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The effects of the number of imidazoline ring and the length of alkyl group chain of imidazoline derivatives were investigated using quantum chemical calculation, molecular dynamics simulation and experimental techniques. Three corrosion inhibitors including Symmetrical lauric acid imidazoline (SAI), Tetracyclic lauric acid imidazoline (LAI), and Symmetric stearic acid imidazoline (SPI) were synthesized and their inhibition performance was evaluated using weight loss measurement, electrochemical techniques and surface characterization. The results show that SAI and LAI with the same length of alkyl group chain, LAI with more imidazoline rings could supply a better inhibition performance since the increase of active sites. The increase of active sites attached to the metal surface may also change the distribution of corrosion inhibitor, which could limit inhibition performance improvement. While, SAI and SPI with the same number of imidazoline rings, SPI with longer alkyl group chain shows a better inhibition efficiency due to the better hydrophobic performance of alkyl groups. Among the three inhibitors, SPI show the best inhibition performance, indicating that the alkyl group chain length affects the inhibition performance more obvious than the number of the imidazoline rings.

Imidazoline receptor antisera selected/Nischarin was proposed several years ago as the functional entity for the I1 medullary receptors (I1Rs) targeted, together with α2-adrenoceptors, by the centrally acting antihypertensive drugs, such as clonidine. The objective of this study was to test this assumption using a pyrroline analog of clonidine, LNP599, which, unlike clonidine and related compounds, displays high selectivity toward I1Rs. Cardiovascular effects of LNP599 (3 mg/kg intravenous) were evaluated in anesthetized, artificially ventilated nischarin mutant rats expressing a truncated form of nischarin lacking the putative imidazoline binding site. LNP599 induced a rapid and pronounced fall in arterial blood pressure in wild-type animals (-42.7% ± 11.0% after 15 minutes), associated with a ≈30% heart rate reduction. Similar effects were obtained in homozygous and heterozygous nischarin mutant rats. The observation that the hypotensive response to I1R activation is not affected by the absence of the putative imidazoline binding site on nischarin strongly suggests that nischarin cannot be regarded as the functional I1R. Carbohydrate regulation was improved in nischarin mutant rats, further supporting the conclusion that nischarin and I1R are 2 distinct molecular entities.

p53-MDM2/MDMX interaction inhibitors represent the prospective agents for targeted anticancer therapy in tumors expressing wild-type p53 protein. Imidazoline-based MDM2-targeted inhibitors of such type, nutlins, contain halogen-substituted phenyl rings, which dramatically decrease the solubility of compounds in water. The addition of suitable hydrophilic substituents in benzene rings and to imidazoline nitrogen can improve the compound’s water solubility. In this study, we have synthesized novel hydrophilic cis-2,4,5-tris(alkoxyphenyl)imidazolines and studied the influence of N-sulfonyl substituent on protein-protein interaction compared to unsubstituted alkoxy-compounds. The biological activity of the obtained compounds was studied using Western blot analysis on A549, RKO and SH-SY5Y cancer cell lines. It was found that the derivatives are able to inhibit MDM2/MDMX-p53 interaction, promote p53 stabilization and induce p21 expression in the concentrations from 500 nM.

The inhibition performance of a mixture of an imidazoline quaternary ammonium salt (IM) and octylphenol polyoxyethene ether (OP) (IMO) toward carbon dioxide (CO2) corrosion of L245 steel in 3 wt% sodium chloride (NaCl) solution at 25°C was studied using electrochemical measurements. Notably, the inhibition efficiency of the IMO inhibitor stayed steadily in the long-term immersion test, and the inhibition efficiency increased with time. This was attributed to the improved electron-transfer performance between the inhibitor molecules and the metal surface. OP molecules promoted electrons to the metal, while IM molecules accepted electrons from the metal. The interactions between the inhibitor molecules and metal surface were enhanced, and the relative bonding intensities were improved. Moreover, the adsorption configurations of the mixture of IM and OP facilitated the improvement of the thickness and the compactness of the inhibitor layer. OP and IM showed a good synergistic inhibition effect.

