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Copyright of Baghdad Science Journal is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The rise of multidrug‐resistant organisms (MDROs) represents a significant challenge to healthcare, underscoring the need for novel antimicrobial agents. Quinazolinone compounds, noted for their diverse biological activities, particularly at the 2nd and 3rd positions, in conjunction with sulphanilamide and isatin derivatives, present a promising avenue for antibacterial development. This study focuses on the synthesis of novel 2,3‐disubstituted quinazolin‐4(3H)‐one derivatives from Schiff base intermediates GA3A and GA3B. The synthesis involved the reaction of 2‐(substituted phenyl)‐4H‐benzo[d][1,3]‐oxazin‐4‐one with sulphanilamide, and the benzoxazinone intermediates were prepared by reacting anthranilic acid with benzoyl chloride. The antibacterial activities of the Schiff base intermediates and the final Mannich base compounds were evaluated against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa at concentrations of 50 µg/mL and 100 µg/mL using the agar well diffusion method, with Norfloxacin (50 µg/mL) as the reference standard. While all tested compounds exhibited lower antibacterial activity compared to the standard, GA4A1 showed enhanced efficacy against E. coli, achieving the highest docking score of 78.0352 against the E. coli protein (PDB ID: 1KZN). Molecular dynamics simulations revealed that the GA4A1‐E. coli complex stabilized after 40,000 ps, with root mean square deviation (RMSD) values ranging from 2.5 Å to 5 Å and low root mean square fluctuation (RMSF) values between 0.05 Å and 0.2 Å, indicating the stability of the complex. These findings underscore GA4A1's potential as a potent antimicrobial agent against E. coli. [ABSTRACT FROM AUTHOR]

The synthesis and characterization of two novel diastereomeric Mannich bases was carried out from the reaction of the cyclic aminal (2R,7R,11S,16S)-1,8,10,17-tetraazapentacyclo[8.8.1.1.8,170.2,70.11,16]icosane 1 and p-cresol 2a and 4-methoxyphenol 2b in a water/dioxane mixture. The title compounds (4a–b) are interesting because bearing two 3-(2-hydroxy-5-substitutedbenzyl)octahydro-1H-benzimidazol-1-yl]methyl} substituents joined to an arenol ring. The formation of these new Mannich bases in the reaction mixture can be explained by aminomethylation of previously reported di-Mannich base 2,2′-((hexahydro-1H-benzo[d]imidazole-1,3(2H)-diyl)bis(methylene))bis(4-substituentphenol) 3a–b. NMR analysis demonstrated that compounds 4a–b were formed as diastereomeric mixtures. Subsequent experiments revealed that at longer reaction times, the percentage yield of these new products increased considerably (yield percentages up to 22–27%), suggesting a nucleophilic competition between the p-substituted phenols and Mannich bases of type 3 for aminal 1. [ABSTRACT FROM AUTHOR]

The reaction between glycine-type aminonaphthol derivatives substituted with 2- or 1-naphthol and indole or 7-azaindole has been tested. Starting from 2-naphthol as a precursor, the reaction led to the formation of ring-closed products, while in the case of a 1-naphthol-type precursor, the desired biaryl ester was isolated. The synthesis of a bifunctional precursor starting from 5-chloro-8-hydroxyquinoline, morpholine, and ethyl glyoxylate via modified Mannich reaction is reported. The formed Mannich base 10 was subjected to give bioconjugates with indole and 7-azaindole. The effect of the aldehyde component and the amine part of the Mannich base on the synthetic pathway was also investigated. In favor of having a preliminary overview of the structure-activity relationships, the derivatives have been tested on cancer and normal cell lines. In the case of bioconjugate 16, as the most powerful scaffold in the series bearing indole and a 5-chloro-8-hydroxyquinoline skeleton, a potent toxic activity against the resistant Colo320 colon adenocarcinoma cell line was observed. Furthermore, this derivative was selective towards cancer cell lines showing no toxicity on non-tumor fibroblast cells. [ABSTRACT FROM AUTHOR]

We report the detailed mechanistic insights of L-proline catalyzed, solvent-controlled, regioselective Mannich reaction. Different solvation models were employed to understand the formation of critical intermediates. The seminal difference in the nature of H-acceptor solvents and H-donor solvents leads to variation in the attachment site on the reactant molecule. Our calculations suggest that the H-acceptor solvent exhibits selective non-covalent interaction with α-hydrogen atoms of the iminium group, facilitating the reactivity at the more hindered site, which results in the formation of a branched isomer. On the other hand, the H-donor solvent preferentially binds to the carboxylate group, thus enabling the reactivity to proceed from the less hindered carbon chain, leading to a linear isomer. The above distinct interactions force a regioselective generation of enamines. Thus, the iminium ion's site-specific solvent interaction has been observed to cause a switch in the regioselectivity. These enamines subsequently react with cyclic ketone to produce Mannich base with excellent enantioselectivity (>99%ee). [ABSTRACT FROM AUTHOR]

Copyright of Iraqi Journal of Chemical & Petroleum Engineering is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The continuous improvement of synthesis methods enables the optimization of the process for developing and obtaining target products of chemical transformation. Derivatives of 1,2,4-triazole-3-thiol present a convenient object for chemical transformation, facilitating the creation of promising biologically active compounds. Combining the structure of this heterocyclic system with pharmacophore fragments of different natures allows for more effective work on the development of molecules with high pharmacological potential. To implement this strategy, 2-,3-,4-fluorophenyl-4-amino-1,2,4-triazol-3-thiones were utilized as starting structures. This molecule possesses three reaction centers, facilitating a wide range of chemical transformations involving these substances. The aim of the work was to create a series of 4-amino-2-((R1,R2-amino)methyl)-5-((2-,3-,4)-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones as a promising source for the preparation of biologically active substances. Materials and methods. The structure of the target compounds has been formed using well-known methods of organic chemistry. The starting materials used were 2-,3-,4-fluorophenyl-4-amino-1,2,4-triazol-3-thiones, which were previously obtained. The first stage of the work involved the temporary protection of the amino group with a tert-butoxycarbonyl group. The second stage of the work involved the realization of Mannich reactions involving primary and secondary amines. The reaction has been carried out with formalin in an alcohol-dioxane medium. The products of the chemical transformation have been recrystallized in methanol. The third stage of the work was based on the removal of Boc-protection, which was realized using hydrochloric acid in a dioxane medium. The structures of all synthesized substances have been determined by 1H NMR spectroscopy and elemental analysis. The individuality of the compounds has been confirmed by high-performance liquid chromatography. Results. The successful study of the mechanisms of Mannich reactions for 4-amino-1,2,4-triazole-3-thione derivatives allowed us to obtain 4-amino-2-((R1,R2-amino)methyl)-5-((2-,3-,4)-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones in quantitative yields. The studies made it possible to establish the favorable effect of protecting the amino group of the 2-,3-,4-fluorophenyl-4-amino-1,2,4-triazole-3-thione of the tert-butyloxycarbonyl group on the course and direction of the reaction. Conclusions. The optimal conditions for the Mannich reactions involving 2-,3-,4-fluorophenyl-4-amino-1,2,4-triazole-3-thione with intermediate Boc-protection of the amino group have been determined, which allowed us to create the theoretical basis for the successful use of Mannich reactions to expand the range of promising 4-amino-1,2,4-triazole-3-thione derivatives.

