Recent Progress in the Synthesis of Isoxazoles

: Isoxazole derivatives are aromatic five-membered ring heterocyclic compounds with one oxygen atom and one nitrogen atom at adjacent positions. These compounds have a broad spectrum of applications in medicinal chemistry, such as antimicrobial, anticancer, antitumor, antitubercular, analgesic, anti-inflammatory, antidepressant, and anticonvulsant activities and some of them are well-known drugs for the treatment of various diseases in the market. The use of this class of compounds in agriculture as herbicides, insecticides have been widely reported. In organic materials, these compounds have been applied as semiconductors, single-walled nanotubes, liquid crystals, chiral ligands, scaffolds for peptidomimetics, dyes, and high-temperature lubricants. Isoxazole derivatives also play an important role in organic synthesis because they can be converted into several important synthetic units such as β-hydroxy ketones, γ-amino alcohols, α,β-unsaturated oximes, β-hydroxy nitriles, α-hydroxy-β-diketones, and β-dicarbonyl compounds. Due to such a wide range of applicability, the synthesis of isoxazole derivatives has attracted intensive research from chemists. This review will focus on considerable studies on the synthesis of isoxazoles which date back from 2012.

Assessment of Anticonvulsant Activities of Petroleum Ether Extract of Anacyclus pyrethrum Roots on Experimental Rats

Background: Epilepsy is one of the most common neurological conditions and a significant cause of morbidity and mortality. Objectives: The present study aimed to evaluate the anticonvulsant activity of the petroleum ether extract of the root of Anacyclus pyrethrum on Pentylenetetrazole (PTZ)-induced seizure model in Wistar rats. Methods: The composition of the petroleum ether extract of A. pyrethrum was first analyzed using Gas Chromatography-Mass Spectrometry (GC-MS). Subsequently, the anticonvulsant activities of these extracts (70 and 140 mg/kg, intraperitoneal injection) were evaluated on PTZ-induced seizures in rats. The protection rate against induced seizures, latency, and duration of seizures, as well as neurological symptoms, were assessed and compared to those protected by phenobarbital. Results: GC/MS analysis of the petroleum ether extract showed that the main components were octadecadienoic acid, hexadecanoic acid, diheptylcyclopropene, naphthalene, and methyl stearate. The extract (70 and 140 mg/kg) was found to provide significant protection against PTZ-induced seizures. Moreover, compared to the negative control, the extracts increased the latency of induced-convulsion and reduced the duration of epilepsy. Interestingly, the extracts showed a reduction in neurological symptoms and the severity of seizures compared to the negative control. All of these outcomes manifested in a dose-dependent manner. Conclusion: The petroleum ether extract of A. pyrethrum may produce anticonvulsant effects by reducing the duration of seizures and delaying the latency of seizures induced by PTZ.

Therapeutic Applications of Terpenes on Inflammatory Diseases

In the last decades, the search for natural products with biological applications as alternative treatments for several inflammatory diseases has increased. In this respect, terpenes are a family of organic compounds obtained mainly from plants and trees, such as tea, cannabis, thyme, and citrus fruits like lemon or mandarin. These molecules present attractive biological properties such as analgesic and anticonvulsant activities. Furthermore, several studies have demonstrated that certain terpenes could reduce inflammation symptoms by decreasing the release of pro-inflammatory cytokines for example, the nuclear transcription factor-kappa B, interleukin 1, and the tumor necrosis factor-alpha. Thus, due to various anti-inflammatory drugs provoking side effects, the search and analysis of novel therapeutics treatments are attractive. In this review, the analysis of terpenes’ chemical structure and their mechanisms in anti-inflammatory functions are addressed. Additionally, we present a general analysis of recent investigations about their applications as an alternative treatment for inflammatory diseases. Furthermore, we focus on terpenes-based nanoformulations and employed dosages to offer a global perspective of the state-of-the-art.

