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BACKGROUND: The Maillard reaction involves the interaction of various amino acids and reducing sugars, resulting in food browning. It often produces appealing aromas and flavors. The complexities of the reaction are such that it can be challenging to identify the often numerous and frequently volatile products formed by it. In the present study, we sought to identify and evaluate an unusual product with anti‐oxidant activity arising from a fructose‐histidine Maillard reaction model. The anti‐oxidant profile of this product was assessed by computational means. RESULTS: The fructose‐histidine Maillard reaction products (FH‐MRPs) were generated by heating a 2:1 mixture of the sugar and the amino acid at 140 °C for 2 h. Chromatographically separable fractions, labelled DM‐1 to DM‐8, were obtained using silica gel as the stationary phase and dichloromethane/methanol (DCM/MeOH) mixtures as the mobile one. Fraction DM‐5 exhibited the highest 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging activity, and further bio‐assay guided fractionation led to isolation and identification of 1‐(1H‐imidazo[4,5‐c]pyridin‐4‐yl)ethenone (IMPE) as the active principal, the structure of which was established by nuclear magnetic resonance (NMR) spectroscopic and mass spectral techniques. A mechanism for the formation of IMPE from its precursors is proposed. Density functional theory (DFT) calculations suggest this novel heterocyclic compound exerts its anti‐oxidant effects by interacting with DPPH and 2,2'‐Azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) radicals. Essentially, IMPE was non‐toxic below 300 ug mL−1, showing a concentration‐dependent free radical clearance capacity and reducing power within the 100–1000 μg mL−1 range, and moreover, exhibiting significant Fe2+ chelating abilities wihin the 50‐200 μg mL−1 range. CONCLUSION: This study identified the unique FH‐MRP, IMPE, and found that it acts as food antioxidant through the chelation of metal ions. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

We present a visible light-mediated dual C–H sulfenylation of imidazopyridines using thiocyanate salt as a sulfur source. This method achieves regioselective thiocyanation of imidazopyridines, which are subsequently converted to bis(imidazopyridine)disulfanes upon base treatment. The disulfides are further transformed into thioethers via nucleophilic attack of indoles, azaindole, benzothiazole, and additional imidazopyridines. The antioxidant properties of selected imidazopyridine derivatives were assessed using the DPPH assay, demonstrating notable potential for therapeutic applications. [ABSTRACT FROM AUTHOR]

Imidazo[1,2-a]pyridines and especially their amide derivatives exhibit a wide range of favourable pharmacological properties. In this work, Pd-catalysed carbonylation was used for the first time for the introduction of the carboxamide moiety into positions 6 or 8. A recyclable Pd catalyst, with palladium immobilised on a supported ionic liquid phase decorated with pyridinium ions, was used efficiently for the conversion of 6- or 8-iodo derivatives to the products. In the case of 6-iodo derivatives, a competing mono- and double carbonylation could be observed in the reactions of aliphatic amines as nucleophiles, but under the proper choice of reaction conditions, good-to-excellent selectivities could be achieved towards either the corresponding amides or α-ketomides. The heterogeneous catalyst showed excellent recyclability and low Pd-leaching. [ABSTRACT FROM AUTHOR]

Indolizines and imidazo[1,2‐a]pyridines are commonly found in natural products, synthetic drugs, and bioactive molecules. These two types of derivatives possess good antibacterial, antiparasitic, anticancer activities, and so on. The functionalization of indolizines and imidazo[1,2‐a]pyridines has always been a hot topic in organic chemistry research and has made significant progress. In recent years, our group has been dedicated to developing diverse synthetic methods for the preparation of such important compounds. 1) We have developed diverse C−H functionalization reactions for efficient modification of the parent indolizines and imidazo[1,2‐a]pyridines. 2) A variety of cycloaddition reactions were established for the construction of indolizine and imidazo[1,2‐a]pyridine derivatives from simple raw materials. 3) We have developed intriguing deconstruction‐functionalization reactions of indolizines, enabling the reorganization of heterocyclic frameworks. This paper outlines our group's latest advancements in constructing structurally diverse indolizine and imidazo[1,2‐a]pyridine derivatives. We hope that this work will offer valuable insights and inspiration for the ongoing research in the field of N‐heterocyclic compounds. [ABSTRACT FROM AUTHOR]

ABSTRACT Here, we have succeeded in developing an eco‐efficient, mild, and metal‐free synthetic protocol for biologically significant scaffolds: imidazopyridines and their derivatives via radical cyclization from a wide variety of simple 2‐aminopyridines and phenacyl bromides as reactants and utilizing visible light as a reaction promoter in the ethanol/water solvent. To the best of our knowledge, the present strategy is the first example of visible light promoted synthesis of imidazo[1,2‐a]pyridine via the formation of C‐N bonds. The proposed methodology has various advantages namely quick reaction time, low cost, simple setup, high atom efficiency, easy‐availability of reactants and non‐involvement of specific glasswares and photo reactor system. [ABSTRACT FROM AUTHOR]

An ultrasound-assisted expedient protocol has been developed for the synthesis of imidazo[1,2- a ]pyridines and imidazo[2,1- b ]thiazoles by the C–H functionalization of ketones using a KI/ tert -butyl hydroperoxide catalytic system. The reaction takes place in water, a green solvent, and does not require a metal catalyst; it also gives good yields of the products. The method offers numerous noteworthy characteristics, including mild reaction conditions, the absence of a base, broad functional-group compatibility, and excellent reaction yields. Moreover, it avoids the use of costly and air-sensitive chemicals, and can be conducted under ambient reaction conditions. [ABSTRACT FROM AUTHOR]

The imidazoheterocycles (fused imidazoles), widely distributed in nature and pharmaceuticals, find many applications in drug discovery, metal sensing and C–H activations, OLEDs, etc. Thus, developing new novel methods for their synthesis has been an active area of research and hence received a great deal attention from synthetic chemists. Likewise, the multicomponent reactions (MCRs) are a hot topic in synthetic research. Herein, we present this review article that covers the multicomponent synthesis of C-3 functionalized imidazoheterocycles from the one-pot reaction of aryl glyoxal, α-aminoazaarene and cyclic 1,3-dicarbonyls and the notable achievements in the area since 2014. Also, this review highlights the substrate-dependent unusual reactions and the potential future perspective in the area for further advancement. The aryl glyoxal-based MCR provides diverse array of highly functionalized imidazoheterocycles from the one-pot MCR of α-aminoazaarene, aryl glyoxal and cyclic 1,3-dicarbonyl through Knoevenagel condensation, Michael addition, intramolecular cyclization and dehydration sequences. [ABSTRACT FROM AUTHOR]

