Novel hydrazones derived from anthranilic acid as potent cholinesterases and α-glycosidase inhibitors: Synthesis, characterization, and biological effects.

N-substitued anthranilic acid derivatives are commonly found in the structure of many biologically active molecules. In this study, new members of hydrazones derived from anthranilic acid (1-15) were synthesized and investigated their effect on some metabolic enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glycosidase (α-Gly). Results indicated that all the molecules exhibited potent inhibitory effects against all targets as compared to the standard inhibitors, revealed by IC50 values. Ki values of compounds for AChE, BChE, and α-Gly enzymes were obtained in the ranges 66.36 ± 8.30-153.82 ± 13.41, 52.68 ± 6.38-113.86, and 2.13 ± 0.25-2.84 nM, respectively. The molecular docking study was performed for the most active compounds to the determination of ligand-enzyme interactions. Binding affinities of the most active compound were found at the range of -9.70 to -9.00 kcal/mol for AChE, -11.60 to -10.60 kcal/mol for BChE, and -10.30 to -9.30 kcal/mol for α-Gly. Molecular docking simulations showed that the novel compounds had preferential interaction with AChE, BChE, and α-Gly. Drug-likeness properties and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analyzes of all synthesized compounds (1-15) were estimated and their toxic properties were evaluated as well as their therapeutic properties. Moreover, molecular dynamics simulations were carried out to understand the accuracy of the most potent derivatives of docking studies.

Antidiabetic Potential of a Trimeric Anthranilic Acid Peptide Isolated from Malbranchea flocciformis.

Compound 3, a trimeric anthranilic acid peptide, and another three metabolites were isolated from an organic extract from the culture medium of Malbranchea flocciformis ATCC 34530. The chemical structure proposed previously for 3 was unequivocally assigned via synthesis and X-ray diffraction analysis. Tripeptide 3 showed insulinotropic properties by decreasing the postprandial peak in healthy and hyperglycemic mice. It also increased glucose-induced insulin secretion in INS-1E at 5 µM, specifically at higher glucose concentrations. These results revealed that 3 might act as an insulin sensitizer and a non-classical insulin secretagogue. Altogether, these findings are in harmony with the in vivo oral glucose tolerance test and acute oral hypoglycemic assay. Finally, the chemical composition of the extract was established by the Global Natural Products Social Molecular Network platform. Phylogenetic analysis using the internal transcribed spacer region revealed that M. flocciformis ATCC 34530 is related to the Malbrancheaceae.

Synthesis of 2-Amino-N'-aroyl(het)arylhydrazides, DNA Photocleavage, Molecular Docking and Cytotoxicity Studies against Melanoma CarB Cell Lines.

Diacylhydrazine bridged anthranilic acids with aryl and heteroaryl domains have been synthesized as the open flexible scaffold of arylamide quinazolinones in order to investigate flexibility versus rigidity towards DNA photocleavage and sensitivity. Most of the compounds have been synthesized via the in situ formation of their anthraniloyl chloride and subsequent reaction with the desired hydrazide and were obtained as precipitates, in moderate yields. All compounds showed high UV-A light absorption and are eligible for DNA photocleavage studies under this "harmless" irradiation. Despite their reduced UV-B light absorption, a first screening indicated the necessity of a halogen at the p-position in relation to the amine group and the lack of an electron-withdrawing group on the aryl group. These characteristics, in general, remained under UV-A light, rendering these compounds as a novel class of UV-A-triggered DNA photocleavers. The best photocleaver, the compound 9, was active at concentrations as low as 2 µΜ. The 5-Nitro-anthranilic derivatives were inactive, giving the opposite results to their related rigid quinazolinones. Molecular docking studies with DNA showed possible interaction sites, whereas cytotoxicity experiments indicated the iodo derivative 17 as a potent cytotoxic agent and the compound 9 as a slight phototoxic compound.

Characterization of anthranilic acid produced by Virgibacillus salarius MML1918 and its bio-imaging application.

