docking. The Swiss ADME algorithm facilitated online log P predictions, while the software PKCSM was utilized to forecast the toxicity profiles of the leading compounds. DFT analysis was done to ensure the stability of compounds by using Gaussian 16 quantum chemistry software and Mulliken charge distributions used to optimize molecular geometries.

Results: Among all the compounds, RS33 and RS37 exhibited the highest affinities for GK receptors, with the docking scores of -8.93 and -8.44 kcal/mol, respectively. These compounds follow Lipinski's Rule, indicating promising absorption and excretion profiles through the gastrointestinal tract. Compared to standard drugs Dorzagliatin (GKA) and MRK (co-crystallized ligand), both RS33 and RS37 demonstrate no AMES toxicity, skin sensitization, and hepatotoxicity. RS43 is the most stable compound as it has high ΔE, η, and χ in DFT analysis.

Conclusion: The novel-designed lead molecules demonstrate an enhanced pharmacokinetic profile, superior binding affinity, and minimal toxicity, based on computational study. These attributes make them promising candidates for further optimization as glucokinase activators.

Background: Seeds of plant Scaphium affine are traditionally used by the healers of "India" for the treatment of piles.

Objectives: The primary objective of the study was to assess the anti-hemorrhoidal potential of the ethanolic seed extract of Scaphium affine.

Methods: After the soxhlet extraction method, the seed extract from Scaphium affine was first submitted to phytochemical standardization and then GC-MS analysis. Rats were given Croton oil and Jatropha oil to develop hemorrhoids, and Scaphium affine seed extract (ESA) was administered orally for 5 days and 3 days, respectively, at doses of 1000 and 500 mg/kg. The Rectoanal coefficient (RAC) was calculated as an inflammatory marker. The hemorrhoidal tissues were also subjected to cytokine profiling, biochemical estimation and histopathology.

Results: ESA demonstrated the presence of flavonoids, saponins, phytosterols, phenols, and tannins. GCMS analysis elucidated the presence of hexadecanoic acid 2 hydroxy -1,3 propane diyl ester,9 Octadecanoic acid ethyl ester, Cyclohexane 1,4 di methyl cis, Farnesol isomer,1, E-11, Z-13 octa decatriene, Stigmasterol, N-(5 ethyl -1,3,4-thiadiazol-yl) benzamide, N, N Dinitro 1,3,5,7 tetraza bicyclo 93,3,1) as major phytoconstituents. The results depicted more potent anti-hemorrhoidal activity of ESA at 1000 mg/kg, p.o., which was evident through a decrease in RAC. A significant decline in the levels of IL-1β, IL-6, and TNF-α expression was observed, along with the restoration of altered antioxidants and enzymes. Histopathological analysis confirmed the tissue recovery as it revealed minimal inflammation and decreased dilated blood vessels in treated animals.

Conclusion: Based on the results it can be concluded that seeds of Scaphium affine showed significant anti-hemorrhoid agents which may be attributed to their anti-inflammatory and anti-oxidant potential due to the presence of certain phytoconstituents in it. The study also supports the traditional use of seeds of Scaphium affine for the first time in the treatment of hemorrhoids.

Background: Benzo[d]thiazoles represent a significant class of heterocyclic compounds renowned for their diverse pharmacological activities, including analgesic and antiinflammatory properties. This molecular scaffold holds substantial interest among medicinal chemists owing to its structural versatility and therapeutic potential. Incorporating the benzo[d]thiazole moiety into drug molecules has been extensively investigated as a strategy to craft novel therapeutics with heightened efficacy and minimized adverse effects.

Aims: The aim of the present research work was to design, synthesize and characterize the new benzo[d]thiazol-2-amine derivatives as potent analgesic and anti-inflammatory agents.

Materials and methods: The synthesis of the presented benzo[d]thiazol-2-amine derivatives was performed by condensing-(4-chlorobenzylidene) benzo[d]thiazol-2-amine with a number of substituted phenols in the presence of potassium iodide and anhydrous potassium carbonate in dry acetone. IR spectroscopy, 1HNMR spectroscopy, 13CNMR spectroscopy and Mass spectroscopy methods were used to characterize the structural properties of all 13 newly synthesized derivatives. The molecular properties of these newly synthesized derivatives were estimated to study the attributes of drug-like candidates. Benzo[d]thiazol-2-amine derivatives were molecularly docked with selective enzymes COX-1 and COX-2. Analgesic and anti-inflammatory activities of synthesized compounds were evaluated by using albino rats.

Results: Findings of the research suggested that compounds G3, G4, G6, G8 and G11 possess higher binding affinity than diclofenac sodium, when docking was performed with enzyme COX-1. Compounds G1, G3, G6, G8 and G10 showed lower binding affinity than Indomethacin when docking was performed with enzyme COX-2. In vitro evaluation of the COX-1 and COX-2 enzyme inhibitory activities was performed for synthesized compounds.

Discussion: Compounds G10 and G11 exhibited significant COX-1 and COX-2 enzyme inhibitory action with an IC₅₀ value of 5.0 and 10 μM, respectively. Using the hot plate method and the carrageenan-induced rat paw edema model, the synthesized compounds were screened for their biological activities, including analgesic and anti-inflammatory activities. Highest analgesic action was exhibited by derivative G11 and the compound G10 showed the highest anti-inflammatory response. Inhibition of COX may be considered as a mechanism of action of these compounds.

