An iboga alkaloid chemotaxonomic marker from endemic Tabernaemontana ternifolia with antitubercular activity

Abstract

Coronaridine (1) was isolated from the CH₂Cl₂ root extract of Tabernaemontana ternifolia. The structure of 1 was established from 1D- and 2D-NMR and HR-ESIMS experiments, and by comparison with reported spectroscopic data. To date, this is the first report of compound 1 from T. ternifolia, introduced as new Tabernaemontana species from Philippines in 2005 on the basis of morphological characters. Coronaridine, an iboga-type indole alkaloid, has been isolated from over 50 Tabernaemontana species and can thus be inferred as a chemotaxonomic marker of the genus. T. ternifolia has a distinct arrangement of leaves not known in the genus, but is variable in other genera. Its isolation from endemic T. ternifolia establishes its position in the genus and supports the claim that coronaridine is a chemical marker of the genus Tabernaemontana. Interestingly, coronaridine exhibited relatively weak activity against Mycobacterium tuberculosis H₃₇Rv (MIC 82.64?μg/mL) (Rifampicin MIC 0.05?μg/mL).     

Stimuli‐Responsive Naphthalene Diimide as Invisible Ink: A Rewritable Fluorescent Platform for Anti‐Counterfeiting

Herein, we report an approach to combat counterfeiting and storage of valuable information based on the solid‐state fluorescence switching behavior of isoniazid functionalized naphthalene diimide (ISO_NDI) in response to an external stimuli (i. e., HCl vapor). The unique feature of ISO_NDI is further utilized to develop an invisible ink (ISO_NDI‐PVA) with commercial polymer polyvinyl alcohol (PVA). A solid‐state fluorescence recovery was observed while loading with HCl vapors. This exclusive property of the material could be applied directly as a security ink for confidential data storage purpose. Based on above strategy, we successfully realized the rewritable application by using ISO_NDI‐PVA ink and confirm its practical efficacy on various substrates by creating different patterns. The solid‐state fluorescence switching behavior of ISO_NDI‐PVA ink exhibited reversible on/off signal for multiple cycles under the influence of HCl/NH₃ vapors. Mechanistic investigation supports a clear participation of intermolecular charge transfer (ICT) phenomenon in the solid‐state fluorescence switching property. The ease of fabricating the ink with invisible to visible characteristics in response to HCl vapors provides new opportunities for exploring the application of ISO_NDI‐PVA as invisible ink for targeted security applications.     

Biological and Cheminformatics Studies of Newly Designed Triazole Based Derivatives as Potent Inhibitors against Mushroom Tyrosinase

A series of nine novel 1,2,4-triazole based compounds were synthesized through a multistep reaction pathway and their structures were scrutinized by using spectral methods such as FTIR, LC-MS, 1H NMR, and 13C NMR. The synthesized derivatives were screened for inhibitory activity against the mushroom tyrosinase and we found that all the synthesized compounds demonstrated decent inhibitory activity against tyrosinase. However, among the series of compounds, N-(4-fluorophenyl)-2-(5-(2-fluorophenyl)-4-(4-fluorophenyl)-4H-1,2,4-triazol-3-ylthio) acetamide exhibited more prominent activity when accompanied with the standard drug kojic acid. Furthermore, the molecular docking studies identified the interaction profile of all synthesized derivatives at the active site of tyrosinase. Based on these results, N-(4-fluorophenyl)-2-(5-(2-fluorophenyl)-4-(4-fluorophenyl)-4H-1,2,4-triazol-3-ylthio) acetamide could be used as a novel scaffold to design some new drugs against melanogenesis.     