Bis‐heterocycles were synthesized via a consecutive one‐pot process by a Groebke‐Blackburn‐Bienaymé reaction (GBB‐3CR) followed by Copper‐catalyzed Alkyne‐Azide Cycloaddition (CuAAC) assisted by alternative sustainable energies (ASE) such as ultrasonic and mechanical. These efficient and convergent strategies allowed the in situ generation of complex azides functionalized with imidazo[1,2‐a]pyridines (IMPs), which was used as a synthetic platform. The target molecules contain two privileged scaffolds in medicinal chemistry: IMPs and the heterocyclic bioisostere of trans‐amide bond, the 1,4‐disubstituted 1H‐1,2,3‐triazoles (1,4‐DS‐1,2,3‐Ts). [ABSTRACT FROM AUTHOR]

We report a novel, metal‐free procedure for the direct aminophosphonation of imidazo[1,2‐a]pyridines in green solvents under open air conditions. This method is characterized by its mild and sustainable conditions, ease of operation, scalability, and excellent functional group compatibility. The synthesized compounds exhibit promising photophysical properties, including significant Stokes shifts and quantum yields, making them potential candidates for innovative fluorescent probes. [ABSTRACT FROM AUTHOR]

We developed and evaluated several new fused imidazo[1,2‐d][1,2,4]thiadiazolo[1,2,3]triazoles to see how they perform against bacteria and biofilms. Some compounds showed acceptable activity compared to the primary standard, Dicloxacillin. Some of the compounds demonstrated significant antibacterial activity against S. aureus, with MIC values ranging from 1.56–12.5 μg/mL. We also found anti‐biofilm properties in the potent compounds. The results showed that derivatives 3‐(4‐fluorophenyl)imidazo[1,2‐d] [1,2,3] triazolo[1,5‐b][1,2,4]thiadiazole 8,8‐dioxide and 3‐(3,5‐difluorophenyl)imidazo[1,2‐d][1,2,3]triazolo[1,5‐b][1,2,4] thiadiazole 8,8‐dioxide were strong antibacterial agents and effective MSSA and MRSA biofilm growth inhibitors. We conducted in silico studies to assess the molecular interactions of more potent compounds with TLR4 proteins (PDB: 3FXI, 3VQ1, 3RG1). Our findings revealed that 3‐(4‐chloro‐3,5‐dimethoxyphenyl)imidazo[1,2‐d][1,2,3]triazolo[1,5‐b] [1,2,4]thiadiazole 8,8‐dioxide, 3‐(3,5‐dichlorophenyl)imidazo[1,2‐d] [1,2,3]triazolo[1,5‐b][1,2,4] thiadiazole 8,8‐dioxide, and 3‐(4‐(trifluoromethyl)phenyl)imidazo[1,2‐d][1,2,3]triazolo[1,5‐b][1,2,4] thiadiazole 8,8‐dioxide exhibited more binding interactions than dicloxacillin. ADME of more potent compounds examined in this study and compounds could potentially inhibit the cytochrome P450 CYP2C19 isoform. [ABSTRACT FROM AUTHOR]

DDR1 and DDR2 are nonintegrin collagen receptors in the receptor tyrosine kinase family. Both DDRs bind to various collagen types and perform crucial functions in embryo development. DDRs are different from other receptor tyrosine kinases due to their interaction with extracellular matrix components and unusual activation kinetics. DDR regulates cell migration, survival, proliferation, differentiation, and extracellular matrix remodeling. Dysregulated DDR function is linked to the advancement of several human illnesses, including fibrosis, arthritis, neurodegenerative diseases, and cancer. DDRs play a vital role in disease progression and development. Therefore, the use of DDR inhibitors represents a promising therapeutic strategy, particularly for disorders with limited therapy alternatives. In recent years, DDRs have been regarded as attractive targets for drug development, as evidenced by a significant rise in research in this field. The current review illustrates about recent advancement of small molecules, their designing strategies and structure‐activity relationship. The DDR inhibitors can contain various core structures such as pyrimidine, phthalazine, pyrazole, pyrazine, imidazo[1,2‐a]sspyrazine, quinazoline, and thieno[3,2‐b]pyridin‐7‐yl derivatives. Furthermore, based on the constructive analysis of the published derivatives, we found that the majority of the powerful compounds have a similar scaffold (amide linker, hydrophobic tail, hinge binder with or without spacer). Among the different literature, the most potent compounds 4 (imidazo[1,2‐a]pyrazine), 5 (pyridine), 19 (pyridine), and 24 (quinazoline) displayed potent activity against DDR1 with IC50 values ranging from 2.26 – 4.67 nM, while DDR2 IC50 values ranging from 3.2 – 7.29 nM. This approach will help medicinal chemists to refine and develop novel small molecules targeting DDR1 and DDR2. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A novel and eco‐friendly electrochemical activation of trifluoromethyl thianthrenium triflate (TT–CF3+OTf−) for trifluoromethylation of imidazole‐fused heteroaromatic compounds was established. This method involves the direct electrolysis of TT–CF3+OTf− without the requirement of external oxidants or catalysts, aligning with the principles of green chemistry. A wide range of imidazole‐fused heteroaromatic compounds including imidazo[1,2‐a]pyridines and benzo[d]imidazo[2,1‐b]thiazoles have been successfully trifluoromethylated using this technique, exhibiting excellent compatibility with various functional groups and a broad substrate scope. Moreover, the method's applicability for one‐pot sequential reactions enables the reduction of waste and resource consumption by eliminating the need for intermediate purification steps. [ABSTRACT FROM AUTHOR]

As an important class of nitrogen-containing fused heterocyclic compounds, imidazo[1,2-a]pyridines often exhibit significant biological activities, such as analgesic, anticancer, antiosteoporosis, anxiolytic, etc. Using Y(OTf)3 as a Lewis acid catalyst, a simple and efficient method has been developed for the synthesis of C3-alkylated imidazo[1,2-a]pyridines through the three-component aza-Friedel–Crafts reaction of imidazo[1,2-a]pyridines, aldehydes, and amines in the normal air atmosphere without the protection of inert gas and special requirements for anhydrous and anaerobic conditions. A series of imidazo[1,2-a]pyridine derivatives were obtained with moderate to good yields, and their structures were confirmed by 1H NMR, 13C NMR, and HRMS. Furthermore, this conversion has the advantages of simple operation, excellent functional group tolerance, high atomic economy, broad substrate scope, and can achieve gram-level reactions. Notably, this methodology may be conveniently applied to the further design and rapid synthesis of potential biologically active imidazo[1,2-a]pyridines with multifunctional groups. [ABSTRACT FROM AUTHOR]