Hollongdione is the first recorded example of the occurrence of a dammarane hexanor-triterpene in nature possessing antiviral and cytotoxic activity. Its simple one-stage transformation into compounds with terminal alkyne and vinyl chloride fragments via the interaction with phosphorus halides is reported. The copper(I)-catalyzed Mannich reaction of 3-oxo-22,23,24,25,26,27-hexanor-dammar-20(21)-in 3 led to a series of aminomethylated products, while 17-carboxylic acid was obtained by ozone oxidation of 3-oxo-22,23,24,25,26,27-hexanor-dammar-20-chloro-20(21)-en 4; the following direct amidation of the latter has been developed. The structures of all new molecules were established by spectroscopic studies that included 2D NMR correlation methods; the molecular structures of compounds 2–5 were determined by X-ray analysis. [ABSTRACT FROM AUTHOR]

This study includes the preparation and characterization of new compound (4-bromo-5-(N-((4- chlorophenyl) (1,1-dioxide-3-oxobenzo isothiazol-2(3H)-yl)methyl)sulfamoyl)-2-((furan2-ylmethyl)amino)benzoic acid) from the reaction of furosemide, Saccharin and p-bromo benzaldehyde in a molar ratio 1:1:1 in ethanol. All the complexes are prepared from the reaction of Mannich bases with metal nitrate salts of transition metals such as Co, Ni, Cu and Zn in equimolar ratio (1:1) in ethanol solvent. The prepared compounds were characterized by elemental analysis (C.H.N.S), H-NMR, FT-IR, molar conductivity and magnetic sensitivity were determined. The results showed that furosemide derivatives bidentate are coordinated by nitrogen and oxygen atoms with metal, giving tetrahedral geometry. The antibacterial activity was studied for ligands and their complexes using the agar diffusion method. All the prepared compounds were studied and applied to two types of bacteria at different concentrations. It was showed, that the obtained complexes demonstrate a higher inhibitory effect on Staphylococcus aureas bacteria than on Pseudomonas aeruginosa bacteria. [ABSTRACT FROM AUTHOR]

Over the past 20 years, there has been a notable rise in the incidence of invasive bacterial infections. This increase has been mostly linked to the growth of drug‐resistant bacteria. Tetrazoles have been considered as promising antibacterial agents and their effectiveness may be enhanced by hybridization with other antibacterial pharmacophores. In this work, a series of tetrazole hybrids (1‐6) containing oxazepane and pyrazole rings as well as Mannich bases (7,8) were synthesized via the Schiff and Mannich reactions, respectively. The compositions were proven spectroscopically using infrared spectra, proton (1H) and carbon‐13 (13C) nuclear magnetic resonance spectra and elemental analyses. Moreover, the pharmacokinetic properties viz Absorption, Distribution, Metabolism and Excretion (ADME) were predicted in silico using SwissADME server. Compounds 1,2 and 4–6 attaining the best drug‐likeness properties were screened for their antibacterial activities against Staphylococcus epidermidis and Streptococcus mutans at different concentrations in comparison with tetracycline and amikacin, respectively. Afterwards, a molecular docking study was performed to explore the potential binding patterns of the new antibacterial compounds. Collectively, the tetrazole hybrids 4 and 5 have been found to have higher inhibitory potencies compared to tetracycline, serving them as potential antibacterial candidates which can be further optimized in the future. [ABSTRACT FROM AUTHOR]

We have prepared a bis(compartmental) Mannich base ligand H4L (1,4,8,11-tetraaza-1,4,8,11-tetrakis(2-hydroxy-3-methoxy-5-methylbenzyl)cyclotetradecane) specifically designed to obtain bis(TMIILnIII) tetranuclear complexes (TM = transition metal). In this regard, we have succeeded in obtaining three new complexes of the formula [Zn2(μ-L)(μ-OAc)Dy2(NO3)2]·[Zn2(μ-L)(μ-OAc)Dy2(NO3)(OAc)]·4CHCl3·2MeOH (1) and [TM2(μ-H2L)2(μ-succinate)Ln2(NO3)2] (NO3)2·2H2O·6MeOH (TMII = Zn, LnIII = Dy (2); TMII = Co, LnIII = Dy (3)). Compound 1 contains two different bis(ZnDy) tetranuclear molecules that cocrystallize in the structure, in which acetato bridging ligands connect the ZnII and DyIII ions within each ZnDy subunit. This compound does not exhibit slow magnetic relaxation at zero field, but it is activated in the presence of an applied dc magnetic field and/or by Dy/Y magnetic dilution, showing two relaxation processes corresponding to each of the two different bis(ZnDy) units found in the structure. As revealed by the theoretical calculations, magnetic relaxation in 1 is single-ion in origin and takes place through the first excited state of each DyIII ion. When using the succinato dicarboxylate bridging ligand instead of acetate, compounds 2 and 3 were serendipitously formed, which have a closed structure with the succinate anion bridging two ZnDy subunits belonging to two different ligands. It should be noted that only compound 2 exhibits slow relaxation of magnetization in the absence of an external magnetic field. According to experimental and theoretical data, 2 relaxes through the second excited Kramers doublet (Ueff = 342 K). In contrast, 3 displays field-induced SMM behaviour (Ueff = 203 K). However, the Co/Zn diluted version of this compound 3Zn shows slow relaxation at zero field (Ueff = 347 K). Ab initio theoretical calculations clearly show that the weak ferromagnetic coupling between CoII and DyIII ions is at the origin of the lack of slow relaxation of this compound at zero field. Compound 2 and its diluted analogues 2Y and 3Zn show hysteresis loops at very low temperature, thus confirming their SMM behaviour. Finally, compounds 1 and 2 show DyIII based emission even at room temperature that, in the case of 2, allows us to extract the splitting of the ground 6H15/2 term, which matches reasonably well with theoretical calculations. [ABSTRACT FROM AUTHOR]

