Acetylcholinesterase is a member of the α/β hydrolase protein super family, with a significant role in acetylcholine-mediated neurotransmission. Research in the modulators of AChEs has moved from a ...potent poison (Sarin, Soman) in war times to the potent medicine (physostigmine) in peaceful times. Natural anti-AChE includes carbamates, glycoalkaloids, anatoxins derived from green algae; synthetic anti-AChE includes highly poisonous organophosphates used as nerve gases and insecticides. Recently, the role of anti-AChE was reassessed from neurotoxins to neuron-protective in the diseases characterized by impaired acetylcholine-mediated neurotransmission like Alzheimer's disease (AD). So, the AChE has been proven to be the most viable therapeutic target for the symptomatic treatment of AD. This review article gives a spectrum of strategies to design AChE inhibitors used in the Alzheimer therapy.
Display omitted The role of anti-AChE has been reassessed from neurotoxins to neuron-protective in the diseases characterized by impaired acetylcholine-mediated neurotransmission.
•The pathophysiology of Alzheimer's disease has been discussed.•Role of AChE in AD has been discussed.•This review also includes data regarding AChE inhibitors.
Microalgae biotechnology has recently emerged into the lime light owing to numerous consumer products that can be harnessed from microalgae. Product portfolio stretches from straightforward biomass ...production for food and animal feed to valuable products extracted from microalgal biomass, including triglycerides which can be converted into biodiesel. For most of these applications, the production process is moderately economically viable and the market is developing. Considering the enormous biodiversity of microalgae and recent developments in genetic and metabolic engineering, this group of organisms represents one of the most promising sources for new products and applications. With the development of detailed culture and screening techniques, microalgal biotechnology can meet the high demands of food, energy and pharmaceutical industries. This review article discusses the technology and production platforms for development and creation of different valuable consumer products from microalgal biomass.
A novel series of flavonoid based compounds were designed, synthesized and biologically evaluated for Acetylcholinesterase (AChE) inhibitory activity integrated with advanced glycation end products ...(AGEs) inhibitory and antioxidant potential. Most of the derivatives inhibited AChE in nanomolar IC50 range along with good AGEs inhibitory and radical scavenging activity. Thus, flavonoids might be the promising lead compounds as potential polyfunctional anti-Alzheimer’s agents.
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A novel series of flavonoid based compounds were designed, synthesized and biologically evaluated for Acetylcholinesterase (AChE) inhibitory activity integrated with advanced glycation end products (AGEs) inhibitory and antioxidant potential. Most of the derivatives inhibited AChE in nanomolar IC50 range along with good AGEs inhibitory and radical scavenging activity. Among them, 7m, strongly inhibited AChE (IC50 = 5.87 nM) and found to be potent as compared to the reference drug donepezil (IC50 = 12.7 nM). Its potent inhibitory activity has been justified by docking analysis that revealed its dual binding characteristic with both CAS (catalytic active site) and PAS (peripheral anionic site) of AChE, simultaneously. Additionally, this compound also displayed ability to prevent advanced glycation end products formation (IC50 = 23.0 µM) with additional radical scavenging property (IC50 = 37.12 nM). It (7m) also ameliorated scopolamine induced memory deficit in mice employing Morris water maze test. Thus, flavonoids might be the promising lead compounds as potential polyfunctional anti-Alzheimer’s agents.
► Poultry litter anaerobic digestion effluent (PLDE) diluted into water at 6% (v/v) supported significant algae growth. ► Multiple dosage of PLDE recoded better algae growth relative to single dose. ...► Algae biomass productivity of 76mgL−1d−1 was recorded under booster dosage conditions. ► Average biochemical composition of dry biomass (w/w) was; protein 39%, carbohydrates 22% and lipids 10%. ► Algae removed 60% of total nitrogen and 80% of total phosphorus present in PLDE.
The potential of mixotrophic microalgae to utilize poultry litter anaerobic digester (AD) effluent (PLDE) as nutritional growth medium was evaluated. Three algal strains viz. Chlorella minutissima, Chlorella sorokiniana and Scenedesmus bijuga and their consortium showed significant biomass productivity in 6% (v/v) concentration of PLDE in deionized water. Multiple booster dosage of PLDE supported better growth relative to a single dose PLDE. The maximum biomass productivity of 76mgL−1d−1 was recorded. The biomass was rich in protein (39% w/w) and carbohydrates (22%) while lipids (<10%) were low, making it most suitable as an animal feed supplement. The mixotrophic algae showed sustainable growth against variations in PLDE composition in different AD batches, thus proving to be a suitable candidate for large scale wastewater treatment with concomitant production of renewable biomass feedstock for animal feed and bioenergy applications.