Synthetic aspects of condensed pyrimidine derivatives

: The present review focuses on the synthesis of two heteroatoms containing six-membered heterocyclic compounds, i.e., pyrimidine. In this review, a number of pyrimidine derivatives have been illustrated, which show the exceptional ability towards clinical practices. Pyrimidine derivatives show antimicrobial, antibacterial, antifungal, antiallergic, antiinflammatory, anticancer and anticonvulsant activities. Thus, it encourages the researchers to synthesize the novel, potent, safe and selective pyrimidine derivatives effective against the mutant strains., The development of synthetic protocols is on the high priority in medicinal chemistry research. Many methodologies have been developed for the preparation of pyrimidine derivatives. In this review article, the synthetic strategies of pyrimidine derivatives are classified into metal-catalysed synthesis, ionic-liquid assisted synthesis, microwave-assisted synthesis and solid-phase synthesis.

Panx1 channels promote both anti- and pro-seizure-like activities in the zebrafish via p2rx7 receptors and ATP signaling

The molecular mechanisms of excitation-inhibition imbalances promoting seizure generation in epilepsy patients are not fully understood. Experimental evidence suggests that Pannexin1 (Panx1), an ATP release channel, modulates excitability of the brain. In this report, we have performed behavioral and molecular phenotyping experiments on zebrafish larvae bearing genetic or pharmacological knockouts of panx1a or panx1b channels, each highly homologous to human PANX1. When Panx1a function is lost or both channels are under pharmacological blockage, treatment with pentylenetetrazol to induce seizures causes reduced ictal-like events and seizure-like locomotion. These observations were extended by transcriptome profiling, where a spectrum of distinct metabolic and cell signaling states correlates with the loss of panx1a. The pro- and anticonvulsant activities of both Panx1 channels affects ATP release and involves the purinergic receptor p2rx7. We propose that Panx1 zebrafish models offer opportunities to explore the molecular and physiological basis of seizures and assist anticonvulsant drug discovery.

Medicinal plants with anticonvulsant activities with emphasis on their mechanisms of action

A large percent of the patients were controlled by the available antiepileptic drugs. The limited efficacy of antiepileptic drugs is still a matter of concern, >30% of patients showed refractory epilepsy and 30-40% suffered from antiepileptic side effects. Many kinds of medicinal plants possessed antiepileptic activity, and many researchers have focused on the efficacy of their crude extracts. This review discussed the medicinal plants with antiepileptic effect focusing on active ingredients and their mode of action.

Review Article on Traditional out look of Smilax zeylanica

Since time immemorial plants have been used for various needs such as food, fodder, construction, dyes and medicine. Smilax zeylanica L., belonging to the monocotyledon family Smilacaceae, is a dioecious climbing shrub with woody stem. The plant is used as a substitute for Sarsaparilla. In this review, we present updated information on the ethnobotanical uses, phytochemistry and pharmacological activities shown by S. zeylanica by referring standard flora, journal articles and various search engines. Whole plant or certain parts of the plant (leaf, root, rhizome, fruit and stem) are used ethnobotanically in several countries for several purposes such as fodder, vegetable and in the treatment of diseases like skin diseases, piles, dysentery, venereal diseases, rheumatism, toothache, arthritis, and urinary complaints. The plant is reported to contain many chemicals and diosgenin, smilagenin, β-sitosterol, hydroxytyrosol, squalene and sarsapogenin are few among the important phytochemicals. A number of bioactivities such as antimicrobial, cytotoxic, analgesic, anti-inflammatory, antidepressant, antioxidant, antidiabetic and anticonvulsant activities have been shown by the plant. Overall, it can be concluded that S. zeylanica is a plant which is extensively utilized ethnobotanically for various therapeutic applications and is shown to exhibit a range of bioactivities, the results of which justifies the ethnobotanical uses of the plant. Further, S. zeylanica can be screened for developing bioactive phytochemicals which can be used as lifesaving drugs.