Aromatic polyimides have attracted wide attentions in fields of aerospace, microelectronics and defense applications due to their outstanding thermal and mechanical performances. However, the rigidity originating from the imide structure attached with an aromatic ring causes difficulties in processing. In this study, we synthesized two ortho-phthalimide functional benzoxazine monomers with additional cross-linkable groups (including both furan and alkynyl). An ortho-phthalimide functional phenol, 2-(2-hydroxyphenyl) isoindole-1,3-dione (oPP), was obtained by reacting o-aminophenol and phthalic anhydride in acetic acid. Two monofunctional ortho-phthalimide containing benzoxazine monomers (oPP-fa and oPP-pa) were then synthesized using the Mannich reaction based on raw materials of oPP, furfurylamine/propargylamine and paraformaldehyde in toluene. The structures of benzoxazine monomers were confirmed by FT-IR and 1H NMR spectroscopies. We also investigated effects of cross-linkable functionalities on curing behaviors as well as their corresponding polymerization mechanisms. The activation energies of oPP-fa and oPP-pa were calculated by Kissinger and Ozawa equations based on DCS measurements with different heating rates. It demonstrates that the exothermic peak temperature of oPP-pa is located at 178.5 °C, which is much lower than that of oPP-fa (223.3 °C). The alkyne group in oPP-pa plays a catalytic effect role in reducing the ring-opening polymerization temperature of the oxazine ring. Moreover, the thermogravimetric analyzer (TGA) was used to evaluate thermal properties of the obtained polybenzoxazine thermosets. Both thermosets exhibited improved thermal stability compared with some other reported monobenzoxazine-derived polybenzoxazines. [ABSTRACT FROM AUTHOR]

In the present study, we use knipholone as a prototype molecule to identify new anti-infective agents. Since knipholone is insoluble in water, which would have a detrimental effect on its bioavailability and efficacy, we synthesized knipholone Mannich base derivatives (2–4) that have better predicted solubility and investigated their in vitro antimicrobial activity against eight pathogenic bacterial and fungal strains. The chemical structures of compounds 1–4 were elucidated from their 1H and 13C NMR data, and their antimicrobial activity evaluation was carried out by a broth microdilution MTT assay. Compound 3 exhibited the strongest efficacy against Staphylococcus epidermidis, with MIC value of 9.7 µg/mL. While 4 exhibited the best activity against Staphylococcus aureus, with an MIC value of 19.5 µg/mL, and was the only one to significantly inhibit the fungus Trichophyton mentagrophytes (MIC = 78.2 µg/mL). The study provides evidence for the antibacterial activity of aminoalkyl derivatives of knipholone. [ABSTRACT FROM AUTHOR]

Previous studies have shown that some lamellarin-resembling annelated azaheterocyclic carbaldehydes and related imino adducts, sharing the 1-phenyl-5,6-dihydropyrrolo[2,1-a]isoquinoline (1-Ph-DHPIQ) scaffold, are cytotoxic in some tumor cells and may reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). Herein, several novel substituted 1-Ph-DHPIQ derivatives were synthesized which carry carboxylate groups (COOH, COOEt), nitrile (CN) and Mannich bases (namely, morpholinomethyl derivatives) in the C2 position, as replacements of the already reported aldehyde group. They were evaluated for antiproliferative activity in four tumor cell lines (RD, HCT116, HeLa, A549) and for the ability of selectively inhibiting P-gp-mediated MDR. Lipophilicity descriptors and molecular docking calculations helped us in rationalizing the structure–activity relationships in the P-gp inhibition potency of the investigated 1-Ph-DHPIQs. As a main outcome, a morpholinomethyl Mannich base (8c) was disclosed which proved to be cytotoxic to all the tested tumor cell lines in the low micromolar range (IC50 < 20 μM) and to inhibit in vitro the efflux pumps P-gp and MRP1 responsible for MDR, with IC50s of 0.45 and 12.1 μM, respectively. [ABSTRACT FROM AUTHOR]

The interaction of 7-hydroxyneoflavone-6-enamino ketone with 8-dialkylamino-7-hydroxy-3-hetarylbenzopyran-2- and 4-ones led to the formation of 10-methyl-4-phenyl-2H,6H-pyrano[3,2-g]-chromen-2,6-dione, which incorporated coumarin or chromone fragments at C-7 using a methylene linker. The recyclization of 7-[3-(1,3-benzothiazol-2-yl)-7-hydroxy-2-oxo-2H-8-chromenylmethyl]-10-methyl-4-phenyl-2H,6H-pyrano[3,2-g]chromene-2,6-dione and 7-[6-ethyl-7-hydroxy-3-(4-methyl-1,3-thiazol-2-yl)-4-oxo-4H-8-chromenylmethyl]-10-methyl-4-phenyl-2H,6H-pyrano[3,2-g]chromene-2,6-dione was investigated under the influence of N,N- and N,O-binucleophiles. [ABSTRACT FROM AUTHOR]