Anthranilic acid (AA) holds significant importance in the chemical industry. It serves as a crucial building block for the amino acid tryptophan by manipulating the tryptophan biosynthesis pathway, it is possible to increase the production of anthranilic acid. In this study, we utilized metabolic engineering approaches to produce anthranilic acid from the halophilic bacterium Virgibacillus salarius MML1918. The halophilic bacteria were grown in an optimized production medium, and mass production of secondary metabolites was made in ATCC medium 1097 Proteose peptone-for halophilic bacteria and subjected to column chromatography followed by sub-column chromatography the single band for the purified compound was confirmed. Further, various spectral analyses were made for the partially purified compounds, and fluorescence microscopy for fungal cell observation was performed. The purified compound was confirmed by single crystal X-ray diffraction (XRD) analysis, and it was identified as 2-amino benzoic acid. The Fourier transform infrared Spectroscopy (FT-IR) spectrum and nuclear magnetic resonance (NMR) spectrum also confirm the structural characteristic of 2-amino benzoic acid. The UV-Vis absorption spectrum of AA shows the maximum absorption at 337.86 nm. The emission spectrum of 2-amino benzoic acid showed the maximum emission at 453 nm. The bio-imaging application of 2-amino benzoic acid was examined with fungal mycelium of Rhizoctonia solani. It was effectively bound and emitted the blue color at the concentration of 200 and 300 µg/mL. The halophilic bacterium (V. salarius), may have unique metabolic pathways and requirements compared to non-halophilic organisms, to produce AA effectively. This could have implications for industrial biotechnology, particularly in manufacturing environments where high salt concentrations are present and also it can be used as bio-imaging agent.

Synthesis of a natural quinoline alkaloid isolated from the deep-sea-derived fungus and its potential as a therapeutic for Parkinson's disease.

2-(Quinoline-8-carboxamido)benzoic acid (2-QBA; 1) is a natural quinoline alkaloid isolated from the deep-sea-derived fungus Aspergillus sp. SCSIO06786. Alkaloid 1 was synthesized by an amidation reaction of 8-quinolinecaroxylic acid with methyl anthranilate, followed by hydrolysis. The neuroprotective properties of 1 were evaluated using a Caenorhabditis elegans Parkinson's disease model, which revealed that 1 significantly ameliorated 1-methyl-4-phenylpyridinium (MPP+)-induced dopaminergic neurodegeneration in a dose-dependent manner. MPP+-induced behavioral defects in worms, including impaired locomotion and basal slowing ability, were restored by treatment with 1. We further demonstrated that treatment with 1 modulates the formation of neurotoxic α-synuclein oligomers by suppressing α-synuclein expressions and enhancing proteasome activity. These results suggest that 1 is a promising therapeutic candidate for the treatment of Parkinson's disease.

Synthesis, Molecular Docking, and Biological Evaluation of Novel Anthranilic Acid Hybrid and Its Diamides as Antispasmodics.

The present article focuses on the synthesis and biological evaluation of a novel anthranilic acid hybrid and its diamides as antispasmodics. Methods: Due to the predicted in silico methods spasmolytic activity, we synthesized a hybrid molecule of anthranilic acid and 2-(3-chlorophenyl)ethylamine. The obtained hybrid was then applied in acylation with different acyl chlorides. Using in silico analysis, pharmacodynamic profiles of the compounds were predicted. A thorough biological evaluation of the compounds was conducted assessing their in vitro antimicrobial, cytotoxic, anti-inflammatory activity, and ex vivo spasmolytic activity. Density functional theory (DFT) calculation, including geometry optimization, molecular electrostatic potential (MEP) surface, and HOMO-LUMO analysis for the synthesized compounds was conducted using the B3LYP/6-311G(d,p) method to explore the electronic behavior, reactive regions, and stability and chemical reactivity of the compounds. Furthermore, molecular docking simulation along with viscosity measurement indicated that the newly synthesized compounds interact with DNA via groove binding mode. The obtained results from all the experiments demonstrate that the hybrid molecule and its diamides inherit spasmolytic, antimicrobial, and anti-inflammatory capabilities, making them excellent candidates for future medications.

Synthesis and Biological Evaluation of New Quinoline and Anthranilic Acid Derivatives as Potential Quorum Sensing Inhibitors.

Inhibiting quorum sensing (QS), a central communication system, is a promising strategy to combat bacterial pathogens without antibiotics. Here, we designed novel hybrid compounds targeting the PQS (Pseudomonas quinolone signal)-dependent quorum sensing (QS) of Pseudomonas aeruginosa that is one of the multidrug-resistant and highly virulent pathogens with urgent need of new antibacterial strategies. We synthesized 12 compounds using standard procedures to combine halogen-substituted anthranilic acids with 4-(2-aminoethyl/4-aminobuthyl)amino-7-chloroquinoline, linked via 1,3,4-oxadiazole. Their antibiofilm activities were first pre-screened using Gram-negative Chromobacterium violaceum-based reporter, which identified compounds 15-19 and 23 with the highest anti-QS and minimal bactericidal effects in a single experiment. These five compounds were then evaluated against P. aeruginosa PAO1 to assess their ability to prevent biofilm formation, eradicate pre-formed biofilms, and inhibit virulence using pyocyanin as a representative marker. Compound 15 displayed the most potent antibiofilm effect, reducing biofilm formation by nearly 50% and pre-formed biofilm masses by 25%. On the other hand, compound 23 exhibited the most significant antivirulence effect, reducing pyocyanin synthesis by over 70%. Thus, our study highlights the potential of 1,3,4-oxadiazoles 15 and 23 as promising scaffolds to combat P. aeruginosa. Additionally, interactive QS systems should be considered to achieve maximal anti-QS activity against this clinically relevant species.

