Antibacterial and antioxidant assay of novel heteroaryl-substituted methane derivatives synthesized via ceric ammonium nitrate (CAN) catalyzed one-pot green approach.

Individually, hydroxycoumarin and amino pyrimidine derivatives are of significant biological interest owing to their importance in drugs and pharmaceuticals. To access their combined biological impact into one molecule, we designed a novel, one-pot green approach for synthesizing trisubstituted methanes. A series of new heteroaryl-substituted methanes have been synthesized and subjected to in vitro antibacterial and antioxidant evaluation. Tests against clinical isolates of Escherichia coli (gram-negative) and Staphylococcus aureus showed potent activity of the derivatives 4a, 4b, 4d, 4e, 4f, 4l, and 5 against the former, and 4a, 4e, 4j, and 4l against the later one. Further, antioxidant assay for these TRSMs was also studied where 4a, 4b, 4f, 4j, and 4l exhibited the most promising results. These preliminary bioassay evaluations strongly suggest the promise and scope of these molecules in medical science. A one pot methodology for the synthesis of coumarin and uracil tethered trisubstituted methanes has been reported. The synthesized derivatives were further analyzed for their antibacterial and antioxidant properties to explore their medicinal applications. The salient features of this methodology are operational simplicity, short reaction time, good to moderate yields of the products, easy purification method. Biochemical assay of the synthesized TRSMs a reveals their utility in medicinal & pharma industry.

Regioselective synthesis of pyrimidine-fused tetrahydropyridines and pyridines by microwave-assisted one-pot reaction.

A regioselective three-component reaction of α,ß-unsaturated aldehydes, cyclic 1,3-dicarbonyls and 6-aminouracils in the presence of FeCl3·6H2O as catalyst under microwave irradiation has been demonstrated. Three-component reaction of α,ß-unsaturated aldehydes like cinnamaldehyde/crotonaldehyde, cyclic 1,3-diketones such as 2-hydroxy-1,4-naphthaquinone/dimedone and 6-aminouracils provides regioselective pyrimidine-fused tetrahydropyridines tethered with cyclic 1,3-diketones. On the other hand, replacing cyclic 1,3-diketones by 4-hydroxycoumarin and keeping all other conditions the same provided a two-component pyrimidine-fused pyridines. The salient features of this methodology are operational simplicity, short reaction time, good-to-moderate yields of the products, easy purification method and regioselective products having medicinally important heterocyclic rings such as pyrimidine, tetrahydropyridine or pyridine.

Synthesis of aminouracil-tethered tri-substituted methanes in water by iodine-catalyzed multicomponent reactions.

An efficient, mild and environmentally benign protocol has been developed for the synthesis of aminouracil-tethered tri-substituted methane derivatives. The three-component reaction of 2-hydroxy-1,4-naphthaquinone, 6-amino-1,3-dimethyluracil and aldehydes in the presence of molecular iodine as catalyst under reflux conditions resulted in aminouracil-tethered tri-substituted methane derivatives 4 in aqueous medium. Similarly, the four-component reaction of 2-hydroxy-1,4-naphthaquinone, o-phenylenediamine, aldehydes and aminouracil derivatives resulted in aminouracil-tethered tri-substituted methane derivatives 6 under the same reaction conditions. The notable features of this protocol are simple experimental procedure, cheap catalyst, readily available starting materials, moderate-to-good yields of the products having biologically active important moieties such as aminouracil, hydroxy-naphthaquinone/benzophenazine.

Multicomponent synthesis of diverse pyrano-fused benzophenazines using bifunctional thiourea-based organocatalyst in aqueous medium.

A series of pyrano-fused benzophenazines were synthesized using a bifunctional thiourea-based organocatalyst from the one-pot four-component reaction of 2-hydroxy-1,4-naphthoquinone, benzene-1,2-diamines, malononitrile or its derivatives and isatins or aromatic aldehydes in aqueous medium. Metal-free reaction condition, water as solvent, high bond forming efficiency (five new bonds formed in one step), good yields and easy purification process are the notable features of this methodology.

Recent Advancement in Multicomponent Synthesis of Fused Coumarin Derivatives.

The synthesis of coumarin derivatives has been an essential topic since its discovery in 1820. In bioactive compounds, the coumarin moiety serves as a backbone, as many such bioactive compounds with the coumarin moiety play a significant role in their bioactivities. Given this moiety's relevance, several researchers are developing fused-coumarin derivatives to create new drugs. Mostly the approach done for this purpose was a multicomponent reaction based. Over the years, the multicomponent reaction has gained enormous popularity, and this approach has evolved as a replacement for conventional synthetic methods. Because of all these perspectives, we have reported the various fused-coumarin derivatives synthesized using multicomponent reactions in recent years.

