Central Nervous System Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Central Nervous System Agents) - Volume 19, Issue 2, 2019

Introduction: Neurodegenerative diseases (NDDs) are progressive, directly affecting the central nervous system (CNS), the most common and recurrent are Alzheimer's disease (AD) and Parkinson's disease (PD). One factor frequently mentioned in the etiology of NDDs is the generation of free radicals and oxidative stress, producing cellular damages. Studies have shown that the consumption of foods rich in polyphenols, especially those of the flavonoid class, has been related to the low risk in the development of several diseases. Due to the antioxidant properties present in the food, a fruit that has been gaining prominence among these foods is the Euterpe oleracea Mart. (açaí), because it presents in its composition significant amounts of a subclass of the flavonoids, the anthocyanins. Methods: In the case review, the authors receive a basic background on the most common NDDs, oxidative stress and antioxidants. In addition, revisiting the various studies related to NDDs, including flavonoids and consumption of açaí. Results: Detailed analysis of the recently reported case studies reveal that dietary consumption of flavonoid-rich foods, such as açaí fruits, suggests the efficacy to attenuate neurodegeneration and prevent or reverse the age-dependent deterioration of cognitive function. Conclusion: This systematic review points out that flavonoids presenting in açaí have the potential for the treatment of diseases such as PD and AD and are candidates for drugs in future clinical research. However, there is a need for in vitro and in vivo studies with polyphenol that prove and ratify the therapeutic potential of this fruit for several NDDs.

Acrylamide is widely found in baked and fried foods, produced in large amount in industries and is a prime component in toxicity. This review highlights various toxicities that are induced due to acrylamide, its proposed mode of action including oxidative stress cascades and ameliorative mechanisms using phytochemicals. Acrylamide formation, the mechanism of toxicity and the studies on the role of oxidative stress and mitochondrial dysfunctions are elaborated in this paper. The various types of toxicities caused by Acrylamide and the modulation studies using phytochemicals that are carried out on various type of toxicity like neurotoxicity, hepatotoxicity, cardiotoxicity, immune system, and skeletal system, as well as embryos have been explored. Lacunae of studies include the need to explore methods for reducing the formation of acrylamide in food while cooking and also better modulators for alleviating the toxicity and associated dysfunctions along with identifying its molecular mechanisms.

Natural compounds extracted from organisms and microorganisms are an important resource for the development of drugs and bioactive molecules. Many such compounds have made valuable contributions in diverse fields such as human health, pharmaceutics and industrial applications. Presently, however, research on investigating natural compounds from marine organisms is scarce. This is somewhat surprising considering that the marine environment makes a major contribution to Earth's ecosystems and consequently possesses a vast storehouse of diverse marine species. Interestingly, of the marine bioactive natural compounds identified to date, many are venoms, coming from Cnidarians (jellyfish, sea anemones, corals). Cnidarians are therefore particularly interesting marine species, producing important biological compounds that warrant further investigation for their development as possible therapeutic agents. From an experimental aspect, this review aims to emphasize and update the current scientific knowledge reported on selected biological activity (antiinflammatory, antimicrobial, antitumoral, anticoagulant, along with several less studied effects) of Cnidarian venoms/extracts, highlighting potential aspects for ongoing research towards their utilization in human therapeutic approaches.

Background: Aging is a common and inevitable stage in the life cycle of higher organisms. Different organs, including the central nervous system, are affected by aging in different ways. Many processes are involved in aging, and neurodegeneration is one of the aging processes in which the central nervous system is engaged. Brain degeneration during normal aging underlies cognitive disorders experienced by older people. Not all molecular mechanisms associated with age-related neurodegeneration are fully understood; however, there is a whole range of data on the participation of nicotinic acetylcholine receptors in the processes of aging and neurodegeneration. Two main subtypes of nicotinic acetylcholine receptor α7 and α4β2 present in the central nervous system are affected by these processes. The loss of these receptor subtypes during normal aging is one of the reasons for the cognitive impairments. The decrease in nicotinic acetylcholine receptors is also very important for the pathogenesis of age-related neurodegenerative diseases. Thus, the drugs enhancing receptor functions may be considered promising for the treatment of cognitive dysfunction in the aged people. Conclusion: To achieve healthy longevity, the molecular processes that occur during aging should be established. In this regard, the participation and role of nicotinic acetylcholine receptors in the brain aging and degeneration are considered in this review.