Oxidovanadium(V) complex [VVO{Hen(3,5-dcp)4}] (where H4en(3,5-dcp)4, is a Mannich base synthesized from ethylenediamine, paraformaldehyde and 2,4-dichlorophenol) has been anchored onto chloromethylated polystyrene (PS–Cl) cross-linked with divinylbenzene to obtain [VVO{en(3,5-dcp)4}]@PS (@ refers to anchoring of complex onto polymer), a heterogeneous compound. Both of the synthesized (homogeneous as well as heterogeneous) vanadium compounds, after characterization, have been explored as biomimicking model catalysts for the type II copper site in phenoxazinone synthase. These compounds catalyze the oxidative condensation of o-aminophenol (OAP) into 2-aminophenoxazine-3-one (APX) by utilizing aqueous hydrogen peroxide in acetonitrile. Various reaction conditions like amounts of catalyst and oxidant, and temperature have been optimized to obtain maximum yield of APX. The polymer-immobilized complex demonstrates excellent catalytic activity, giving 96% yield of 2-aminophenoxazine-3-one under the optimized reaction conditions selectively. Its homogeneous analogue i.e. [VVO{Hen(3,5-dcp)4}], is also active and exhibits 83% yield. The heterogeneous catalyst i.e. [VVO{en(3,5-dcp)4}]@PS is stable, recyclable and reusable. [ABSTRACT FROM AUTHOR]

Nitrothiazole derivatives have been reported to exhibit activity against aerobic, anaerobic, and microaerophilic bacteria. This activity profile makes the nitrothiazole compound class an ideal lead source against Mycobacterium tuberculosis, which flourishes in varied environments with different oxygen concentrations. In this work, we investigated six nitrothiazole derivatives for antitubercular activity. The compounds exhibited potent activity, with compounds 9 and 10 possessing an equipotent MIC90 value of 0.24 µM. The compounds were investigated for cytotoxicity against HEK293 cells and hemolysis against red blood cells, and they demonstrated no cytotoxicity nor hemolytic effects, suggesting they possess inherent antitubercular activity. [ABSTRACT FROM AUTHOR]

A synthetic approach to N-[3-(hetero)aryl-3-oxoprop-1-yl]sulfonamides by N-alkylation of sulfanilamide with structurally diverse ketone Mannich base hydrochlorides is being reported. This scarcely explored synthetic strategy that involves aminomethylated ketones as starting materials has afforded novel compounds, potentially useful as inhibitors of carbonic anhydrases, with moderate to good yields. [ABSTRACT FROM AUTHOR]

AbstractThe study investigated the corrosion-inhibitory properties of three synthetic triazole Mannich bases on C1018 carbon steel using various electrochemical techniques. The inhibitors, namely 4-amino-2-[(4-methylpiperazin-1-yl)methyl]-5-(pyridin-4-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (4MPT), 4-amino-2-[(piperidin-1-yl)methyl]-5-(pyridin-4-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (PPT) and 4-amino-2-[(morpholin-4-yl)methyl]-5-(pyridin-4-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (MPT), demonstrated the high inhibition efficiencies of 92.8%, 93.3% and 92.6%, respectively, and adhered to the Langmuir adsorption isotherm. The inhibitors also functioned as mixed-type inhibitors and improved the protective layer on the metal surface. The study also utilized scanning electron microscopy - energy dispersive x-ray (SEM-EDX) analysis to examine the surface morphology of the uninhibited and inhibited carbon steel specimens. Furthermore, density functional theory (DFT) was utilized for theoretical calculations, which corroborated with experimental measurements.

A number of compounds with various structures was obtained by the reaction of 2-propenylphenol, formaldehyde, and methylamine. The treatment of the condensation products with HBr resulted in their quaternary ammonium salts. The anticorrosion and biocidal properties and also antimicrobial activity of the obtained compounds and their ammonium salts in relation to S. aureus, E. coli, C. albicans, Sh. flexneri, S. enterica, and A. niger strains were studied. It was found that the ammonium salts have higher bactericidal properties than the standard (amoxicillin). The results obtained were also confirmed by electron microscopy studies. [ABSTRACT FROM AUTHOR]

Mannich bases are interesting class of molecules thanks to their various pharmacological properties. This paper presents the synthesis and characterization of eugenol derivatives following Mannich condensation. The in vitro antituberculosis activity of the synthesized derivatives was evaluated by the Resazurin microtiter assay (REMA). The 2,2′‐diphenyl‐1‐picrylhydrazyl (DPPH) free radical scavenging and ferrous cation (FeCl2) chelating tests were used to estimate the antioxidant capacity. All eugenol Mannich bases inhibited the Mycobacterium tuberculosis (Mtb) H37Rv growing. Those of 2‐dimethylaminomethyl‐6‐methoxy‐4‐propenylphenol (1) and 2‐methoxy‐4‐propenyl‐6‐pyrrolidinylmethylphenol (4) were the most active at 10 μg/mL. Additionally, significant antioxidant profile was exhibited by the synthesized derivatives, especially for 2‐dicyclohexylaminomethyl‐6‐methoxy‐4‐propenylphenol (5) that showed an antiradical activity of EC50=20 μg/mL, twice as strong as that of eugenol precursor, and for 2‐methoxy‐6‐methylpiperazinylmethyl‐4‐propenylphenol (3) and compound 4, which were promising iron chelators with EC50 of 0.016 and 0.018 mg/mL, respectively, better than EDTA standard. The molecular docking experiments on two different antituberculosis receptors showed excellent binding affinity of compounds 4 and 5 into the active site of pantothenate kinase (PanK, type I), suggesting PanK as potential molecular target. These encouraging findings showed the importance of Mannich reaction for the development of antitubercular candidates and the improvement of natural products bioactivity. [ABSTRACT FROM AUTHOR]

Twelve novel compounds (Phenylenediamine side chain modified 4‐Aminoquinoline Mannich Bases) were synthesized and characterized by using a variety of analytical and spectroscopic methods. All the synthesized compounds were screened for in‐vitro antimalarial activity on 3D7 strain of Plasmodium falciparum. Synthesized compounds showed MIC values between 1.9 and 125 μg/ml in antimalarial screening (in‐vitro). Two compounds (MIC=1.9 μg/ml or 1.953± ${\pm }$ 0.10 μM and 7.8 μg/ml or 2.200± ${\pm }$ 0.08 μM) were found most potent against chloroquine sensitive 3D7 strain of Plasmodium falciparum which is comparable to standard drug chloroquine (MIC=0.4 μg/ml or 0.106± ${\pm }$ 0.01 μM). [ABSTRACT FROM AUTHOR]