Nutraceuticals are the nourishing components (hybrid of nutrition and pharmaceuticals) that are biologically active and possess capability for maintaining optimal health and benefits. These products ...play a significant role in human health care and its endurance, most importantly for the future therapeutic development. Nutraceuticals have received recognition due to their nutritional benefits along with therapeutic effects and safety profile. Nutraceuticals are globally growing in the field of services such as health care promotion, disease reduction, etc. Various drug nutraceutical interactions have also been elaborated with various examples in this review. Several patents on nutraceuticals in agricultural applications and in various diseases have been stated in the last section of review, which confirms the exponential growth of nutraceuticals’ market value. Nutraceuticals have been used not only for nutrition but also as a support therapy for the prevention and treatment of various diseases, such as to reduce side effects of cancer chemotherapy and radiotherapy. Diverse novel nanoformulation approaches tend to overcome challenges involved in formulation development of nutraceuticals. Prior information on various interactions with drugs may help in preventing any deleterious effects of nutraceuticals products. Nanotechnology also leads to the generation of micronized dietary products and other nutraceutical supplements with improved health benefits. In this review article, the latest key findings (clinical studies) on nutraceuticals that show the therapeutic action of nutraceutical’s bioactive molecules on various diseases have also been discussed.
Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, pose a significant global health challenge, emphasizing the need for novel neuroprotective agents. Basil (Ocimum spp.) has been ...recognized for its therapeutic potential, and numerous studies have reported neuroprotective effects. In this manuscript, we present a computational protocol to extricate the underlying mechanism of action of basil compounds in neuroprotective effects. Molecular docking-based investigation of the chemical interactions between selected bioactive compounds from basil and key neuroprotective targets, including AChE, GSK3β, γ-secretase, and sirtuin2. Our results demonstrate that basil compound myricerone caffeoyl ester possesses a high affinity of −10.01 and −8.85 kcal/mol against GSK3β and γ-secretase, respectively, indicating their potential in modulating various neurobiological processes. Additionally, molecular dynamics simulations were performed to explore the protein–ligand complexes’ stability and to analyze the bound basil compounds’ dynamic behavior. This comprehensive computational investigation enlightens the putative mechanistic basis for the neuroprotective effects of basil compounds, providing a rationale for their therapeutic use in neurodegenerative disorders after further experimental validation.
PROTACs in Treatment of Cancer: A Review Arora, Poonam; Singh, Manjinder; Singh, Varinder ...
Mini reviews in medicinal chemistry,
01/2021, Letnik:
21, Številka:
16
Journal Article
Recenzirano
Cancer treatment has become a major challenge amidst the resistance and relapse caused by the various treatments available. The PROteolysis TAargeting Chimera (PROTAC) technology involves the ...degradation of target protein against the inhibition by small drug molecules. The PROTACs with high potency and activity have been frequently reported; however, no PROTAC acting against cancer has reached the clinical trials. The concept of PROTACs involves the reduction in the disease-causing protein by its degradation through the ubiquitin-proteasomal enzyme system. This concept has attracted a lot of attention from both industry and academia due to its potential in drug discovery (in the form of PROTACs), which can conquer the resistance associated with current treatments of cancer. Thus, it is the need of the hour to identify and synthesize more PROTACs for a viable treatment of cancer. This article reviews the design, activity and effects produced in cancer by some recently developed PROTACs.
Abstract
Efficient, practical syntheses of sorafenib and regorafenib have been achieved in a manner that is free from the problems associated with previously reported methods. The process involved ...preparation of 4-(4-aminophenoxy)-N-methylpicolinamide (sorafenib intermediate) and 4-(4-amino-3-fluorophenoxy)-N-methylpicolinamide (regorafenib intermediate) using only a single base and did not require the use of an inert atmosphere. The reaction of intermediates with phenyl 4-chloro-3-(trifluoromethyl)phenyl carbamate, prepared using water-assisted synthesis of carbamates, was used to install the main urea functionality in these molecules.
No drug on the market, as a single entity, participates in different pathways involved in the pathology of Alzheimer’s disease. The current study is aimed at the exploration of multifunctional ...chalcone derivatives which can act on multiple targets involved in Alzheimer’s disease. A series of novel aminoethyl-substituted chalcones have been developed using in silico approaches (scaffold morphing, molecular docking, and ADME) and reported synthetic methods. The synthesized analogs were characterized and evaluated biologically using different in vitro assays against AChE, AGEs, and radical formation. Among all compounds, compound PS-10 was found to have potent AChE inhibitory activity (IC50 = 15.3 nM), even more than the standard drug (IC50 = 15.68 nM). Further, the in vivo evaluation of PS-10 against STZ-induced dementia in rats showed memory improvement (Morris Water Maze test) in rats. Also, PS-10 inhibited STZ-induced brain AChE activity and oxidative stress, further strengthening the observed in vitro effects. Further, the molecular dynamic simulation studies displayed the stability of the PS-10 and AChE complex. The novel aminoethyl-substituted chalcones might be considered potential multifunctional anti-Alzheimer’s molecules.
High-rate algal ponds have the potential to produce 59T of dry biomass ha−1year−1 based on the specific productivity of 20gm−2day−1. Atmospheric air provides only 5% of the CO2 to the pond surface ...required for photosynthesis. Hence, CO2 is usually provided via bubbling of concentrated CO2-air mixture into the algae ponds. This process is, however, not significantly effective in terms of mass transfer. Use of bubble column to increase the interfacial area of contact available for gas exchange is proposed as an efficient alternative. A carbonation column (CC) was modeled and designed to measure CO2 absorptivity in-pond water at various pH regimes. The CC performed at 83% CO2 transfer efficiency. An air-to-pond mass transport coefficient of 0.0037mmin−1 was derived. The proposed device can be used with any exhaust gas stream with higher concentrations of CO2 in conjunction with raceways for optimizing algae production.
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