Conclusion: It was concluded that synthesized derivatives G10 and G11 exhibited significant analgesic and anti-inflammatory effect; therefore, the said compounds may be subjected to further clinical investigation for establishing these as future compounds for the treatment of pain and inflammation.

A typographical error in the Reference No. 175 appeared erroneously in the References List of the article titled "Anti- SARSCoV- 2 IgG and IgM Levels in Iraqi General Population", 2023; 22(2) [1]. Original: Barassi, A.; Pezzilli, R.; Mondoni, M.; Rinaldo, R.F.; Dav, I.M.; Cozzolino, M. Vitamin D in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients with non-invasive ventilation support. Panminerva Med., 2021, ••• Corrected: Barassi, A.; Pezzilli, R.; Mondoni, M.; Rinaldo, R.F.; Davì, M.; Cozzolino, M. Vitamin D in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients with non-invasive ventilation support. Panminerva Med., 2023, 65(1), 23-29. We apologize to the readers for the inconvenience caused due to this error. The original article can be found online at: https://www.eurekaselect.com/article/135111.

Aims: Leishmaniasis is a deadly tropical disease that is neglected in many countries. World Health Organization, along with a few other countries, has been working together to protect against these parasites. Many novel drugs from the past few years have been discovered and subjected against leishmaniasis, which have been effective but they are quite expensive for lower-class people. Some drugs showed no effect on the patients, and the longer use of these medicines has made resistance against these deadly parasites. Researchers have been working for better medication by using natural products from medicinal plants (oils, secondary metabolites, plant extracts) and other alternatives to find active compounds as an alternative to the current synthetic drugs.

Materials and methods: To find more potential natural products to treat Leishmania spp, a study has been conducted and reported many plant metabolites and other natural alternatives from plants and their extracts. Selected research papers with few term words such as natural products, plant metabolites, Leishmaniasis, in vivo, in vitro, and treatment against leishmaniasis; in the Google Scholar, PubMed, and Science Direct databases with selected research papers published between 2015 and 2021 have been chosen for further analysis has been included in this report which has examined either in vivo or in vitro analysis.

Results: This paper reported more than 20 novel natural compounds in 20 research papers that have been identified which report a leishmanicidal activity and shows an action against promastigote, axenic, and intracellular amastigote forms.

Conclusion: Medicinal plants, along with a few plant parts and extracts, have been reported as a possible novel anti-leishmanial medication. These medicinal plants are considered nontoxic to Host cells. Leishmaniasis treatments will draw on the isolated compounds as a source further and these compounds compete with those already offered in clinics.

Introduction: Ziziphus mauritiana, sometimes called Indian jujube or Ber, belongs to the Rhamnaceae group of plants. The aqueous and ethanolic Ziziphus mauritiana formulations were shown to have analgesic, antipyretic, potent analgesic, anti-inflammatory, and anti-emetic properties.

Aims & objectives: The aim of this study is to investigate the sedative and anticonvulsant activities of Ziziphus mauritiana extract by governing 200 and 400 mg/kg body weight orally.

Materials and methods: The leaves are extracted with ethanol and lukewarm water with a soxhlet apparatus for 72 hours. After that acute extract toxicity study was performed and then locomotor activity, pentobarbital induced sleeping time and anticonvulsant activity were performed with the extract.

Results: Oral administration of extract at dosages of 200 & 400 mg/kg was employed after an immediate toxicity test. At a dosage of 400 mg/kg, the number of locomotions was reduced significantly lengthened the period of time spent sleeping and there was showed a dosage-dependent reduction in all phases of an epileptic episode.

Conclusion: In this study, the extract reduced locomotor activity, however, it had a superior profile for an antiepileptic action than phenytoin since it decreased locomotor activity to a lesser level. The considerable increase in pentobarbitone sleep hours with the extracts at a higher dose supported the sedative action of Z. mauritiana.

Inflammation is a complex biological response that plays a pivotal role in various pathological conditions, including inflammatory diseases. The search for effective therapeutic agents has led researchers to explore natural products due to their diverse chemical composition and potential therapeutic benefits. This review comprehensively examines the current state of research on natural products as potential therapeutic agents for inflammatory diseases. The article discusses the antiinflammatory properties of various natural compounds, their mechanisms of action, and their potential applications in managing inflammatory disorders. Additionally, formulation and delivery systems, challenges and future prospects in this field are also highlighted.

Over the years, researchers have endeavored to identify dependable and reproducible in vitro models for examining macrophage behavior under controlled conditions. The THP-1 cell line has become a significant and widely employed tool in macrophage research within these models. Originating from the peripheral blood of individuals with acute monocytic leukemia, this human monocytic cell line can undergo transformation into macrophage-like cells, closely mirroring primary human macrophages when exposed to stimulants. Macrophages play a vital role in the innate immune system, actively regulating inflammation, responding to infections, and maintaining tissue homeostasis. A comprehensive understanding of macrophage biology and function is crucial for gaining insights into immunological responses, tissue healing, and the pathogenesis of diseases such as viral infections, autoimmune disorders, and neoplastic conditions. This review aims to thoroughly evaluate and emphasize the extensive history of THP-1 cells as a model for macrophage research. Additionally, it will delve into the significance of THP-1 cells in advancing our comprehension of macrophage biology and their invaluable contributions to diverse scientific domains.