The Cytokines CXCL10 and CCL2 and the Kynurenine Metabolite Anthranilic Acid Accurately Predict Patients at Risk of Developing Dengue With Warning Signs.

BACKGROUND: The resolution or aggravation of dengue infection depends on the patient's immune response during the critical phase. Cytokines released by immune cells increase with the worsening severity of dengue infections. Cytokines activate the kynurenine pathway (KP) and the extent of KP activation then influences disease severity. METHODS: KP metabolites and cytokines in plasma samples of patients with dengue infection (dengue without warning signs [DWS-], dengue with warning signs [DWS+], or severe dengue) were analyzed. Cytokines (interferon gamma [IFN-É£], tumor necrosis factor, interleukin 6, CXCL10/interferon-inducile protein 10 [IP-10], interleukin 18 [IL-18], CCL2/monocyte chemoattractant protein-1 [MCP-1], and CCL4/macrophage inflammatory protein-1beta [MIP-1ß] were assessed by a Human Luminex Screening Assay, while KP metabolites (tryptophan, kynurenine, anthranilic acid [AA], picolinic acid, and quinolinic acid) were assessed by ultra-high-performance liquid chromatography and Gas Chromatography Mass Spectrophotometry [GCMS] assays. RESULTS: Patients with DWS+ had increased activation of the KP where kynurenine-tryptophan ratio, anthranilic acid, and picolinic acid were elevated. These patients also had higher levels of the cytokines IFN-É£, CXCL10, CCL4, and IL-18 than those with DWS-. Further receiver operating characteristic analysis identified 3 prognostic biomarker candidates, CXCL10, CCL2, and AA, which predicted patients with higher risks of developing DWS+ with an accuracy of 97%. CONCLUSIONS: The data suggest a unique biochemical signature in patients with DWS+. CXCL10 and CCL2 together with AA are potential prognostic biomarkers that discern patients with higher risk of developing DWS+ at earlier stages of infection.

Anthranilic Acid Accumulation in Saccharomyces cerevisiae Induced by Expression of a Nonribosomal Peptide Synthetase Gene from Paecilomyces cinnamomeus BCC 9616.

Heterologous expression of nrps33, a nonribosomal peptide synthetase gene, from Paecilomyces cinnamomeus BCC 9616 in Saccharomyces cerevisiae unexpectedly resulted in the accumulation of anthranilic acid, an intermediate in tryptophan biosynthesis. Based on transcriptomic and real-time quantitative polymerase chain reaction (RT-qPCR) results, expression of nrps33 affected the transcription of tryptophan biosynthesis genes especially TRP1 which is also the selectable auxotrophic marker for the expression vector used in this work. The product of nrps33 could inhibit the activity of Trp4 involved in the conversion of anthranilate to N-(5'-phosphoribosyl)anthranilate and therefore caused the accumulation of anthranilic acid. This accumulation could in turn result in down-regulation of downstream tryptophan biosynthesis genes. Anthranilic acid is typically produced by chemical synthesis and has been used as a substrate for synthesising bioactive compounds including commercial drugs; our results could provide a new biological platform for production of this compound.

Biosynthesis of [14 C]-11-De-O-Methyltomaymycin, a Precursor of Radiolabelled Antibody Drug Conjugates.

Antibody drug conjugates (ADCs) are one of the most promising technologies to treat cancer as they combine the specificity of an antibody with the high potency of a cytotoxic molecule such as tomaymycin derivatives, which are DNA-interactive antitumor antibiotics previously isolated from bacterial broth. The multistep chemical synthesis of some tomaymycin derivatives is complicated because their structures contain a reactive imine bond. Therefore, we turned to biosynthesis to obtain 14 C radiolabelled tomaymycin derivative to support ADME studies. Following Hurley's work (J. Antibiotics 1977, 30, 349-370; Antimicrob. Agents Chemother. 1979, 15, 42-45; Acc. Chem. Res. 1980, 13, 263-269), the 14 C radiolabel was incorporated efficiently in one step from radiolabelled tyrosine using the strain Streptomyces sp. FH6421. This process has been further optimized by using anthranilic acid as radiolabelled precursor, leading to one of the highest incorporation levels of radiochemical precursors published to date. This biosynthetic strategy is the fastest way to access such radiolabelled precursors.