Multifactorial role of nanoparticles in alleviating environmental stresses for sustainable crop production and protection.

In the era of dire environmental fluctuations, plants undergo several stressors during their life span, which severely impact their development and overall growth in negative aspects. Abiotic stress factors, especially moisture stress i.e shortage (drought) or excess (flooding), salinity, temperature divergence (i.e. heat and cold stress), heavy metal toxicity, etc. create osmotic and ionic imbalance inside the plant cells, which ultimately lead to devastating crop yield, sometimes crop failure. Apart from the array of abiotic stresses, various biotic stress caused by pathogens, insects, and nematodes also affect production. Therefore, to combat these major challenges in order to increase production, several novel strategies have been adapted, among which the use of nanoparticles (NPs) i.e. nanotechnology is becoming an emerging tool in various facets of the current agriculture system, nowadays. This present review will elaborately depict the deployment and mechanisms of different NPs to withstand these biotic and abiotic stresses, along with a brief overview and indication of the future research works to be oriented based on the steps provided for future research in advance NPs application through the sustainable way.

Recent Advancement in the One-pot Synthesis of the Tri-substituted Methanes (TRSMs) and their Biological Applications.

The history of tri-substituted methanes (TRSMs) in chemical industries is much older. Tri-substituted methanes were previously used as dyes in the chemical industries. Still, there is a significant surge in researchers' interest in them due to their wide range of bioactivities. Trisubstituted methane derivatives show a wide range of biological activities like anti-tumor, antimicrobial, antibiofilm, antioxidant, anti-inflammatory, anti-arthritic activities. Due to the wide range of medicinal applications shown by tri-substituted methanes, most of the methodologies reported in the literature for the synthesis of TRSMs are focused on the one-pot method. This review explored the recently reported one-pot processes for synthesizing trisubstituted methanes and their various medicinal applications. Based on the substitution attached to the -CH carbon, this review categorizes them into two major classes: (I) symmetrical and (II) unsymmetrical trisubstituted methanes. In addition, this review gives an insight into the growing opportunities for the construction of trisubstituted scaffolds via one-pot methodologies. To the best of our knowledge, no one has yet reported a review on the one-pot synthesis of TRSMs. Therefore, here we present a brief literature review of the synthesis of both symmetrical and unsymmetrical TRSMs covering various one-pot methodologies along with their medicinal applications.

Tryptophan-kynurenine pathway attenuates ß-catenin-dependent pro-parasitic role of STING-TICAM2-IRF3-IDO1 signalosome in Toxoplasma gondii infection.

Recent studies have documented the diverse role of host immunity in infection by the protozoan parasite, Toxoplasma gondii. However, the contribution of the ß-catenin pathway in this process has not been explored. Here, we show that AKT-mediated phosphorylated ß-catenin supports T. gondii multiplication which is arrested in the deficiency of its phosphorylation domain at S552 position. The ß-catenin-TCF4 protein complex binds to the promoter region of IRF3 gene and initiates its transcription, which was also abrogated in ß-catenin knockout cells. TBK-independent phosphorylation of STING(S366) and its adaptor molecule TICAM2 by phospho-AKT(T308S473) augmented downstream IRF3-dependent IDO1 transcription, which was also dependent on ß-catenin. But, proteasomal degradation of IDO1 by its tyrosine phosphorylation (at Y115 and Y253) favoured parasite replication. In absence of IDO1, tryptophan was catabolized into melatonin, which supressed cellular reactive oxygen species (ROS) and boosted parasite growth. Conversely, when tyrosine phosphorylation was abolished by phosphosite mutations, IDO1 escaped its ubiquitin-mediated proteasomal degradation system (UPS) and the stable IDO1 prevented parasite replication by kynurenine synthesis. We propose that T. gondii selectively utilizes tryptophan to produce the antioxidant, melatonin, thus prolonging the survival of infected cells through functional AKT and ß-catenin activity for better parasite replication. Stable IDO1 in the presence of IFN-γ catabolized tryptophan into kynurenine, promoting cell death by suppressing phospho-AKT and phospho-ß-catenin levels, and circumvented parasite replication. Treatment of infected cells with kynurenine or its analogue, teriflunomide suppressed kinase activity of AKT, and phosphorylation of ß-catenin triggering caspase-3 dependent apoptosis of infected cells to inhibit parasite growth. Our results demonstrate that ß-catenin regulate phosphorylated STING-TICAM2-IRF3-IDO1 signalosome for a cell-intrinsic pro-parasitic role. We propose that the downstream IRF3-IDO1-reliant tryptophan catabolites and their analogues can act as effective immunotherapeutic molecules to control T. gondii replication by impairing the AKT and ß-catenin axis.