Attempts to extend the hydrated imidazoline ring expansion (HIRE) strategy to a series of diarene-fused [1,4]diazepinones (earlier applied successfully to bis-pyrido substrate nevirapine) did not result in ring expansion but, rather, led to 2-aminoethyl side chain expulsion. This seeming setback (setting the limitations to the HIRE methodology substrate scope) led to the discovery of selective dopamine D2 ligands with elements of structure–activity relationships.

Increased microglial NADPH oxidase (NOX2) production may make an important contribution to the increased incidence and severity of ischemic stroke associated with diabetes. Imidazoline receptors are closely associated with neuroprotection, but the neuroprotective effects of the selective I2-imidazoline receptor ligand 2-(2-benzofuranyl)-2-imidazoline (2BFI) in diabetes has not been established. The effect of 2BFI on microglial NOX2 production was investigated using a co-culture of neurons and microglia, and the effect on cerebral ischemia-reperfusion (IR) injury was determined in diabetic rats. Garcia neurological scores, brain infarct volumes, brain water content, TUNEL staining, blood-brain barrier, and immunofluorescent labeling for microglia were evaluated. Western blots were used to determine gp91phox and Tyr1472 expression. Anti-inflammatory cytokine (IL-10) and inflammatory cytokine secretion was determined using ELISA kits. The brain infarct volumes, TUNEL-positive neurons, expression of microglia, brain water content, blood-brain barrier structure damage, and gp91phox and Tyr1472 expression were increased, the Garcia neurological scores were significantly decreased in the IR group, and 2BFI relieved these alterations. The IL-10 concentration was increased in the IR group; 2BFI significantly improved this increase. The neuron apoptosis and necrosis rates, and production of reactive oxygen species (ROS) and inflammatory cytokines, including IL-6, IL-8, TNF-α, and 8-iso-PGF2α, were significantly increased by high glucose stimulation combined with oxygen-glucose deprivation treatment, which were inhibited by 2BFI. The 2BFI ameliorated cerebral ischemia-reperfusion injury in diabetes and decreased neuron death in an in vitro model. The mechanism underlying these findings may be related to the decreased production of inflammatory factors and reactive oxygen species from microglia.

This study synthesized an imidazoline biosurfactant (IM-BioSurf) from biomass residue and tetraethylenepentamine in two steps. Its structure was characterized by Fourier transform infrared spectros...

The Gemini imidazoline surfactants were synthesized from a series of saturated fatty acids. Electrochemical impedance spectroscopy (EIS), polarization curve, and quantum chemistry methods were used to study the corrosion inhibition behavior of Gemini imidazoline surfactants for X70 carbon steel in NaCl solution. Results reveal that such kind of surfactants has an outstanding inhibition effect on carbon steel X70 in NaCl solution and that the restrained efficiency of Gemini imidazoline in an alkaline solution is better than that in a neutral solution. The shorter the carbon chain length, the higher the suppressive efficiency. The higher the concentration of Gemini imidazoline surfactant, the better the inhibition effect.

A series of 6-amidinobenzothiazoles, linked via phenoxymethylene or directly to the 1,2,3-triazole ring with a p-substituted phenyl or benzyl moiety, were synthesised and evaluated in vitro against four human tumour cell lines and the protozoan parasite Trypanosoma brucei. The influence of the type of amidino substituent and phenoxymethylene linker on antiproliferative and antitrypanosomal activities was observed, showing that the imidazoline moiety had a major impact on both activities. Benzothiazole imidazoline 14a, which was directly connected to N-1-phenyl-1,2,3-triazole, had the most potent growth-inhibitory effect (IC50 = 0.25 µM) on colorectal adenocarcinoma (SW620), while benzothiazole imidazoline 11b, containing a phenoxymethylene linker, exhibited the best antitrypanosomal potency (IC90 = 0.12 µM). DNA binding assays showed a non-covalent interaction of 6-amidinobenzothiazole ligands, indicating both minor groove binding and intercalation modes of DNA interaction. Our findings encourage further development of novel structurally related 6-amidino-2-arylbenzothiazoles to obtain more selective anticancer and anti-HAT agents., Graphical Abstract