Synthesis of the quinazolinone derivatives using an acid-functionalized magnetic silica heterogeneous catalyst in terms of green chemistry.

In this research, the synthesis of the quinazolinone derivatives by the reaction of diaminoglyoxime with anthranilic acid or methyl 2-amino benzoate over an acetic acid-functionalized magnetic silica-based catalyst in water was described. The acetic acid-functionalized catalyst was prepared using a three-step procedure from magnetite NPs that initially coated with a layer of silica through the sol-gel process, modified with an aminosilane layer and functionalized with bromoacetic acid. The catalyst was characterized by means of spectroscopic and microscopic techniques, and its activity was investigated for the synthesis of the quinazolinones, bisquinazolinone and oxadiazole quinazolinones obtained from diaminoglyoxime in water at room temperature.

N-(3',4'-dimethoxycinnamonyl) anthranilic acid alleviates severe acute pancreatitis by inhibiting intestinal barrier dysfunction and NF-κB activation.

Severe acute pancreatitis (SAP) can affect intestinal barrier with a high mortality. To date, effective therapies for SAP are still in urgently need. The purpose of this study was to investigate the role of anthranilic acid active synthetic derivative, N-(3',4'-dimethoxycinnamonyl) anthranilic acid (3,4-DAA), in intestinal barrier dysfunction of SAP. In this study, SAP mice model was induced by caerulein combined with lipopolysaccharide (LPS). SAP mice were pretreated with 3,4-DAA orally. Histological structures of pancreatic and intestinal tissues were observed via hematoxylin-eosin (H&E) staining. Pancreas myeloperoxidase (MPO), serum lipase, and amylase were detected using corresponding kits. Western blot analysis and reverse transcription and quantitative PCR (RT-qPCR) were employed to determine the levels of inflammatory factors in both pancreatic and intestinal tissues. Moreover, the levels of intestinal barrier-related proteins, NLRP3 inflammasome and NF-κB pathway were examined by western blot analysis. Result revealed that 3,4-DAA significantly attenuated pancreas and intestine damage, inhibited the release of inflammatory factors and intestinal barrier dysfunction. Moreover, the expression of NLRP3 and phospho-NF-κB p65 in pancreatic and intestinal tissues was notably suppressed by 3,4-DAA. To sum up, these results demonstrated that 3,4-DAA could ameliorate SAP, partly attributing to the inhibition of intestinal barrier dysfunction and the release of inflammatory factors. These findings may provide a new mechanism support for 3,4-DAA application in the clinical treatment of SAP.

Medicinal chemistry of anthranilic acid derivatives: A mini review.

Anthranilic acid and its analogues present a privileged profile as pharmacophores for the rational development of pharmaceuticals deliberated for managing the pathophysiology and pathogenesis of various diseases. The substitution on anthranilic acid scaffold provides large compound libraries, which enable a comprehensive assessment of the structure activity relationship (SAR) analysis for the identification of hits and leads in a typical drug development paradigm. Besides, their widespread applications as anti-inflammatory fenamates, the amide and anilide derivatives of anthranilic acid analogues play a central role in the management of several metabolic disorders. In addition, these derivatives of anthranilic acid exhibit interesting antimicrobial, antiviral and insecticidal properties, whereas the derivatives based on anthranilic diamide scaffold present applications as P-glycoprotein inhibitors for managing the drug resistance in cancer cells. In addition, the anthranilic acid derivatives serve as the inducers of apoptosis, inhibitors of hedgehog signaling pathway, inhibitors of mitogen activated protein kinase pathway, and the inhibitors of aldo-keto reductase enzymes. The antiviral derivatives of anthranilic acid focus on the inhibition of hepatitis C virus NS5B polymerase to manifest considerable antiviral properties. The anthranilic acid derivatives reportedly present neuroprotective applications by downregulating the key pathways responsible for the manifestation of neuropathological features and neurodegeneration. Nevertheless, the transition metal complexes of anthranilic acid derivatives offer therapeutic applications in diabetes mellitus, and obesity by regulating the activity of α-glucosidase. The present review demonstrates a critical analysis of the therapeutic profile of the key derivatives of anthranilic acid and its analogues for the rational development of pharmaceuticals and therapeutic molecules.