A Comprehensive Review on Therapeutic Perspectives of Phytosterols in Insulin Resistance: A Mechanistic Approach

Natural products in the form of functional foods have become increasingly popular due to their protective effects against life-threatening diseases, low risk of adverse effects, affordability, and accessibility. Plant components such as phytosterol, in particular, have drawn a lot of press recently due to a link between their consumption and a modest incidence of global problems, such as Type 2 Diabetes mellitus (T2DM), cancer, and cardiovascular disease. In the management of diet-related metabolic diseases, such as T2DM and cardiovascular disorders, these plant-based functional foods and nutritional supplements have unquestionably led the market in terms of cost-effectiveness, therapeutic efficacy, and safety. Diabetes mellitus is a metabolic disorder categoriszed by high blood sugar and insulin resistance, which influence major metabolic organs, such as the liver, adipose tissue, and skeletal muscle. These chronic hyperglycemia fallouts result in decreased glucose consumption by body cells, increased fat mobilisation from fat storage cells, and protein depletion in human tissues, keeping the tissues in a state of crisis. In addition, functional foods such as phytosterols improve the body’s healing process from these crises by promoting a proper physiological metabolism and cellular activities. They are plant-derived steroid molecules having structure and function similar to cholesterol, which is found in vegetables, grains, nuts, olive oil, wood pulp, legumes, cereals, and leaves, and are abundant in nature, along with phytosterol derivatives. The most copious phytosterols seen in the human diet are sitosterol, stigmasterol, and campesterol, which can be found in free form, as fatty acid/cinnamic acid esters or as glycosides processed by pancreatic enzymes. Accumulating evidence reveals that phytosterols and diets enriched with them can control glucose and lipid metabolism, as well as insulin resistance. Despite this, few studies on the advantages of sterol control in diabetes care have been published. As a basis, the primary objective of this review is to convey extensive updated information on the possibility of managing diabetes and associated complications with sterol-rich foods in molecular aspects.     

An Update on Synthesis of Coumarin Sulfonamides as Enzyme Inhibitors and Anticancer Agents

Coumarin is an important six-membered aromatic heterocyclic pharmacophore, widely distributed in natural products and synthetic molecules. The versatile and unique features of coumarin nucleus, in combination with privileged sulfonamide moiety, have enhanced the broad spectrum of biological activities. The research and development of coumarin, sulfonamide-based pharmacology, and medicinal chemistry have become active topics, and attracted the attention of medicinal chemists, pharmacists, and synthetic chemists. Coumarin sulfonamide compounds and analogs as clinical drugs have been used to cure various diseases with high therapeutic potency, which have shown their enormous development value. The diversified and wide array of biological activities such as anticancer, antibacterial, anti-fungal, antioxidant and anti-viral, etc. were displayed by diversified coumarin sulfonamides. The present systematic and comprehensive review in the current developments of synthesis and the medicinal chemistry of coumarin sulfonamide-based scaffolds give a whole range of therapeutics, especially in the field of oncology and carbonic anhydrase inhibitors. In the present review, various synthetic approaches, strategies, and methodologies involving effect of catalysts, the change of substrates, and the employment of various synthetic reaction conditions to obtain high yields is cited.     

X-ray determination of thermal expansion of Na(ClO3)x(BrO3)1−x mixed crystals

Lattice constants of sodium chlorate and sodium bromate and their mixed crystals were determined over the temperature range from room temperature to 320 °C. The observed lattice constants for the various compositions show strong deviations from those expected from Vegard's rule. The lattice constants at various temperatures were fitted to polynomials of type a = a₀ + a₁t + a₂t². The linear coefficients of expansion for the Na(ClO₃)_x · (BrO₃)_1−x series varies non-linearly with composition showing negative deviations from linearity.     

Graphene-Oxide-Based Fluoro- and Chromo-Genic Materials and Their Applications

Composite materials and their applications constitute a hot field of research nowadays due to the fact that they comprise a combination of the unique properties of each component of which they consist. Very often, they exhibit better performance and properties compared to their combined building blocks. Graphene oxide (GO), as the most widely used derivative of graphene, has attracted widespread attention because of its excellent properties. Abundant oxygen-containing functional groups on GO can provide various reactive sites for chemical modification or functionalization of GO, which in turn can be used to develop novel GO-based composites. This review outlines the most recent advances in the field of novel dyes and pigments encompassing GO as a key ingredient or as an important cofactor. The interactions of graphene with other materials/compounds are highlighted. The special structure and unique properties of GO have a great effect on the performance of fabricated hybrid dyes and pigments by enhancing the color performance of dyes, the anticorrosion properties of pigments, the viscosity and rheology of inks, etc., which further expands the applications of dyes and pigments in dyeing, optical elements, solar-thermal energy storage, sensing, coatings, and microelectronics devices. Finally, challenges in the current development as well as the future prospects of GO-based dyes and pigments are also discussed. This review provides a reference for the further exploration of novel dyes and pigments.     