Di(het)areno-fused 1,4,7-(oxa)thiadiazecanes were synthesized by the reduction of the corresponding ten-membered lactams obtained, in turn, via the ‘hydrated imidazoline ring expansion’ (HIRE) methodology. Two of them displayed micromolar agonistic activity towards trace amine-associated receptor 1 (TAAR1) and no affinity towards a panel of dopamine (D2) and serotonin (5-HT1A, 5-HT2A and 5-HT7) receptors. These findings validate compounds of this chemotype as scaffolds for the design of selective aminergic receptor modulators.

Brain aging and dementia are current problems that must be solved. The levels of imidazoline 2 receptors (I(2)-IRs) are increased in the brain in Alzheimer’s disease (AD) and other neurodegenerative diseases. We tested the action of the specific and selective I(2)-IR ligand B06 in a mouse model of accelerated aging and AD, the senescence-accelerated mouse prone 8 (SAMP8) model. Oral administration of B06 for 4 weeks improved SAMP8 mouse behavior and cognition and reduced AD hallmarks, oxidative stress, and apoptotic and neuroinflammation markers. Likewise, B06 regulated glial excitatory amino acid transporter 2 and N-methyl-d aspartate 2A and 2B receptor subunit protein levels. Calcineurin (CaN) is a phosphatase that controls the phosphorylation levels of cAMP response element-binding (CREB), apoptotic mediator BCL-2-associated agonist of cell death (BAD) and GSK3β, among other molecules. Interestingly, B06 was able to reduce the levels of the CaN active form (CaN A). Likewise, CREB phosphorylation, BAD gene expression, and other factors were modified after B06 treatment. Moreover, phosphorylation of a target of CaN, nuclear factor of activated T-cells, cytoplasmic 1 (NFAT(C1)), was increased in B06-treated mice, impeding the transcription of genes related to neuroinflammation and neural plasticity. In summary, this I(2) imidazoline ligand can exert its beneficial effects on age-related conditions by modulating CaN pathway action and affecting several molecular pathways, playing a neuroprotective role in SAMP8 mice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11357-020-00281-2) contains supplementary material, which is available to authorized users.

A Bronsted basicity scale (∼24 pK units) for 85 commonly seen imidazole-, imidazoline-, triazole-, and thiazole-based N-heterocyclic olefins (NHOs) in DMSO was established using a well-examined com...

The mass loss method, electrochemical tests, scanning electron microscopy morphology analysis, and molecular dynamics simulation were used to study the synergistic mechanism of imidazoline (IM) and thiourea (TU) on ASTM A106B steel in CO2-saturated NaCl solution. The experimental results clearly revealed that IM and TU had good synergistic corrosion inhibition effect, and the combination of 5 mg/L IM and 5 mg/L TU exhibited the highest inhibition efficiency of 95.1%. Inhibitor molecules replaced the water molecules originally adsorbed on the metal surface and led to inhibition effects. The adsorption of the inhibitor mixtures had a better inhibition effect than individual inhibitors. The adsorption configuration and inhibition performance of the inhibitors demonstrated that the TU molecules first adsorbed on the metal surface to form the first layer, and then the IM adsorbed on TU to form the second layer. The number of water molecules originally adsorbed on the Fe surface decreased, and the diffusion of water molecules in the inhibitor film slowed down, thereby having a synergistic inhibition effect on metal corrosion.