Diaryl sulfides are known as valuable intermediates in the production of various useful compounds, including antibacterial, antifungal, anti-ulcer and anti-hypertensive agents. In this paper, we developed a new and ecofriendly nanomagnetic catalyst for the synthesis of diaryl sulfides containing imidazo[1,2-a]pyridine, benzoazole, pyrimidine and oxadiazole scaffolds through C–H bond sulfenylation of imidazopyridines. Fe3O4@AMBA–CuI nanocatalyst was successfully constructed through the immobilization of CuI on the surface of magnetic Fe3O4 nanoparticles modified with 3-amino-4-mercaptobenzoic acid (AMBA). FT-IR spectroscopy, SEM, EDX, TEM, XRD, VSM, EDX elemental mapping and ICP-OES techniques were applied to characterize the structure of the as-fabricated Fe3O4@AMBA–CuI nanocatalyst. Recycling of the Fe3O4@AMBA–CuI nanocatalyst was performed up to eight times without significant loss in activity; VSM and ICP-OES techniques confirmed that the stability and high magnetic nature of recovered catalyst. [ABSTRACT FROM AUTHOR]

A new and efficient strategy for the stereoselective synthesis of tetrahydropyridino- and deazepanopyrrolo[1,2- c ]imidazolidines has been developed. Annulation of acylethynylpyrroles with six- and seven-membered cyclic imines (MeCN/THF, 20–25 °C, 24–72 h) leads to tetrahydropyrrolo[1′,2′:3,4]imidazo[1,2- a ]pyridines and hexahydropyrrolo[1′,2′:3,4]imidazo[1,2- a ]azepines with (E)-acylethenyl moiety in 28–96% yields. [ABSTRACT FROM AUTHOR]

An additive‐free, mild, and regioselective C(1)−H nitration of imidazo[1,5‐a]pyridine derivatives was developed. This protocol features the use of easily handled, commercially available, and nontoxic Fe(NO3)3 ⋅ 9H2O both as a nitration source and as a promoter, exhibits good functional group compatibility, and generates the desired nitrated products in acceptable to excellent yields. Mechanistic studies proposed that the nitration reaction may involve a radical C−H functionalization process. [ABSTRACT FROM AUTHOR]

Aqueous zinc‐based energy storage devices have competitive advantages such as high power density, good safety, and wide source. However, because of the direct touch among zinc anode and aqueous electrolyte, dendrite growth and electrode side reactions are easy to occur in the plating and striping process, which seriously hinders the further development of aqueous zinc‐based energy storage devices. Therefore, it is urgent to solve the above problems to expand the existing energy storage devices. In this work, by adding an imidazo[1,2‐b]pyridazine (IP) electrolyte additive, the dendrites' growth and corrosion on the zinc anode surface could be effectively inhibited by the shielding‐anchoring double effects, which are verified by the comprehensive in situ and ex situ characterization techniques as well as the theoretical calculation support. Accordingly, the IP‐based electrolyte encourages extremely high stable zinc anode (cycling 2200 h at 1 mA cm−2) with high average Coulombic efficiency (98.72%). Moreover, the IP‐based Zn‐V2O5 full battery also exhibits excellent reversible capacity, reaching 160.8 mAh g−1 after 400 cycles at 2 A g−1. Through a straightforward alteration to the Zn anode surface, this study considerably enhances the use of highly stable and secure aqueous zinc‐ion batteries. [ABSTRACT FROM AUTHOR]

A great deal of attention has been received on developing N‐heterocyclic compounds due to their ambitious biological activities. Many of them are essential footstep to the development and discovery of new drugs. Imidazole/benzimidazole and quinazoline are essential pharmacologically active N‐heterocycles, and one of the molecular framework built up from their combination, imidazo/benzimidazo[1,2‐c]quinazoline, is of great attention in terms of synthesis, reactions, and medicinal applications. The positional variation of hetero N‐atoms and the functional groups acting as substituents in the main scaffold have a direct impact on the properties of imidazo/benzimidazo[1,2‐c]quinazolines. In addition to its physiological activities, this moiety is useful for electrical conductivity, molecules/ions sensing, coordination complex and coordination polymer (CP) formation, and their diverse applications. The major objective of this review is to highlight various synthetic approaches for imidazo/benzimidazo[1,2‐c]quinazolines motif since 2000. Toxicant‐free reaction conditions and the use of an extensive range of inexpensive substrates are two of the main practical benefits of the protocol in accomplishing the sustainable development goals. [ABSTRACT FROM AUTHOR]

Hydrocarboxylation of methyl 2‐octynoate, a chemical commercially available at a low cost, with N‐protected amino acids was developed with a gold‐zinc cooperative catalyst constructed with a 5‐[(2,2′‐bipyridin)‐5‐yl]imidazo[1,5‐a]pyridin‐3‐ylidene to prepare α‐methoxycarbonyl enol esters as acylating reagents. The α‐methoxycarbonyl enol esters were isolable through silica‐gel column chromatography and storable without precautions regarding moisture. Acylation of free amines with the α‐methoxycarbonyl enol esters proceeded without epimerization of the stereogenic center derived from the enol esters, affording analytically pure dipeptide compounds through filtration and hexane‐washing. [ABSTRACT FROM AUTHOR]

This study presents the synthesis of a novel series of imine derivatives derived from imidazo[1,2‐a]pyridine as potential therapeutic agents. The imines were obtained by condensing 2‐(4‐bromophenyl)‐6‐chloroimidazo[1,2‐a]pyridine‐3‐carbaldehyde with primary amines, leading to high‐purity products that were characterized using various spectroscopic techniques. The compounds demonstrated promising in vitro antimicrobial activity against various bacteria, including Staphylococcus aureus and Escherichia coli, as well as fungi, such as Candida albicans, Saccharomyces cerevisiae, and Aspergillus brasiliensis. Furthermore, the antioxidant properties of the imine derivatives were evaluated using DPPH and ABTS techniques, and the IC50 values measured revealed their ability to scavenge free radicals. Overall, this study provides a valuable contribution to the field of pharmacology by synthesizing a new series of imine derivatives with significant potential as new therapeutic agents, exhibiting both antimicrobial and antioxidant properties. [ABSTRACT FROM AUTHOR]