The kynurenine pathway is essential for rhodoquinone biosynthesis in Caenorhabditis elegans.

A key metabolic adaptation of some species that face hypoxia as part of their life cycle involves an alternative electron transport chain in which rhodoquinone (RQ) is required for fumarate reduction and ATP production. RQ biosynthesis in bacteria and protists requires ubiquinone (Q) as a precursor. In contrast, Q is not a precursor for RQ biosynthesis in animals such as parasitic helminths, and most details of this pathway have remained elusive. Here, we used Caenorhabditis elegans as a model animal to elucidate key steps in RQ biosynthesis. Using RNAi and a series of C. elegans mutants, we found that arylamine metabolites from the kynurenine pathway are essential precursors for RQ biosynthesis de novo Deletion of kynu-1, encoding a kynureninase that converts l-kynurenine (KYN) to anthranilic acid (AA) and 3-hydroxykynurenine (3HKYN) to 3-hydroxyanthranilic acid (3HAA), completely abolished RQ biosynthesis but did not affect Q levels. Deletion of kmo-1, which encodes a kynurenine 3-monooxygenase that converts KYN to 3HKYN, drastically reduced RQ but not Q levels. Knockdown of the Q biosynthetic genes coq-5 and coq-6 affected both Q and RQ levels, indicating that both biosynthetic pathways share common enzymes. Our study reveals that two pathways for RQ biosynthesis have independently evolved. Unlike in bacteria, where amination is the last step in RQ biosynthesis, in worms the pathway begins with the arylamine precursor AA or 3HAA. Because RQ is absent in mammalian hosts of helminths, inhibition of RQ biosynthesis may have potential utility for targeting parasitic infections that cause important neglected tropical diseases.

Adaptive laboratory evolution of Pseudomonas putida and Corynebacterium glutamicum to enhance anthranilate tolerance.

Microbial bioproduction of the aromatic acid anthranilate (ortho-aminobenzoate) has the potential to replace its current, environmentally demanding production process. The host organism employed for such a process needs to fulfil certain demands to achieve industrially relevant product levels. As anthranilate is toxic for microorganisms, the use of particularly robust production hosts can overcome issues from product inhibition. The microorganisms Corynebacterium glutamicum and Pseudomonas putida are known for high tolerance towards a variety of chemicals and could serve as promising platform strains. In this study, the resistance of both wild-type strains towards anthranilate was assessed. To further enhance their native tolerance, adaptive laboratory evolution (ALE) was applied. Sequential batch fermentation processes were developed, adapted to the cultivation demands for C. glutamicum and P. putida, to enable long-term cultivation in the presence of anthranilate. Isolation and analysis of single mutants revealed phenotypes with improved growth behaviour in the presence of anthranilate for both strains. The characterization and improvement of both potential hosts provide an important basis for further process optimization and will aid the establishment of an industrially competitive method for microbial synthesis of anthranilate.

Multicomponent Synthesis of Luminescent Iminoboronates.

A family of iminoboronates was prepared through a one-pot multicomponent reaction, starting from boronic acid, anthranilic acid, and different salicylaldehydes. Their synthesis was straightforward and the complexes were obtained in good to excellent yields. Their photophysical properties were assessed in a diluted solution, and the complexes proved to be faintly luminescent. These chelates demonstrated remarkable Aggregation-Induced Emission Enhancement, which was rationalized using crystal structures.

Protective effect of N-(p-amylcinnamoyl) anthranilic acid, phospholipase A2 enzyme inhibitor, and transient receptor potential melastatin-2 channel blocker against renal ischemia-reperfusion injury.