While the alteration of I2 receptors has been associated with neurodegenerative and psychiatric disorders, among other brain dysfunctions, I2 selective agonists are also capable of inducing analgesia in models of chronic pain, improving cognition and inducing hypothermia and neuroprotection. However, the literature evaluating the antidepressant-like potential of I2 ligands is scarce and showed mixed results, whereas some studies reported antidepressant-like effects for certain I2 ligands others denied them. In this context, we evaluated the antidepressant-like potential of a highly selective I2-receptor ligand, LSL 60101 ([2-(2-benzofuranyl)-2-imidazole]). LSL 60101 was administered in adult male Sprague–Dawley rats daily during 16 days (doses of 10 and 20 mg/kg, ip) and its antidepressant-like potential was assessed through the course of treatment in the forced-swim test, novelty-suppressed feeding test and two-bottle choice test (sucrose preference). The regulation of several key neuroplasticity markers (i.e., FADD, p-ERK1/2, ERK1/2, p-JNK1/2, JNK1/2, mBDNF) was evaluated 24-h post-treatment by western blot analysis in the right hippocampus and the proliferation of neural progenitors was quantified in the left hippocampus by immunohistochemistry. The results showed that LSL 60101 did not induce an antidepressant-like effect over the course of treatment in any of the behavioral tests conducted, and it did not alter any of the hippocampal neuroplasticity markers evaluated. These results add to the existing literature by suggesting that not all I2 ligands might be capable of displaying an antidepressant-like potential, and that particularities in the chemical structure of each compound might help explain these discrepancies and deserve future studies.

Extensive clinical and experimental studies established that depression and mood disorders are highly prevalent neuropsychiatric conditions in Alzheimer’s disease (AD). However, its neurochemical basis is not clearly understood. Thus, understanding the neural mechanisms involved in mediating the co-morbidity of depression and AD may be crucial in exploring new pharmacological treatments for this condition. The present study investigated the role of the agmatinergic system in β-amyloid (Aββ1−42) peptide-induced depression using forced swim test (FST) in mice. Following the 28th days of its administration, Aβ1−42 peptide produced depression-like behavior in mice as evidenced by increased immobility time in FST and increased expression of pro-inflammatory cytokines like IL-6 and TNF-α compared to the control animals. The Aβ1−42 peptide-induced depression and neuroinflammatory markers were significantly inhibited by agmatine −, moxonidine, 2-BFI and l -arginine by once-daily administration during day 8–27 of the protocol. The antidepressant-like effect of agmatine in Aβ1−42 peptide in mice was potentiated by imidazoline receptor I1 agonist, moxonidine and imidazoline receptor I2 agonist 2-BFI at their sub-effective doses. On the other hand, it was completely blocked by imidazoline receptor I1 antagonist, efaroxan and imidazoline receptor I2 antagonist, idazoxan Also, agmatine levels were significantly reduced in brain samples of β-amyloid injected mice as compared to the control animals. In conclusion, the present study suggests the importance of endogenous agmatinergic system and imidazoline receptors system in β-amyloid induced a depressive-like behavior in mice. The data projects agmatine as a potential therapeutic target for the AD-associated depression and comorbidities.