Twenty‐one new coumarin Mannich base derivatives (11a‐u) were synthesized, which exhibited antiproliferation activities in HepG2 (liver cancer), A549 (lung cancer), MCF‐7 (breast cancer), and HT‐29 (colon cancer). Most of the target compounds showed the most potent activity against HepG2 cells compared with other cancer cells, compound 11g showed the strongest antiproliferative activity (2.10 μM) against HepG2, even superior to the positive control drug 5‐FU(5.49 μM). The nitric oxide (NO) release of all compounds in HepG2 cells was determined, of which compound 11g showed high levels of NO release (10.8 μM). Notably, the solubility of compound 11g increased 13‐fold compared with the lead 8. The preliminary cytotoxicity studies suggest that 11g had little effect on LO2 cells(normal liver cells, >50 μM). The effect of compound 11g on the apoptosis of HepG2 cells was also studied, and the results showed that the induction effect of compound 11g on apoptosis is a concentration‐dependent manner. Our results indicate that compound 11g might be a promising lead for further studies. [ABSTRACT FROM AUTHOR]

Oleanolic and glycyrrhetic acids alkyne derivatives were synthesized as a result of propargylation of the indole NH‐group condensed with the triterpene A‐ring, the following aminomethylation led to a series of Mannich bases. The synthesized compounds were tested for their potential inhibition of influenza A/PuertoRico/8/34 (H1N1) virus in Madin‐Darby canine kidney (MDCK) cell culture and SARS‐CoV‐2 pseudovirus in baby hamster kidney‐21‐human angiotensin‐converting enzyme 2 (BHK‐21‐hACE2) cells. Mannich bases of oleanolic and glycyrrhetic acids N‐propargylated indoles 7, 8, and 12 were the most efficacious against influenza virus A with IC50 7–10 μM together with a low toxicity (CC50 > 145 μM) and high selectivity index SI value 20. Indolo‐oleanolic acid morpholine amide Mannich base holding N‐methylpiperazine moiety 9 showed anti‐SARS‐CoV‐2 pseudovirus activity with EC50 value of 14.8 μM. Molecular docking and dynamics modeling investigated the binding mode of the compounds 7 and 12 into the binding pocket of influenza A virus M2 protein and compound 9 into the RBD domain of SARS‐CoV‐2 spike glycoprotein. [ABSTRACT FROM AUTHOR]

Over the past twenty years (1998–2023), extensive research has focused on the synthesis and biological activity of Mannich base derivatives of flavonoids (FMBD), which have demonstrated exceptional properties towards organic and bioorganic molecules. Several research groups have reported the pharmacological potential of these flavonoid derivatives, including antioxidant and antiviral activities, as well as their ability to inhibit AChE and exhibit anticancer properties. Moreover, the unique characteristic of forming stable complexes with biomolecules positions flavonoid derivatives as valuable assets in the realm of biology and drug discovery. In this extensive review, we′ve meticulously analyzed over seventy six distinct research studies on this subject. Our aim is to provide a succinct overview of the wide‐ranging applications of flavonoid derivatives coupled with amines. Furthermore, we explore the promising horizons and potential innovations in this field. It's essential to highlight that these derivatives display no discernible signs of toxicity or eliciting immune responses, making them even more attractive for biopharmaceutical applications. Undoubtedly, the utilization of flavonoid derivatives combined with amines as crucial biopharmaceutical agents is poised for significant expansion in the forthcoming years. [ABSTRACT FROM AUTHOR]

The Mannich reaction is commonly used to introduce N atoms into compound molecules and is thus widely applied in drug synthesis. The Mannich reaction accounts for a certain proportion of structural modifications of natural products. The introduction of Mannich bases can significantly improve the activity, hydrophilicity, and medicinal properties of compounds; therefore, the Mannich reaction is widely used for the structural modification of natural products. In this paper, the application of the Mannich reaction to the structural modification of natural products is reviewed, providing a method for the structural modification of natural products. [ABSTRACT FROM AUTHOR]

The study focuses on the synthesis of isatin- barbituric acid compounds through a two-step process. In the first step, using mannich reaction, new derivatives of Isatin are synthesized by reacting Isatin with either barbituric acid, along with formaldehyde. This reaction results in the formation of Isatin-barbituric acid derivative. In the second step, these Isatin derivatives are further reacted with various aniline derivatives to generate new compounds containing Isatin. Spectroscopic methods including FTIR, ¹H NMR, and 13C NMR are used to characterize the produced molecules. The study investigates the biological effects of several of the synthetic chemicals on certain bacterial strains, including Klebsiella pneumoniae and Staphylococcus aureus. The potential antibacterial activities of these substances are evaluated. [ABSTRACT FROM AUTHOR]

A regioselective and trans-diastereoselective method for the preparation of 2-aryl-2,3-dihydro-1H-benzo[f]chromenes based on 2-naphthol Mannich bases as precursors of 1,2-naphthoquinone 1-methides and highly polarized β-(N,N-dimethylamino)styrene was developed. The resulting cycloadducts were transformed into cyclic acetals and hemiacetals as well as introduced into the Cope reaction leading to 2-aryl-1H-benzo[f]chromenes. [ABSTRACT FROM AUTHOR]

Mannich bases are a class of organic compounds usually obtained by the condensation reaction between an amine, a compound with active hydrogens, and an aldehyde. They are versatile intermediates in organic synthesis, and those compounds containing this motif find applications in pharmaceutical, agrochemical, and even material fields since they are widely known for their wide range of biological activities, including antimicrobial properties. Thus, as part of our interest in antifungal agents, this narrative review aimed to gather information from the literature on the synthesis of various representative Mannich-base-containing compounds, particularly centered on those exhibiting antifungal properties. In this context, the compilation indicated that Mannich bases could be considered as a relevant toxophore/pharmacophore by incorporating heterocyclic moieties to be implemented for the design of new antifungal agents, given its proven efficacy against phytopathogens, other opportunistic human pathogens, and some dermatophytic fungal species, which can be further exploited as agrochemical agents or in medicinal applications to treat fungal infections. The antifungal effect exhibited by Mannich bases conjugated with oxa and/or aza-heterocycles suggests that compounds that have a heterocyclic system attached to the β-amino core are attractive alternatives oriented to the synthesis of novel and helpful antifungal agents. [ABSTRACT FROM AUTHOR]