Objective: The present study was designed to investigate the potential of Pistacia vera (P. vera) fruits in experimental memory impairments in mice. Material & Methods: Memory impairment was induced in Swiss Albino mice by scopolamine (0.4mg mg/kg. i.p). Animals were divided into five separate groups of six animals each, positive control group received carboxy methyl cellulose (CMC) as vehicle, negative control group received scopolamine with vehicle, and standard group received donepezil (5mg/kg i.p) with Scopolamine. Ethanolic extract of P. vera (EEPV) at doses of 200mg/kg & 400mg/kg p.o were administered to group test1 & test 2 respectively along with scopolamine. Elevated plus maze (EPM), passive avoidance paradigms and morris water maze (MWM) were used as exteroceptive behavioral models to access learning and memory activity. Transfer latency, step down latency and escape latency parameters were evaluated plus maze, passive avoidance paradigm, morris water maze. Thereafter lipid peroxidation test, glutathione level and catalase activities were estimated in homogenized brain of mice. Results: Pretreatment of mice with EEPV (200mg/kg & 400mg/kg) significantly reduced scopolamine induced amnesia. The obtained data clearly revealed that there was increase in escape latency in MWM and also increase in step down latency in passive avoidance paradigm. Transfer latencey was found to be decrease in EPM and biochemical. Parameters were clearly satisfied the data as compared to negative control group which was indicative of cognitive improvement. Conclusion: P. vera fruit extract demonstrated to improve cognitive process by enhancing memory in different experimental paradigm such as EPM, passive avoidance and MWM when administered orally. Hence it would be worthwhile to explore the potential of this plant in the management of memory disorders.

Background: The most effective symptomatic treatment of Parkinson’s disease remains the metabolic precursor of dopamine, L-dopa. To enhance the efficacy of L-dopa, it is often combined with inhibitors of the enzymes, catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) B, key metabolic enzymes of L-dopa and dopamine. Objective: This study attempted to discover compounds that exhibit dual inhibition of COMT and MAO-B among a library of 40 structurally diverse natural compounds. Such dual acting inhibitors may be effective as adjuncts to L-dopa and offer enhanced value in the management of Parkinson’s disease. Methods: Selected natural compounds were evaluated as in vitro inhibitors of rat liver COMT and recombinant human MAO. Reversibility of MAO inhibition was investigated by dialysis. Results: Among the natural compounds morin (IC50 = 1.32 μM), chlorogenic acid (IC50 = 6.17 μM), (+)-catechin (IC50 = 0.86 μM), alizarin (IC50 = 0.88 μM), fisetin (IC50 = 5.78 μM) and rutin (IC50 = 25.3 μM) exhibited COMT inhibition. Among these active COMT inhibitors only morin (IC50 = 16.2 μM), alizarin (IC50 = 8.16 μM) and fisetin (IC50 = 7.33 μM) were noteworthy MAO inhibitors, with specificity for MAO-A. Conclusion: None of the natural products investigated here are dual COMT/MAO-B inhibitors. However, good potency COMT inhibitors have been identified, which may serve as leads for future development of COMT inhibitors.

Background: Approach for green chemistry for chemical synthesis is found to be very efficient as it makes the reaction more easily, less tedious, maximize desired products and minimize by-products. Materials & Methods: Utilizing this approach 1, 5-benzodiazepines and its derivatives have been synthesized and evaluated for skeletal muscle and antianxiety activity. 1, 5-benzodiazepine derivatives have attracted great attention due to its diversity of pharmacological activities and its application in heterocyclic synthesis and medicines. The target compounds were synthesized by first reacting o-phenylenediamine with acetophenone to yield 1, 5-benzodiazepines. In the next step the NH of 1, 5-benzodiazepines were chloroacetylated and then the chloro group was substituted with different anilines. The structures were confirmed on the basis of their TLC, IR, 1H NMR and CHN elemental studies. The physicochemical parameters were determined for BBB penetration through online software. Results: The Log P values of the compounds tested showed that compounds have the potential to be CNS active. The compounds were evaluated for the skeletal muscle relaxant activity and antianxiety activity. It was investigated that 1, 5-benzodiazepines derivatives possess significant differences between control group and treated group. Conclusion: Among these derivatives, the compound bearing chloro group possesses the highest skeletal muscle relaxant and antianxiety activity.