Anti-cancer therapy based on the repeated administration of oxaliplatin is limited by the development of a disabling neuropathic syndrome with detrimental effects on the patient’s quality of life. The lack of effective pharmacological approaches calls for the identification of innovative therapeutic strategies based on new targets. We focused our attention on the imidazoline I(1) receptor (I(1)-R) and in particular on the selective I(1)-R agonist 2-(1-([1,1′-biphenyl]-2-yl)propan-2-yl)-4,5-dihydro-1H-imidazole) (carbophenyline). The purpose of this work was the preclinical evaluation of the efficacy of carbophenyline on oxaliplatin-induced neuropathic pain in mice. Carbophenyline, acutely per os administered (0.1–10 mg kg(−1)), induced a dose-dependent anti-hyperalgesic effect that was completely blocked by the pre-treatment with the I(1)-R antagonist 3 or the I(1)/α(2) receptor antagonist efaroxan, confirming the I(1)-R-dependent mechanism. Conversely, pre-treatment with the I(2)-R antagonist BU224 did not block the anti-nociceptive effect evoked by carbophenyline. Repeated oral administrations of carbophenyline (1 mg kg(−1)) for 14 days, starting from the first day of oxaliplatin injection, counteracted the development of neuropathic pain in all behavioral tests (cold plate, Von Frey, and paw pressure tests) carried out 24 h after the last carbophenyline treatment on days 7 and 14. In the dorsal horn of the spinal cord, carbophenyline significantly decreased the oxaliplatin-induced astrocyte activation detected by immunofluorescence staining by the specific labelling with GFAP antibody. In conclusion, carbophenyline showed anti-neuropathic properties both after acute and chronic treatment with preventive effect against oxaliplatin-induced astrocyte activation in the spinal cord. Therefore, I(1)-R agonists emerge as a new class of candidates for the management of oxaliplatin-induced neuropathic pain. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00873-y) contains supplementary material, which is available to authorized users.

The corrosion inhibition effects of the 2-undecyl-N-carboxymethyl-N-hydroxyethyl imidazoline on simple steels were indagated in 8 wt.% NH2SO3H media using loss of weight and electrochemical methods in conjunction with adsorption and DFT researches. The anti-corrosion effect of UHCI acquired from EIS study is great and the maximum anti-corrosion efficiency could reach 90.15%. The sorption of UHCI on simple steel conforms to the Langmuir sorption equation. The DFT studies reveal that UHCI is firmly chemisorbed upon the simple steel by the Fe…O σ-type dative bonds and isolates the contact between simple steel and NH2SO3H, thus protecting simple steel from the corrosion of NH2SO3H.

Imidazoline derivatives with different exocyclic substituents were simply prepared from common starting materials. The procedures were carried out in an eco-friendly manner. The antioxidant activity of these derivatives was explored by different experimental assays, such as ABTS.+ and DPPH. scavenging assay, as well as reducing power assay. The structural differences are discussed in terms of the results. Sulfur analogs showed higher antioxidant activity than their oxygenated counterparts. The same tendency was observed in microbiological studies, in which the same imidazoline compounds were assayed for light-mediated activity against of Staphylococcus aureus and Escherichia coli strains. A light-enhanced activity was observed for almost all the sulfated imidazolines after exposure to UV-A (400-320 nm) light. Fil: Faillace, Martín Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: Silva, Ana Paula. Universidade Federal do Piaui; Brasil Fil: Alves Borges Leal, Antonio Linkoln. Universidade Federal do Piaui; Brasil Fil: Muratori da Costa, Luciana. Universidade Federal do Piaui; Brasil Fil: Barreto, Humberto Medeiros. Universidade Federal do Piaui; Brasil Fil: Peláez, Walter José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina

An effective method for the synthesis of polysubstituted 2-imidazoline derivatives via palladium-catalyzed cyclization of 2,3-allenyl amines with aryl iodides is described. This pure domino process allows the formation of new carbon–carbon and carbon–nitrogen bonds in a single synthetic operation.