The study investigated the corrosion-inhibitory properties of three synthetic triazole Mannich bases on C1018 carbon steel using various electrochemical techniques. The inhibitors, namely 4-amino-2-[(4-methylpiperazin-1-yl)methyl]-5-(pyridin-4-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (4MPT), 4-amino-2-[(piperidin-1-yl)methyl]-5-(pyridin-4-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (PPT) and 4-amino-2-[(morpholin-4-yl)methyl]-5-(pyridin-4-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (MPT), demonstrated the high inhibition efficiencies of 92.8%, 93.3% and 92.6%, respectively, and adhered to the Langmuir adsorption isotherm. The inhibitors also functioned as mixed-type inhibitors and improved the protective layer on the metal surface. The study also utilized scanning electron microscopy - energy dispersive x-ray (SEM-EDX) analysis to examine the surface morphology of the uninhibited and inhibited carbon steel specimens. Furthermore, density functional theory (DFT) was utilized for theoretical calculations, which corroborated with experimental measurements. [ABSTRACT FROM AUTHOR]

Mannich bases (8 examples) were synthesized via aminomethylation of fusidane propargyl esters. In vitro antimicrobial screening against key ESKAPE pathogens showed that the fusidic acid based Mannich products exhibit a high antimicrobial effect against Gram-positive bacteria Staphylococcus aureus and the fungus Cryptococcus neoformans. Moreover, the cytotoxic effect of fusidic acid and its analogs, which showed high antibacterial activity, was determined by MTT assay on cancer HepG2, HCT-116, SH-SY5Y, MCF-7, A549 and conditionally normal cells HEK293. A remarkable cytotoxic activity of fusidic acid propargyl ester and its aminomethylene derivatives against cancer and nontumoral HEK293 cells with IC50 values within 4.2–25 µM was found. [ABSTRACT FROM AUTHOR]

Nitrothiazole derivatives have been reported to exhibit activity against aerobic, anaerobic, and microaerophilic bacteria. This activity profile makes the nitrothiazole compound class an ideal lead source against Mycobacterium tuberculosis, which flourishes in varied environments with different oxygen concentrations. In this work, we investigated six nitrothiazole derivatives for antitubercular activity. The compounds exhibited potent activity, with compounds 9 and 10 possessing an equipotent MIC90 value of 0.24 µM. The compounds were investigated for cytotoxicity against HEK293 cells and hemolysis against red blood cells, and they demonstrated no cytotoxicity nor hemolytic effects, suggesting they possess inherent antitubercular activity.

Mannich bases are a class of organic compounds usually obtained by the condensation reaction between an amine, a compound with active hydrogens, and an aldehyde. They are versatile intermediates in organic synthesis, and those compounds containing this motif find applications in pharmaceutical, agrochemical, and even material fields since they are widely known for their wide range of biological activities, including antimicrobial properties. Thus, as part of our interest in antifungal agents, this narrative review aimed to gather information from the literature on the synthesis of various representative Mannich-base-containing compounds, particularly centered on those exhibiting antifungal properties. In this context, the compilation indicated that Mannich bases could be considered as a relevant toxophore/pharmacophore by incorporating heterocyclic moieties to be implemented for the design of new antifungal agents, given its proven efficacy against phytopathogens, other opportunistic human pathogens, and some dermatophytic fungal species, which can be further exploited as agrochemical agents or in medicinal applications to treat fungal infections. The antifungal effect exhibited by Mannich bases conjugated with oxa and/or aza-heterocycles suggests that compounds that have a heterocyclic system attached to the β-amino core are attractive alternatives oriented to the synthesis of novel and helpful antifungal agents.

This paper deals with the evaluation of novel imidazole molecules for their antimicrobial and larvicidal activities. A series of imidazole derivatives 1(a–f) and 2(a–e) were prepared by the Mannich base technique using a Cu(II) catalyst. The Cu(phen)Cl2 catalyst was found to be more effective than other methods. FTIR, elemental analyses, mass spectrometry, 1H NMR, and 13C NMR spectroscopy were performed to elucidate the structures of the synthesised compounds. Antimicrobial and larvicidal activities were investigated for all compounds. The antibacterial activity of compounds (2d) and (2a) were highly active in S.aureus (MIC: 0.25 μg/mL) and K.pneumoniae (MIC: 0.25 μg/mL) compared to ciprofloxacin. Compound (1c) was significantly more effective than clotrimazole in C.albicans (MIC: 0.25 μg/mL). Molecular docking studies of compound 2d showed a higher binding affinity for the 1BDD protein (− 3.4 kcal/mol) than ciprofloxacin (− 4.4 kcal/mol). Compound 1c had a higher binding affinity (− 6.0 kcal/mol) than clotrimazole (− 3.1 kcal/mol) with greater frontier molecular orbital energy and reactivity properties of compound 1c (∆E gap = 0.13 eV). The activity of compound 1a (LD50: 34.9 μg/mL) was more effective in the Culex quinquefasciatus than permethrin (LD50: 35.4 μg/mL) and its molecular docking binding affinity for 3OGN protein (− 6.1 kcal/mol). These newly synthesised compounds can act as lead molecules for the development of larvicides and antibiotic agents. [ABSTRACT FROM AUTHOR]

The optimized synthesis of [5-oxo-4,4-diphenylimidazolidin-2-ylidene]cyanamide, which is known as 2-cyanoguanidinophenytoin (CNG-DPH) (3), and (imidazo[4,5-d]imidazole-2,5-diylidine)dicyanamide (4) has been reported in the present work. Furthermore, new Mannich bases derived from CNG-DPH were synthesized via its reaction with formaldehyde and using the corresponding amines, piperidine (base 5), and morpholine (base 6). Also, the antimicrobial activity and X-ray crystal structures for CNG-DPH and their Mannich bases were studied. The bases 3 and 6 crystallized in a monoclinic system; the crystal structure of 3 containing four molecules in the unit cell with a P21/c space group. The unit cell of 6 has eight molecules with a C2/c space group. The inter and intra hydrogen bond contacts packed and stabilized both of the structures. The morpholine ring of base 6 demonstrated a distinctive chair configuration. Mannich bases 5 and 6 showed promising antimicrobial effects. base 4 has a greater percentage for in vitro cytotoxicity (IC50) against normal cells, whereas 3 has the lowest ratio. [ABSTRACT FROM AUTHOR]