This article explores the potential of imidazo[1,2-a]pyridine-based donor-acceptor chromophores for the development of novel fluorophores and donor-acceptor chromophores. The authors conducted density functional theory calculations and proposed a modular synthesis approach to access the desired structures. The results show promising potential for the development of thermally activated delayed fluorescence emitters. The article also discusses the synthesis and characterization of a series of donor-acceptor chromophores with a 3-aminoimidazo[1,2-a]pyridine donor motif, highlighting the need for further adjustments and optimizations to improve their optoelectronic properties. The modular synthesis approach used in this study provides a versatile platform for the development of new fluorescent emitters. [Extracted from the article]

This article discusses the metal-free synthesis of trifluoromethyl carbinol-containing imidazo[1,2-a]pyridines through dehydrative coupling. Trifluoromethyl-containing compounds are important in various fields due to their biological activity and stability. Imidazo[1,2-a]pyridines are commonly found in pharmaceuticals, and the construction of CF3-containing imidazo[1,2-a]pyridines is valuable for drug discovery. The use of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as a medium for organic synthesis has been explored, and it has been found to promote the hydroxy-trifluoromethylation of imidazo[1,2-a]pyridines with trifluoroacetaldehyde. The optimized reaction conditions using HFIP as a solvent resulted in good yields of the desired products. The substrate scope of this process was also investigated, demonstrating its generality and practicality. This article describes a novel approach for the synthesis of trifluoromethyl carbinol-containing imidazo[1,2-a]pyridines using imidazo[1,2-a]pyridines and trifluoroacetaldehyde via a dehydrative cross-coupling process. The reaction was promoted by HFIP and exhibited wide substrate generality, excellent functional group tolerance, and mild reaction conditions. [Extracted from the article]

Imidazopyridine and pyranopyrazole derivatives include a very important class of heterocyclic compounds that have many biological properties and have been observed in the structure of many drugs and bioactive molecules. In this research project, we first successfully made copper catalyst immobilized on magnetic iron nanoparticles modified with dopamine and 1H-benzo[d]imidazole-2-carboxylic acid (as magnetic ligand) and confirmed its structure with a series of spectroscopic techniques; then in the next step, the catalytic activity of this nanocomposite [Fe3O4@Dop/Amide-BenzImid-CuBr2] was evaluated the nanocomposite in the multicomponent synthesis of imidazo[1,2-a]pyridine and pyranopyrazole derivatives. The results clearly showed that this magnetic nanocatalyst in water solvent under reflux conditions is a very efficient catalytic system for the synthesis of imidazo[1,2-a]pyridines and pyranopyrazoles because all the products were synthesized with high to excellent yields in a suitable period of time. Also, the recovery tests confirmed that the Fe3O4@Dop/Amide-BenzImid-CuBr2 catalyst can be reused up to 8 times without significantly reducing its catalytic efficiency. VSM and ICP-OES analyses confirmed the stability, magnetism and high efficiency of the catalyst after repeated use of the catalyst. [ABSTRACT FROM AUTHOR]

Pharmacotherapy protocols used in cancer treatment are far from curative for many patients due to reasons such as drug-related toxicity and decreased effectiveness of the drug. Multidrug resistance is a defense mechanism developed by the cancer cell against different drug groups or drug combinations. One of the most important reasons is the increase in the efficiency or number of ABC transporters that ensure drug removal from the cell. Imidazopyridines, which are incorporated into the structure of many biomolecules, have been produced under laboratory conditions for many years. Imidazopyridines are effective anticancer agents that can kill cancer cells in various ways. In this review, we presented a detailed summary of studies in which imidazopyridines were used to overcome multidrug resistance by targeting ABC transporters in cancer cells. For this purpose, we collectively evaluated the synthesis strategies and laboratory results of the agents synthesized and used as drugs and the compounds whose clinical trials have not yet started. The introduction of several imidazopyridine derivatives as prescription drugs reflects the potential of these molecules. We think that agents that can provide targeted therapy will be used more frequently in the clinic and will improve treatment success. [ABSTRACT FROM AUTHOR]

Recently, the development of supported ionic liquid on magnetic nanoparticles (MNP) and multicomponent reactions in industry and academia has been a matter of intense study. In this new and environmentally benign synthetic methodology, a dihydroxyl functionalized basic ionic liquid precursor was immobilized onto the magnetic silica nanoparticles via covalent bonding to prepare a novel powerful basic catalyst (DHBIL@Si-MNPs). The synthesized catalyst was characterized extensively by various techniques. Also, the alkalinity of the DHBIL@Si-MNPs catalyst (pKb value) was obtained at 9.23. The catalytic activity of the prepared catalyst was investigated in a one-pot and three-component reaction between pyridine, phenacyl bromide, and thiocyanate to afford corresponding substituted imidazo [1,2-a] Pyridine derivatives under solvent-free conditions. Different spectroscopic methods were used to establish the structures of target compounds. The imidazopyridines were generated in excellent yields (80–98%) under the optimum conditions utilizing 10% by weight of DHBIL@Si-MNPs to pyridine, a molar ratio of 1.2: 1.2: 1 mmol (mmol), and a temperature of 100 °C. The present developed synthetic protocol permits the production of interesting medicinal compounds with high purity and different functional group tolerating abilities. Also, the other significant advantages of this protocol are highlighted by less reaction time, cleaner reaction profiles, avoidance of toxic catalysts, simplicity of the process, benign reaction conditions, use of available raw materials, and easy separation of products. The catalyst could be easily recycled from the reaction mixture using an external magnet thanks to its superparamagnetic and reused several times without any appreciable decrease in its reactivity and product yield. [ABSTRACT FROM AUTHOR]