Objectives The knowledge that agmatine is found in the human body has existed for several years; however, its role in sepsis has not yet been studied. In the present study, we investigate the role of agmatine in the progression and treatment of sepsis. Design Clinical/laboratory investigations. Setting Medical centers/University-based research laboratory. Subjects Elective ICU patients with severe sepsis and healthy volunteers; C57BL/6 mice weighing 18-22 g. Interventions Serum agmatine level and its associations with inflammatory markers were assessed in patients with sepsis. Agmatine was administered intraperitoneally to mice before a lipopolysaccharide challenge. Human peripheral blood mononuclear cells and murine macrophages were pretreated with agmatine followed by lipopolysaccharide stimulation. Measurements and main results Serum agmatine levels were significantly decreased in patients with sepsis and lipopolysaccharide-induced mice, and correlated with Acute Physiology and Chronic Health Evaluation II score, procalcitonin, tumor necrosis factor-α, and interleukin-6 levels. In a therapeutic experiment, exogenous agmatine attenuated the cytokine production of peripheral blood mononuclear cells from patients with sepsis and healthy controls. Agmatine also exerted a significant beneficial effect in the inflammatory response and organ damage and reduced the death rate in lipopolysaccharide-induced mice. Imidazoline I2 receptor agonist 2-benzofuran-2-yl blocked the pharmacological action of agmatine; whereas, other imidazoline receptor ligands did not. Furthermore, agmatine significantly impaired the inflammatory response by inactivating nuclear factor-κB, but not protein 38 mitogen-activated protein kinase, c-Jun N-terminal kinase, extracellular signal-regulated kinase, and inducible nitric oxide synthase signaling in macrophages. Activation of imidazoline I2 receptor or knockdown of ribosomal S6 kinase 2 counteracted the effects of agmatine on phosphorylation and degradation of inhibitor of nuclear factor-κBα. Conclusions Endogenous agmatine metabolism correlated with the progression of sepsis. Supplemental exogenous agmatine could ameliorate the lipopolysaccharide-induced systemic inflammatory responses and multiple organ injuries through the imidazoline I2 receptor-ribosomal S6 kinase 2-nuclear factor-κB pathway. Agmatine could be used as both a clinical biomarker and a promising pharmaconutrient in patients with severe sepsis.

The Carbonic Anhydrase (CA, EC 4.2.1.1) activating properties of histamine have been known for a long time. This compound has been extensively modified but only in few instances the imidazole ring has been replaced with other heterocycles. It was envisaged that the imidazoline ring could be a bioisoster of the imidazole moiety. Indeed, we report that clonidine, a 2-aminoimidazoline derivative, was found able to activate several human CA isoforms (hCA I, IV, VA, VII, IX, XII and XIII), with potency in the micromolar range, while it was inactive on hCA II. A series of 2-aminoimidazoline, structurally related to clonidine, was then synthesised and tested on selected hCA isoforms. The compounds were inactive on hCA II while displayed activating properties on hCA I, VA, VII and XIII, with KA values in the micromolar range. Two compounds (10 and 11) showed some preference for the hCA VA or VII isoforms.

Imidazoline receptors historically referred to a family of nonadrenergic binding sites that recognize compounds with an imidazoline moiety, although this has proven to be an oversimplification. For example, none of the proposed endogenous ligands for imidazoline receptors contain an imidazoline moiety but they are diverse in their chemical structure. Three receptor subtypes (I1, I2, and I3) have been proposed and the understanding of each has seen differing progress over the decades. I1 receptors partially mediate the central hypotensive effects of clonidine-like drugs. Moxonidine and rilmenidine have better therapeutic profiles (fewer side effects) than clonidine as antihypertensive drugs, thought to be due to their higher I1/α2-adrenoceptor selectivity. Newer I1 receptor agonists such as LNP599 [3-chloro-2-methyl-phenyl)-(4-methyl-4,5-dihydro-3H-pyrrol-2-yl)-amine hydrochloride] have little to no activity on α2-adrenoceptors and demonstrate promising therapeutic potential for hypertension and metabolic syndrome. I2 receptors associate with several distinct proteins, but the identities of these proteins remain elusive. I2 receptor agonists have demonstrated various centrally mediated effects including antinociception and neuroprotection. A new I2 receptor agonist, CR4056 [2-phenyl-6-(1H-imidazol-1yl) quinazoline], demonstrated clear analgesic activity in a recently completed phase II clinical trial and holds great promise as a novel I2 receptor–based first-in-class nonopioid analgesic. The understanding of I3 receptors is relatively limited. Existing data suggest that I3 receptors may represent a binding site at the Kir6.2-subtype ATP-sensitive potassium channels in pancreatic β-cells and may be involved in insulin secretion. Despite the elusive nature of their molecular identities, recent progress on drug discovery targeting imidazoline receptors (I1 and I2) demonstrates the exciting potential of these compounds to elicit neuroprotection and to treat various disorders such as hypertension, metabolic syndrome, and chronic pain.