The production of reactive oxygen species and inflammatory events are the underlying mechanisms of ischemia-reperfusion injury (IRI). It was determined that transient receptor potential melastatin-2 (TRPM2) channels and phospholipase A2 (PLA 2 ) enzymes were associated with inflammation and cell death. In this study, we investigated the effect of N-( p-amylcinnamoyl) anthranilic acid (ACA), a TRPM2 channel blocker, and PLA 2 enzyme inhibitor on renal IRI. A total of 36 male Sprague-Dawley rats were divided into four groups: control, ischemia-reperfusion (I/R), I/R + ACA 5 mg, I/R + ACA 25 mg. In I/R applied groups, the ischemia for 45 minutes and reperfusion for 24 hours were applied bilaterally to the kidneys. In the I/R group, serum levels of the blood urea nitrogen (BUN), creatinine, cystatin C (CysC), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 increased. On histopathological examination of renal tissue in the I/R group, the formation of glomerular and tubular damage was seen, and it was detected that there was an increase in the levels of malondialdehyde (MDA), caspase-3, total oxidant status (TOS), and oxidative stress index (OSI); and there was a decrease in total antioxidant capacity (TAC) and catalase enzyme activity. ACA administration reduced serum levels of BUN, creatinine, CysC, KIM-1, NGAL, interleukin-18. In the renal tissue, ACA administration reduced histopathological damage, levels of caspase-3, MDA, TOS, and OSI; and it increased the level of TAC and catalase enzyme activity. It has been shown with the histological and biochemical results in this study that ACA is protective against renal IRI.

A role for the auxin precursor anthranilic acid in root gravitropism via regulation of PIN-FORMED protein polarity and relocalisation in Arabidopsis.

distribution of auxin within plant tissues is of great importance for developmental plasticity, including root gravitropic growth. Auxin flow is directed by the subcellular polar distribution and dynamic relocalisation of auxin transporters such as the PIN-FORMED (PIN) efflux carriers, which can be influenced by the main natural plant auxin indole-3-acetic acid (IAA). Anthranilic acid (AA) is an important early precursor of IAA and previously published studies with AA analogues have suggested that AA may also regulate PIN localisation. Using Arabidopsis thaliana as a model species, we studied an AA-deficient mutant displaying agravitropic root growth, treated seedlings with AA and AA analogues and transformed lines to over-produce AA while inhibiting its conversion to downstream IAA precursors. We showed that AA rescues root gravitropic growth in the AA-deficient mutant at concentrations that do not rescue IAA levels. Overproduction of AA affects root gravitropism without affecting IAA levels. Treatments with, or deficiency in, AA result in defects in PIN polarity and gravistimulus-induced PIN relocalisation in root cells. Our results revealed a previously unknown role for AA in the regulation of PIN subcellular localisation and dynamics involved in root gravitropism, which is independent of its better known role in IAA biosynthesis.

Redox TRPs in diabetes and diabetic complications: Mechanisms and pharmacological modulation.

Transient receptor potential (TRP) channels have shown to be involved in a wide variety of physiological functions and pathophysiological conditions. Modulation of TRP channels reported to play a major role in number of disorders starting from central nervous system related disorders to cardiovascular, inflammatory, cancer, gastrointestinal and metabolic diseases. Recently, a subset of TRP ion channels called redox TRPs gained importance on account of their ability to sense the cellular redox environment and respond accordingly to such redox stimuli. Diabetes, the silent epidemic of the world is increasing at an alarming rate in spite of novel therapeutic interventions. Moreover, diabetes and its associated complications are reported to arise due to a change in oxidative status of cell induced by hyperglycemia. Such a change in cellular oxidative status can modulate the activities of various redox TRP channels (TRPA1, TRPC5, TRPMs and TRPV1). Targeting redox TRPs have potential in diabetes and diabetic complications like neuropathy, cardiomyopathy, retinopathy, cystopathy, and encephalopathy. Thus in this review, we have discussed the activities of different redox sensing TRPs in diabetes and diabetic complications and how they can be modulated pharmacologically, so as to consider them a potential novel therapeutic target in treating diabetes and its comorbidity.

Utility of anthranilic acid and diethylacetylenedicarboxylate for the synthesis of nitrogenous organo/organometallic compounds as urease inhibitors.

Fumarate diester 3 was synthesized upon reacting anthranilic acid with diethylacetylenedicarboxylate. Compound 3 was reacted with different nucleophiles in mild reaction conditions. Selected reaction routes that afforded products 6, 9, 10, 11, and 12 were explained. The estimated mechanism for the reaction of 3 with ethylenediamine to afford 9 was proved by X-ray single-crystal and retro-synthetic reaction. Acetyl anthranilic acid was utilized with zinc and copper to afford the organometallic compounds 14a and 14b, respectively. Three single crystals were afforded for 3, 9 and the organocopper complex 14b. Target compounds were screened for their inhibitory potential against urease enzyme. Most compounds were more potent than thiourea as standard inhibitor, considering that oxopiperazine 9 exhibited double the activity: IC50 = 8.16 ± 0.65 µM (thiourea IC50 = 20.04 ± 0.33 µM). Docking studies were in agreement with the in vitro enzyme assay.