Chronic neuroinflammation is crucial in many neurodegenerative diseases, including AD. Neuroinflammation activates microglia, the CNS's central effector cells, and immune cells. Toxins and neuroinflammatory reactions can kill or damage neurons, activating microglial cells. Inflammatory mediators from activated microglia can kill neurons like cytokines, chemokines, reactive oxygen species, and reactive nitrogen species. Imidazo[1,2‐α]azines with different acid groups in position two of the heterocycle system were synthesized and tested as anti‐inflammatory and cell immunomodulators. We measured the ability of human neuroblastoma (SHSY‐5Y) and microglial (HMC3) cell lines to decrease PGE2 production under pro‐inflammatory conditions. All derivatives reduced PGE2 production. Inhibitory profiles indicate that compounds 8a and 8b are more effective and potent than 9a and 9b, indicating a steric effect of carboxyphenyl on imidazo[1,2‐α]azines, reducing their potency. However, imidazo[1,2α]pyrimidines (8b and 9b) with nitrogen at position 8 were less effective than those observed by other groups (8a, 9a, and 10a). imidazo[1,2‐α]pyrimidines are more polar due to nitrogen at position 8. The synthetically derivative imidazo[1,2‐α]pyridines decreased PGE2 formation in vitro on neural cells, microglia (HMC3), and neuroblastoma (SH‐SY5Y) cells, proving that they are more effective than imidazo[1,2‐α]pyrimidines. Two product esters selectively reduced HMC3 microglial cell PGE2 production. This finding may help develop neurodegenerative disease anti‐inflammatories. [ABSTRACT FROM AUTHOR]

A new efficient method was developed for the synthesis of 2-(imidazo[1,2-a]pyridin-2-yl)benzimidazoles based on the Mamedov rearrangement. The key step of the synthesis involves the acid-catalyzed rearrangement of spiroquinoxalinone derivatives as intramolecular cyclization products of 2-amino-1-[(quinoxalin-2(1H)-on-3-yl]methyl)pyridinium salts, which are generated by the modified Chichibabin reaction. [ABSTRACT FROM AUTHOR]

Novel imidazopyridines hydrazine conjugates were designed and synthesized for their anti‐tubercular (anti‐TB) activity. A cytotoxicity assay was conducted with Vero cells to determine the safety profile of the most effective compounds. It was found that compound (IA3) (MIC=0.78 μM) and (IA8) (MIC=1.12 μM) were nearly 3.7 and 2.5 times more active than pyrazinamide. Based on Density functional theory (DFT), these molecules exhibited better charge transfer between molecular orbital's, which made them suitable for biological applications. Molecular docking on Mycobacterium tuberculosis InhA bound to NITD‐916 (PDB: 4R9S) revealed that compounds possessed greater binding affinity towards proteins. In addition, the most active anti‐TB compounds (IA3) and (IA8) exhibited high levels of interaction with the target protein and exceptional safety profile, suggesting they may prove to be effective leads for new drugs. [ABSTRACT FROM AUTHOR]

This study focuses on the cytotoxic effect properties of 4‐aryl‐functionalized benzo[d,e]benzo[4,5]imidazo[2,1‐a]isoquinolin‐7‐one (4‐X−Ar−BBI). The electron‐withdrawing and electron‐donating substituents located at the para position of the phenyl ring attached to the heterocyclic structure have altered the pi electron density within the structure. This change in electron density has influenced the intercalation ability of the heterocyclic structure and has impacted the intensity of its interaction with DNA. The 4‐aryl‐benzo[d,e]benzo[4,5]imidazo[2,1‐a]isoquinolin‐7‐one derivatives (4‐X−Ar−BBI) were prepared via the Suzuki–Miyaura cross‐coupling reaction. The optimum reaction conditions were determined to be 70 °C for 5 hours using catalyst 1 and K2CO3, resulting in a yield of 96 % of 4‐H−Ar−BBI. Characterization of all compounds (4‐X−Ar−BBI) was performed using Fourier Transform Infrared spectroscopy, mass spectrometry, and 1H‐ and 19F‐NMR spectroscopies. The cytotoxic activities of the compounds (4‐X−Ar−BBI) were investigated against cancer cell lines, specifically HeLa (human cervix adenocarcinoma epithelial), PC3 (human prostate), and MCF‐7 (human breast). The stability of 4‐CN−Ar−BBI and the binding modes between 4‐CN−Ar−BBI and DNA were investigated via 1H‐NMR spectroscopy and UV‐Vis spectroscopy, respectively. 4‐CH3−3‐NO2−Ar−BBI exhibited the most potent cytotoxic activity against MCF‐7, and 4‐F−Ar−BBI showed the highest activity against HeLa, with IC50 values of 3.675 and 7.370 μM, respectively. [ABSTRACT FROM AUTHOR]

A series of fifteen novel amide derivatives based on imidazo[1,2‐b]pyridazine scaffold were synthesized by taking imidazo[1,2‐b]pyridazine‐3‐carboxylic acid intermediates with respective substituted amines to yield good to excellent. The molecular structures of the newly synthesized compounds were elucidated using spectroscopic techniques (1H NMR, 13C NMR, and LCMS) and supported by single‐crystal X‐ray diffraction (SXRD) for the two compounds, 9 and 18. These compounds were evaluated in vitro for antimicrobial activity against two Gram‐positive bacteria (S. aureus and B. subtilis) and two Gram‐negative bacteria (E. coli and P. aeruginosa). Interestingly, compounds 10 and 16, displayed comparable antibacterial activity to the positive control (Tetracycline: 6.25 μg/mL) against Gram‐negative bacteria, particularly Pseudomonas aeruginosa, with a minimum inhibitory concentration (MIC) of 6.25 μg/mL. Compound 17 exhibited moderate antibacterial activity with an MIC of 10 μg/mL against the Gram‐positive bacterium Bacillus subtilis, whereas the positive control demonstrated an MIC of 6.25 μg/mL. These antibacterial activities were found to have a good correlation with Insilco computational molecular docking experiments using the receptor UDP‐N‐acetylglucosamine‐enolpyruvate reductase, Mtb MurB. [ABSTRACT FROM AUTHOR]

We report here a catalyst‐free, (sp2)C−H imination reaction of in‐situ formed imidazo[1,2‐a]pyridines and α‐iminoketones. This one‐pot, multicomponent, and atom economic reaction is performed at moderate to room temperature without the need for any catalyst and inert conditions. The reaction showed good substrate tolerance with appreciable yields. Gram‐scale synthesis and post‐synthetic modifications to obtain 1,2‐diketones are also described. [ABSTRACT FROM AUTHOR]