The environmental considerations need to be taken into account in any road resurfacing and upgrading project, for example, by reusing asphalt rubble for production of new pavement courses. Mixtures containing larger amounts of recycled asphalt pavement are improved by adding rejuvenator additives. The tests performed on the recycled asphalt mixtures containing lard imidazoline confirm the suitability of this agent for paving applications. Lard imidazoline was found to improve the stiffness modulus, fatigue performance and resistance to the action of water and freezing temperatures. The parameters obtained at the optimum content of additive complied with the criteria defined for virgin asphalt concrete and other mixtures of that kind.

Imidazoline derivatives with 7 levels of HOMO energy and imidazoline quaternary ammonium salts with 4 different LUMO energy levels were designed by adjusting the hydrophilic and hydrophobic groups of the imidazoline molecule. The changes in adsorption bonding and electron transfer of the imidazoline molecule on the metal surface were calculated by the density functional based tight binding method (DFTB+). It was found that when the HOMO and LUMO energy levels matched the iron Fermi level more closely, the imidazoline molecule could undergo more electron transfer with the iron substrate, thereby forming a stronger adsorption bond with the matrix. The corrosion inhibition performance of the imidazoline groups was further tested by electrochemical impedance spectroscopy (EIS) and scanning electron microscope (SEM). Finally, a clear correspondence between the frontier orbital energy level of the imidazoline molecule and its corrosion inhibition performance was discussed, which could provide an effective solution for designing high performance corrosion inhibitor molecules.

Microwave synthesis of imidazolines has been proven to have various advantages over conventional thermal methods in terms of reaction duration, better yield and sustainability. Multi-exploitability of imidazolines at industrial level is globally known. Moreover, claims of multi-fold improvement of the properties of gemini surfactants over their conventional monomeric counterparts challenge the researchers to synthesize gemini imidazoline surfactants using green synthetic routes. Cost-effective products provide an additional demand to commercialize the product easily. This research involves the microwave synthesis of gemini imidazolines using easily available, low-cost reactants. Synthesized products were characterized using standard characterization procedures and were evaluated for their surface-active properties and applications.

Caloric restriction increases lifespan across species and has health benefits in humans. Because complying with a low-calorie diet is challenging, here we investigated pharmacological interventions mimicking the benefits of caloric restriction. Searching for compounds that elicit a similar gene expression signature to caloric restriction, we identified rilmenidine, an I1-imidazoline receptor agonist and prescription medication for the treatment of hypertension. We then show that treating C. elegans with rilmenidine at young and older ages increases lifespan. We also demonstrate that the stress-resilience, healthspan, and lifespan benefits upon rilmenidine treatment in worms are mediated by the I1-imidazoline receptor nish-1, implicating this receptor as a potential longevity target. Furthermore, we show that rilmenidine treatment increased ERK phosphorylation via NISH-1. Consistent with the shared caloric-restriction-mimicking gene signature, supplementing rilmenidine to caloric restricted C. elegans, genetic reduction of TORC1 function, or rapamycin treatment did not further increase lifespan. The rilmenidine-induced longevity required the transcription factors FOXO/DAF-16 and NRF1,2,3/SKN-1, both important for caloric restriction-mediated longevity. Furthermore, we find that autophagy, but not AMPK signaling, was needed for rilmenidine-induced longevity. Lastly, we find that treating mice with rilmenidine showed transcriptional changes in liver and kidney similar to caloric restriction. Overall, our findings reveal rilmenidine as a caloric restriction mimetic and as a novel geroprotective compound.