Natural Polyphenols for the Preservation of Meat and Dairy Products

Food spoilage makes foods undesirable and unacceptable for human use. The preservation of food is essential for human survival, and different techniques were initially used to limit the growth of spoiling microbes, e.g., drying, heating, salting, or fermentation. Water activity, temperature, redox potential, preservatives, and competitive microorganisms are the most important approaches used in the preservation of food products. Preservative agents are generally classified into antimicrobial, antioxidant, and anti-browning agents. On the other hand, artificial preservatives (sorbate, sulfite, or nitrite) may cause serious health hazards such as hypersensitivity, asthma, neurological damage, hyperactivity, and cancer. Thus, consumers prefer natural food preservatives to synthetic ones, as they are considered safer. Polyphenols have potential uses as biopreservatives in the food industry, because their antimicrobial and antioxidant activities can increase the storage life of food products. The antioxidant capacity of polyphenols is mainly due to the inhibition of free radical formation. Moreover, the antimicrobial activity of plants and herbs is mainly attributed to the presence of phenolic compounds. Thus, incorporation of botanical extracts rich in polyphenols in perishable foods can be considered since no pure polyphenolic compounds are authorized as food preservatives. However, individual polyphenols can be screened in this regard. In conclusion, this review highlights the use of phenolic compounds or botanical extracts rich in polyphenols as preservative agents with special reference to meat and dairy products.     

Plumbagin Alleviates Intracerebroventricular-Quinolinic Acid Induced Depression-like Behavior and Memory Deficits in Wistar Rats

Plumbagin, a hydroxy-1,4-naphthoquinone, confers neuroprotection via antioxidant and anti-inflammatory properties. The present study aimed to assess the effect of plumbagin on behavioral and memory deficits induced by intrahippocampal administration of Quinolinic acid (QA) in male Wistar rats and reveal the associated mechanisms. QA (300 nM/4 μL in Normal saline) was administered i.c.v. in the hippocampus. QA administration caused depression-like behavior (forced swim test and tail suspension tests), anxiety-like behavior (open field test and elevated plus maze), and elevated anhedonia behavior (sucrose preference test). Furthermore, oxidative–nitrosative stress (increased nitrite content and lipid peroxidation with reduction of GSH), inflammation (increased IL-1β), cholinergic dysfunction, and mitochondrial complex (I, II, and IV) dysfunction were observed in the hippocampus region of QA-treated rats as compared to normal controls. Plumbagin (10 and 20 mg/kg; p.o.) treatment for 21 days significantly ameliorated behavioral and memory deficits in QA-administered rats. Moreover, plumbagin treatment restored the GSH level and reduced the MDA and nitrite level in the hippocampus. Furthermore, QA-induced cholinergic dysfunction and mitochondrial impairment were found to be ameliorated by plumbagin treatment. In conclusion, our results suggested that plumbagin offers a neuroprotective potential that could serve as a promising pharmacological approach to mitigate neurobehavioral changes associated with neurodegeneration.     

Ferroptosis: A New Road towards Cancer Management

Ferroptosis is a recently described programmed cell death mechanism that is characterized by the buildup of iron (Fe)-dependent lipid peroxides in cells and is morphologically, biochemically, and genetically distinct from other forms of cell death, having emerged to play an important role in cancer biology. Ferroptosis has significant importance during cancer treatment because of the combination of factors, including suppression of the glutathione peroxidase 4 (Gpx4), cysteine deficiency, and arachidonoyl (AA) peroxidation, which cause cells to undergo ferroptosis. However, the physiological significance of ferroptosis throughout development is still not fully understood. This current review is focused on the factors and molecular mechanisms with the diagrammatic illustrations of ferroptosis that have a role in the initiation and sensitivity of ferroptosis in various malignancies. This knowledge will open a new road for research in oncology and cancer management.