Herein, we report a solvent-free and sustainable methodology for the electrophilic C–H thiocyanation of indoles and imidazo[1,2-a]pyridines in a mixer-mill. A combination of commercially available and cheaper precursors N-chlorosuccinimide and NaSCN was used under milling conditions for the in situ generation of N-thiocyanatosuccinimide (NTS) which facilitates the C-3 selective thiocyanation reaction on indoles and imidazo[1,2-a]pyridines. A series of thiocyanated products containing electron-rich and electron-deficient rings were synthesized in silica gel as the solid reaction media and good to excellent yields were obtained. The scalability of the reaction was validated with selected substrates at the gram scale. Moreover, we explored mechanochemical tandem C–C and C–S bond formation reactions by double C–H activation, leading to easy access to C-2 aryl and C-3 thiocyanato compounds from unsubstituted indoles. In addition, mechanochemical conversion of the –SCN precursors into –SCF3 and 5-substituted sulfenyl tetrazole was also demonstrated in the current methodology. [ABSTRACT FROM AUTHOR]

An efficient electrochemical dual C(sp3)–H amination was developed under metal-free and chemical oxidant-free conditions. A series of imidazo[1,5-a]quinazolin-5(4H)-ones and 5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carbonitriles can be obtained in high yields and the product distribution can be modulated by virtue of this method. The reaction mechanism was investigated and the corresponding intermediates were studied. The reaction features a broad substrate scope, regulation of the product distribution, mild conditions and scalable preparation. [ABSTRACT FROM AUTHOR]

Nonenzymatic browning poses a severe problem to the dairy industry, causing economic losses. In this work, an untargeted metabolomics approach based on ultra‐high‐performance liquid chromatography coupled with Orbitrap mass spectrometry was used to investigate the discoloration found on the inner parts of nonprotected designation of origin Italian hard cheese. Alkyl‐pyrazines, imidazo‐quinoxalines and β‐carbolines were the best markers, suggesting the involvement of microbial methylglyoxal in modulating the browning defect. A better understanding of the microbial composition of natural whey starter could be of interest in future studies to better elucidate the biochemical mechanisms involved and to help generate discriminant metabolites. [ABSTRACT FROM AUTHOR]

Here we report the synthesis and anticancer activities of fourteen novel imidazo[1,2-a]pyridine derivatives (6a-6n) containing S-alkyl/aryl moiety. The target compounds were obtained via a six-step synthetic route. 1-(4-Aminophenyl)ethan-1-one was the starting material. In the last step, 2-chloro-N-[4-(imidazo[1,2-a]pyridin-2-yl)phenyl]acetamide (5) was allowed to react with various aliphatic/aromatic thiol derivatives, affording the final compounds 6a-6n. The cytotoxicity of the compounds was evaluated against A549 (human non-small cell lung cancer), C6 (rat glioma), MCF-7 (human breast carcinoma) and HepG2 (human liver carcinoma) tumor cells and NIH/3T3 (mouse embryonic fibroblast cells) healthy cells. First step MTT assay reported that compounds 6a, 6d, 6e and 6i exhibited antiproliferative activity against all tested tumor lines. Second step BrdU cell proliferation assay and flow cytometric analysis revealed that compounds 6d and 6i inhibited DNA synthesis on HepG2 cell line time-dependently by apoptotic pathway. Molecular docking study of compounds 6d and 6i with caspase-3 and caspase-9 revealed their binding interactions with the enzyme's active site, confirming the experimental findings. [ABSTRACT FROM AUTHOR]

Several heterocyclic compounds bearing an imidazo(1,2a)pyridine moiety have been synthesized in this work, including triazole, thiazol, and thiazolone. This was done by condensation of 2-aminopyridine with 2-aminopyridine with 4- bromophencyl bromide or 4-phenylphencyl bromide to produce 2-substituted phenyl imidazo(1,2a)pyridine compounds 1 and 2. The Vilsmeier-Haak reaction was used to create the aldehyde group at position 3 of the 2-substituted phenyl imidazo(1,2a)pyridine ring (3 and 4). The reaction of compounds 3 and 4 with thiosemicarbazide afforded thiosemicarbazone derivatives 5 and 6 in 66 and 70% yields, respectively. These derivatives (5 and 6) were then subjected to three different cyclization reactions to obtain 1,3-thiazolone (7 and 8), 1,2,4-triazole (9 and 10), and 1,3-thiazole (11 and 12) derivatives. The FT-IR spectroscopy was used to confirm the structure of these derivatives, and the 1H NMR spectroscopy was used for some of them. A few of the produced compounds were examined for antimicrobial and antioxidant activities [ABSTRACT FROM AUTHOR]

The advancement of sustainable chemistry and changes in the economy are strongly intertwined. Reaction time, cost savings, moderate temperatures, and generation of the fewest byproducts are frequently achieved by using catalytic processes. Herein, we report the C−H olefination of imidazo[1,2a] pyridine carboxamides with various acrylates in the presence of Pd (OAc)2 with O2 as the oxidant in aqueous ethanol rather than using non‐ecofriendly solvents. The C−H activation features most user‐friendly reaction conditions, excellent yield as well as plenty substrate scope and applicable for C−H deuteriation of the corresponding heteroarenes with D2O. Experimental mechanistic studies indicate that C−H activation step succeeded after formation of tetra coordinated square planer Pd‐substrate adduct. [ABSTRACT FROM AUTHOR]

Cancer is a serious threat to human life and social development and the use of scientific methods for cancer prevention and control is necessary. In this study, HQSAR, CoMFA, CoMSIA and TopomerCoMFA methods are used to establish models of 65 imidazo[4,5-b]pyridine derivatives to explore the quantitative structure-activity relationship between their anticancer activities and molecular conformations. The results show that the cross-validation coefficients q2 of HQSAR, CoMFA, CoMSIA and TopomerCoMFA are 0.892, 0.866, 0.877 and 0.905, respectively. The non-cross-validation coefficients r2 are 0.948, 0.983, 0.995 and 0.971, respectively. The externally validated complex correlation coefficients r2pred of external validation are 0.814, 0.829, 0.758 and 0.855, respectively. The PLS analysis verifies that the QSAR models have the highest prediction ability and stability. Based on these statistics, virtual screening based on R group is performed using the ZINC database by the Topomer search technology. Finally, 10 new compounds with higher activity are designed with the screened new fragments. In order to explore the binding modes and targets between ligands and protein receptors, these newly designed compounds are conjugated with macromolecular protein (PDB ID: 1MQ4) by molecular docking technology. Furthermore, to study the nature of the newly designed compound in dynamic states and the stability of the protein-ligand complex, molecular dynamics simulation is carried out for N3, N4, N5 and N7 docked with 1MQ4 protease structure for 50 ns. A free energy landscape is computed to search for the most stable conformation. These results prove the efficient and stability of the newly designed compounds. Finally, ADMET is used to predict the pharmacology and toxicity of the 10 designed drug molecules. [ABSTRACT FROM AUTHOR]