Based on benzylthioctane-2-ol, heterocyclic amines (piperidine, morpholine, hexamethyleneimine), and formaldehyde, new Mannich bases were synthesized. The reaction was carried out at a temperature of 45-500C for 3-4 h. in an equimolar ratio of starting compounds. The yield of target products was 70-74%. The physicochemical data of the synthesized compounds were determined. The composition and structure of the target products were confirmed by elemental analysis, IR and 1H NMR spectroscopy. Their influence on the vital activity of sulfate-reducing bacteria of the Desulfovibrio desulfiricans type at three concentrations (25, 50, 100 mg/l) was studied. The obtained compounds showed high bactericidal properties, since 1% solutions of these compounds in isopropyl alcohol at a concentration of 100 mg/l showed a 100% bactericidal effect. Given that the aminomethoxy derivatives of 1-benzylthiooctane affect bacteria at very low concentrations, they can be proposed as effective inhibitors of sulfate reducing bacteria (SRB). [ABSTRACT FROM AUTHOR]

In this research article, we investigate the corrosion inhibition properties of two novel morpholinyl mannich bases namely 3-morpholino-1-phenylpropan-1-one (MB1) and 3- morpholino-1-phenyl-3-(pyridin-4-yl) propan-1-one (MB2). To establish a link between their corrosion inhibition efficacy and molecular characteristics, we employ a comprehensive approach involving the calculation of DFT-derived global and local reactivity parameters, as well as structure-activity relationship (SAR) indices. The obtained values of the global reactivity indices including dipole moment, energy gap, hardness, and softness show a positive correlation with the experimental data earlier reported. Fukui functions give a comprehensive reactive scheme exhibiting the atoms responsible for the electronic transfer. SAR parameters such as molecular volume (V), surface area (SA), and the polarizability (α) were found to be in good accordance with the experimental inhibition effectiveness order. [ABSTRACT FROM AUTHOR]

1-((4-chlorophenyl) (piperazine) methyl) indoline-2, 3-dione (2) were synthesized by using Mannich bases from reacted of isatin (1), p-chlorobenzaldehyde, and piperazine in sodium ethoxide solution. Compounds (1, 2) are used as starting material to prepare many heterocyclic compounds such as: 1-(substituted-piperazine-methyl) indoline-2, 3-dione (3-5), 2-((3-oxo-3H-indole) oxy) acetamide (6), 1, 4-oxazino[2, 3-b]indol-2(3H)-one (7), 2-((1-substituted-2-oxoindolin-3-ylidene) amino) benzoic acid (8-10), 1-(2-bromoacetyl or quinoxaline) indoline-2, 3-dione (11, 12), 2-(dioxoindoline)-2-oxoethyl-carbamimidothioate (13), 1, 3-thiazino[4, 5-b] quinoxaline-indoline-dione (14), imidazo[4, 5-b]quinoline-2-oxoindoline (15), 1, 2, 4-triazino-imidazo[4, 5-b]quinoline-indoline (16), 1, 2, 4, 5-tetrazinoimidazo [4, 5-b] quinoline-indoline (17), and benzothieno-triazepino-imidazo[4, 5-b]quinoline-indoline-amino-benzoic acid (18). The new compounds were evidenced by means of numerous spectroscopic analyses for example IR, NMR, mass spectrum and elemental analysis. All of the synthesized compounds in this search were tested and evaluated as antimicrobial agents. Some of the compounds presented the best efficiency as antimicrobial compared with the cefotaxime sodium and nystatin as standard drugs such as [18, 17, 16, 15 and 14], respectively. [ABSTRACT FROM AUTHOR]

Previous studies have shown that some lamellarin-resembling annelated azaheterocyclic carbaldehydes and related imino adducts, sharing the 1-phenyl-5,6-dihydropyrrolo[2,1-a]isoquinoline (1-Ph-DHPIQ) scaffold, are cytotoxic in some tumor cells and may reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). Herein, several novel substituted 1-Ph-DHPIQ derivatives were synthesized which carry carboxylate groups (COOH, COOEt), nitrile (CN) and Mannich bases (namely, morpholinomethyl derivatives) in the C2 position, as replacements of the already reported aldehyde group. They were evaluated for antiproliferative activity in four tumor cell lines (RD, HCT116, HeLa, A549) and for the ability of selectively inhibiting P-gp-mediated MDR. Lipophilicity descriptors and molecular docking calculations helped us in rationalizing the structure–activity relationships in the P-gp inhibition potency of the investigated 1-Ph-DHPIQs. As a main outcome, a morpholinomethyl Mannich base (8c) was disclosed which proved to be cytotoxic to all the tested tumor cell lines in the low micromolar range (IC50 < 20 μM) and to inhibit in vitro the efflux pumps P-gp and MRP1 responsible for MDR, with IC50s of 0.45 and 12.1 μM, respectively.

Isoflavenes have received the greatest research attention among the many groups of phytoestrogens. In this study, various isoflavene-based Mannich bases were selected for their theoretical studies. The purpose of this research was to discover the binding potential of all the designated Mannich bases acting as inhibitors against cancerous proteins EGFR, cMet, hTrkA, and HER2 (PDB codes: 5GTY, 3RHK, 6PL2, and 7JXH, respectively). For their virtual screening, DFT calculations and molecular docking studies were undertaken using in silico software. Docking studies predicted that ligands 5 and 15 exhibited the highest docking score by forming hydrogen bonds within the active pocket of protein 6PL2, ligands 1 and 15 both with protein 3RHK, and 7JXH, 12, and 17 with protein 5GTY. Rendering to the trends in polarizability and dipole moment, the energy gap values (0.2175 eV, 0.2106 eV) for the firm conformers of Mannich bases (1 and 4) replicate the increase in bioactivity and chemical reactivity. The energy gap values (0.2214 eV and 0.2172 eV) of benzoxazine-substituted isoflavene-based Mannich bases (9 and 10) reflect the increase in chemical potential due to the most stable conformational arrangements. The energy gap values (0.2188 eV and 0.2181 eV) of isoflavenes with tertiary amine-based Mannich bases (14 and 17) reflect the increase in chemical reactivity and bioactivity due to the most stable conformational arrangements. ADME was also employed to explore the pharmacokinetic properties of targeted moieties. This study revealed that these ligands have a strong potential to be used as drugs for cancer treatment. [ABSTRACT FROM AUTHOR]

A series of novel Mannich bases were designed, synthesized, and screened for their antimicrobial activity. The target compounds were synthesized from 4-(3-chlorophenyl)-5-(3-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione and different piperazine derivatives. The structures of the products were confirmed by 1H and 13C NMR and elemental analysis. The activity of piperazine derivatives against bacteria (Gram-positive: Staphylococcus epidermidis, Staphylococcus aureus, Micrococcus luteus, Bacillus cereus, and Bacillus subtilis; Gram-negative: Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Proteus mirabilis) and yeasts (Candida glabrata, Candida krusei, and Candida parapsilosis) was determined by the minimum inhibitory concentration and minimum bactericidal concentration values. Significant activity was observed against Gram-positive bacteria, mainly staphylococci (PG7–PG8) and bacteria of the genes of Micrococcus and Bacillus (PG1-3), as well as selected strains of Gram-negative bacteria, including bacteria of the Enterobacteriaceae family (PG7), while all tested compounds showed high fungistatic activity against Candida spp. yeasts, especially C. parapsilosis, with MICs ranging from 0.49 µg/mL (PG7) to 0.98 µg/mL (PG8) and 62.5 µg/mL (PG1-3). In conclusion, the results obtained confirm the multidirectional antimicrobial activity of the newly synthesized piperazine derivatives. Furthermore, in silico studies suggest that the tested compounds are likely to have good oral bioavailability. The results obtained will provide valuable data for further research into this interesting group of compounds. The library of compounds obtained is still the subject of pharmacological research aimed at finding new interesting biologically active compounds. [ABSTRACT FROM AUTHOR]

Bicyclo[3.3.1]nonane system is an important structural motif in many natural compounds. This article describes a short synthetic route to the bicyclo[3.3.1]nonane system via aldol condensation. The proposed strategy is based on the use of cyclohex-2-en-1-ones containing an additional carbonyl group in the side chain as a key precursor. The approach showed good results for compounds with electron-donating groups in aromatic substituents. An obvious advantage of such synthesis of bicyclo[3.3.1]nona-3,6-dien-2-ones is that it involves two steps and requires only two building blocks, namely a Mannich base and ethyl acetoacetate. [ABSTRACT FROM AUTHOR]

A series of new (E)-7-hydroxy-8-(amino-methyl)-4-styryl-2H-chromen-2-one derivatives has been synthesized. The protocol involves the reaction of Knoevenagel condensation product of 7-hydroxy-4-methylcoumarin with secondary aliphatic amine and equimolar formaldehyde under Mannich conditions. In vitro antimycobacterial activity of the developed compounds has been assessed against Mycobacterium smegmatis, a surrogate of the causal organism of tuberculosis Mycobacterium tuberculosis, by broth dilution assay. Among the tested compounds, 7a-f shows MIC value against the concentration 1000μg/mL. [ABSTRACT FROM AUTHOR]

4-hydroxy 3-methoxy benzaldehyde (Vanillin) is an aromatic phenolic aldehyde with unique chemical properties and pharmacological impact. Because of its potent nature, it acts as a lead for drug discovery and development techniques. Heterocyclic compounds with vanillin moiety were efficacious and thrive against many emerging infectious diseases, which can also lead to develop numerous fused heterocyclic vanillin derivatives and various heterocyclic compounds such as pyrimidines, quinoxalines, imidazoles or thiazoles. Greener-mediated synthesis is a sustained chemical reaction used to synthesize hazardless vanillin derivatives with a high yield of product in desired time. Due to its several reasonable modifications with high bioactivity, vanillin moiety can be used to develop various potent derivatives like vanillin-based ferrocenyl chalcone derivatives, vanillin-hydrazone derivatives, Schiff base and Mannich base-based derivatives, pyrazoline vanillin-based derivatives, triazole-based vanillin derivatives and vanillin hybrids plays a crucial role in the coordination chemistry. These derivatives exhibited plenty of biological applications, which include anticancer, antioxidant, antibacterial, antitubercular, antimalarial, antiviral, anti-inflammatory, anti-Alzheimer and anti-diabetic effects. Hence, this review focuses on the significance of vanillin derivatives responsible for biological activity. [ABSTRACT FROM AUTHOR]

The present work aimed to synthesize new phenol resins via incorporation of structural modification through introducing new phenolic compounds containing cyclic imide moiety in reaction with formaldehyde. The synthesis of these new resins involved three steps. First, one of the three N- (hydroxyphenyl)tetrabromophtalamic acids 1-3 were processed via a reaction between tetrabromophthalic anhydride and aminophenols. Amic acids 1-3 were dehydrated in the second step by smelting, producing the identical N- (hydroxyphenyl)tetrabromophthalimides 4-6. The new imides represent the new phenolic component that was presented in condensation reaction with formaldehyde in the third step, creating the target phenolic resins 7-9. The work also involved curing the new resins through esterification of phenolic OH groups by treatment with benzoyl chloride. The chemical structures of prepared compounds were confirmed according to FT-IR, ¹H NMR, and 13C NMR spectral data. As a conclusion, the present work supply of new phenolic resins and the presence of the cyclic imide (tetrabromophthalimide) moiety in their structures exhibit high softening points and resistance to solubility, which fit with some applications, while subsequent curing through esterification exhibits better solubility and lower softening points, which fit with other applications. [ABSTRACT FROM AUTHOR]

The copper and nickel complexes of two tetradentate ligands derived from bis(aminophenol) and bis(phenol) architectures connected by an oxamate linker were isolated. Depending on the metal and ligand, the complex is isolated with either an intact (deprotonated) ligand (12−), one‐electron oxidized ligand (2−) or quinone form (3). Surprisingly, the Mannich base is easier to oxidize than the amidophenol derivatives. The complexes were characterized by X‐ray diffraction, cyclic voltammetry, UV‐Vis‐NIR and EPR spectroscopies. Complex 1 shows two reversible oxidation waves assigned to the successive iminosemiquinone/aminophenolate redox systems. Complex 2− shows an intense NIR feature, as well as an EPR signal at giso=2.043, consistent with a metallic contribution to the main ligand radical SOMO. Complex 3 shows the typical feature of an isolated Cu(II) complex. Spectro‐electrochemistry coupled to DFT calculations demonstrate a ligand‐centered oxidative redox chemistry for all the complexes. [ABSTRACT FROM AUTHOR]