A series of 8‐(piperazin‐1‐yl) imidazo [1,2‐a] pyrazine derivatives were designed and synthesized as acetylcholinesterase inhibitors (AChEIs) and antioxidants for the treatment of Alzheimer's disease (AD). Moreover, the biological evaluation results demonstrated that these synthesized compounds exhibited moderate inhibitory activities toward acetylcholinesterase (AChE) and radical scavenging activities. Among them, the compound with the strongest inhibitory activity against AChE had an IC50 value of 0.55 μM, which was higher than that of galantamine as the reference compound (IC50 value=5.01 μM). The compound with the strongest antioxidant activity had an IC50 value of 57.94 μM, which was lower than that of the ascorbic acid (IC50 value=25.70 μM) as the control drug. Furthermore, the results of molecular docking studies indicated that the compound could simultaneously bind to both catalytic active site (CAS) and peripheral anionic site (PAS) of AChE, which was consistent with the mixed inhibition pattern shown by enzyme kinetic studies. The interaction's stability was also assessed using a conventional atomistic 100 ns dynamics simulation study, which revealed the conformational stability of representative compound in the cavity of the AChE. In addition, the molecular properties of all compounds were predicted online through the SwissADME, and most compounds matched the properties of most orally administered drugs. Based on the biological activity and molecular properties, 8‐(piperazin‐1‐yl) imidazo[1,2‐a] pyrazine derivatives as AChEI were valuable for further development. [ABSTRACT FROM AUTHOR]

Recently, achieving selective cancer therapy with trifling side effects has been a great challenge in the eradication of cancer. Thus, to amplify the cytoselective approach of complexes, herein, we developed a series of Re(I)[2-aryl-1H-imidazo[4,5-f][1,10]phenanthroline] tricarbonyl chloride complexes and screened their potency against HeLa and MCF-7 cell lines together with the evaluation of their toxicity towards a normal kidney cell line (HEK-293). On meticulous investigation, complex [ReI(CO)3Cl(K2-N,N-(2c))] (3c) was found to be the most potent anticancer entity among other complexes. Complex 3c also showed competency to induce apoptosis in MCF-7 cells through G2/M phase cell-cycle arrest in association with the generation of ample reactive oxygen species (ROS), eventually leading to DNA intercalation and internucleosomal cleavage. The order of the cytotoxicity of these complexes depended on their lipophilic character and the electron-withdrawing halogen substitution at the para-position of the phenyl ring in the imidazophenanthroline ligand. [ABSTRACT FROM AUTHOR]

The effectiveness of synthesized antipyrinyl‐imidazotriazole and its derivatives as inhibitors for the corrosion of copper alloy in 0.5 M H2SO4 solution was tested using weight loss, electrochemical impedance spectroscopy (EIS) and potentiodyanmic polarization techniques. The generated results confirmed that the tested compounds have strong inhibition efficiencies for the protection of the corrosion of copper alloy in 0.5 M H2SO4. Maximum inhibition efficiencies (IEs) evaluated from electrochemical measurements at inhibitor's concentrations of 0.040 g/L were 85% (5‐(4‐Antipyrinyl)‐3H‐imidazo[1,2‐b][1,2,4]triazole), 60% (6‐Antipyrinyl‐imidazo[2,1‐b]thiazole) and 72% (2‐Antipyrinyl‐7‐ethoxy‐imidazo[2,1‐b]benzothiazole). It was observed that the inhibition efficiency was strongly influenced by the flow rate of the solution and was reduced to 79 (5‐(4‐Antipyrinyl)‐3H‐imidazo[1,2‐b][1,2,4]triazole), 60% (6‐Antipyrinyl‐imidazo[2,1‐b]thiazole), and 44% (2‐Antipyrinyl‐7‐ethoxy‐imidazo[2,1‐b]benzothiazole) at an agitation speed of 400 rpm. EI from weight loss was comparable with those from PDP of mixed‐type inhibition style and EIS of diffusion model. The low inhibition efficiency for 6‐Antipyrinyl‐imidazo[2,1‐b]thiazole was significantly enhanced from 60% to 90% through a synergistic effect of 0.0001 M KI. The Temkin and Frumkin isotherms indicate the physical adsorption of inhibitors on copper surface. Condensed Fukui function calculations reveal a common center for electrophilic attacks in the three molecules: the nitrogen in the bridged pyrrole rings (labeled as N11). [ABSTRACT FROM AUTHOR]

In this contribution, new derivatives of bicyclic fused rings with a bridgehead nitrogen atom were synthesized from the imidazo[1,2-a]pyridine derivatives C1 by reacting two moles of 2-aminopyridine and 4-aminoacetophenone with iodine in a one-pot reaction. This compound (C1) was then condensed with 2- nitrobenzaldehyde and 2,4-dichlorobenzaldehyde to form new derivatives of Schiff bases (C2 and C3). These Schiff bases were then cyclized to synthesize thiazolidin4-one derivatives (C4 and C5), tetrazole derivatives (C6 and C7), and aza-β-lactam derivatives (C8 and C9) through the reactions with thioglycolic acid, sodium azide, and 1-naphthylisocyanate, respectively. FT-IR, 1H NMR, and 13C NMR spectroscopy were used to characterize these new compounds. In the second part of this work, the antioxidants of these compounds were measured, and results ranged from good to medium. [ABSTRACT FROM AUTHOR]

The synthesis of a novel imidazo[4,5-b]pyridine and its partially saturated derivative relied on Michael addition of 1-methyl-1H-imidazol-4-amine to fumaric/maleic or acetylene dicarboxylates, followed by intramolecular cyclization into target compounds. The common transformations of the resulting pyridine carboxylate were performed to obtain a series of building blocks, i.e. carboxylic acids, amides, and amines. The pyridone fragment was transformed into the fused bromopyridine moiety which was used for Buchwald–Hartwig and Suzuki cross-coupling reactions providing a versatile access to an extended scope of imidazopyridines. All synthesized building blocks could be considered as promising purine bioisosteres for the synthetic and medicinal chemistry. [ABSTRACT FROM AUTHOR]

In this work, we report an effective, one‐pot syntheses of benzo[4,5]imidazo[1,2‐a]pyrimidine and pyrano[4,3‐b]pyran derivatives using L‐glutamine functionalized nanoparticles (Fe3O4@SiO2@L‐glutamine NPs) under microwave irradiation. The organo‐nanocatalyst underwent characterization through diverse techniques, including FT‐IR, p‐XRD, SEM, TEM, EDX, XPS, TGA, and VSM. Microwave irradiation and multicomponent reactions synergistically yield excellent product yields (≈80%–95%) in shorter reaction times (≈6–15 min) with a broader substrate scope. The organo‐nanocatalyst displays notable catalytic efficacy, evidenced by high turnover numbers (TON) and turnover frequencies (TOF) across syntheses. This innovative protocol showcases exceptional efficiency, cost‐effectiveness, and environmental friendliness, with advantages like minimal reaction conditions, easy catalytic recovery, recyclability, operational simplicity, and the use of eco‐friendly solvents. [ABSTRACT FROM AUTHOR]

Trifluoromethyl cationic carbyne (CF3C+:) possessing dual carbene‐carbocation behavior emulated as trifluoromethyl metal‐carbynoid (CF3C+=M) has not been explored yet, and its reaction characteristics are unknown. Herein, a novel α‐diazotrifluoroethyl sulfonium salt was prepared and used in Rh‐catalyzed three‐component [2+1+2] cycloadditions for the first time with commercially available N‐fused heteroarenes and nitriles, yielding a series of imidazo[1,5‐a] N‐heterocycles that are of interest in medicinal chemistry, in which the insertion of trifluoromethyl Rh‐carbynoid (CF3C+=Rh) into C=N bonds of N‐fused heteroarenes was involved. This strategy demonstrates synthetic applications in late‐stage modification of pharmaceuticals, construction of CD3‐containing N‐heterocycles, gram‐scale experiments, and synthesis of phosphodiesterase 10A inhibitor analog. These highly valuable and modifiable imidazo[1,5‐a] N‐heterocycles exhibit good antitumor activity in vitro, thus demonstrating their potential applications in medicinal chemistry. [ABSTRACT FROM AUTHOR]

An efficient electrochemical methylthiolation reaction of imidazo[1,2-a]pyridines was achieved. The method used DMSO as both the methylthiolating reagent and solvent and KI as both the hydrogen atom transfer reagent and supporting electrolyte. The reaction was performed under transition metal- and chemical oxidant-free conditions. For various substituted 2-arylimidazo[1,2-a]pyridines, C-3 methylthiolation products were obtained regioselectively with good yields. [ABSTRACT FROM AUTHOR]

This article discusses the synthesis and potential therapeutic applications of chirally enriched 1H-imidazo[1,2-b]pyrazole and 4H-imidazo[1,2-b][1,2,4]triazole-based bioactive glycohybrids. These compounds have shown significant biological and pharmacological properties, including anticancer, antiviral, and antibacterial activities. The researchers successfully synthesized various glycohybrids using different synthetic routes and optimized reaction conditions. The synthesized compounds were tested for their anticancer activity, with some showing moderate growth inhibition in breast cancer cells. In silico docking studies also suggested their potential as new chemical entities in drug discovery. The synthesis and characterization of the compounds were achieved using robust methods, and the compounds were characterized using various spectroscopic techniques. The article provides detailed information on the synthetic strategies and reaction conditions used in the synthesis of these compounds. The authors acknowledge the support of Banaras Hindu University and Jawaharlal Nehru University in conducting this research. [Extracted from the article]

Here, we present the development of a synthesis for imidazo[1,2a] pyridine/thiazole derivatives catalyzed by a heterogeneous basic support, specifically Amberlyst® A‐26(OH) ion exchange resin, in a water medium at 60 °C. In pursuit of a green methodology, we opted for this polyionic exchange resin due to its thermal stability and recyclability. Notably, this protocol eliminates the need for strong bases, organic solvents, and additives. The remarkable aspect of this reaction lies in utilizing water as a green solvent, and the synthesized products are easily purified through a straightforward crystallization method. The NMR (1H and 13C) spectroscopy is employed for the characterization of the synthesized products. Furthermore, we explore the additional functionalization of imidazo[1,2a] pyridine/thiazole derivatives. [ABSTRACT FROM AUTHOR]

Introduction: Imidazo[1,2- a ]pyridine derivatives with diverse pharmacological properties and curcumin, as a potential natural anti-inflammatory compound, are promising compounds for cancer treatment. This study aimed to synthesize a novel imidazo[1,2- a ]pyridine derivative, (MIA), and evaluate its anti-inflammatory activity and effects on nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) pathways, and their target genes, alone and in combination with curcumin, in MDA-MB-231 and SKOV3 cell lines. Methods: We evaluated the interaction between imidazo[1,2- a ]pyridine ligand, curcumin, and NF-κB p50 protein, using molecular docking studies. MTT assay was used to investigate the impacts of compounds on cell viability. To evaluate the NF-κB DNA binding activity and the level of inflammatory cytokines in response to the compounds, ELISA-based methods were performed. In addition, quantitative polymerase chain reaction (qPCR) and western blotting were carried out to analyze the expression of genes and investigate NF-κB and STAT3 signaling pathways. Results: Molecular docking studies showed that MIA docked into the NF-κB p50 subunit, and curcumin augmented its binding. The MTT assay results indicated that MIA and its combination with curcumin reduced cell viability. According to the results of the ELISA-based methods, MIA lowered the levels of inflammatory cytokines and suppressed NF-κB activity. In addition, real-time PCR and Griess test results showed that the expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) genes, and nitrite production were reduced by MIA. Furthermore, the western blotting analysis demonstrated that MIA increased the expression of inhibitory κB (IκBα) and B-cell lymphoma 2 (Bcl-2)-associated X proteins (BAX), and suppressed the STAT3 phosphorylation, and Bcl-2 expression. Our findings revealed that curcumin had a potentiating role and enhanced all the anti-inflammatory effects of MIA. Conclusion: This study indicated that the anti-inflammatory activity of MIA is exerted by suppressing the NF-κB and STAT3 signaling pathways in MDA-MB-231 and SKOV3 cancer cell lines. [ABSTRACT FROM AUTHOR]