A series of surfactants combining carbohydrate and imidazolium head groups were prepared and investigated on their assembly behavior. The presence of the imidazolium group dominated the interactions of the surfactants, leading to high CMCs and large molecular surface areas, reflected in curved rather than lamellar surfactant assemblies. The carbohydrate, on the other hand, stabilized molecular assemblies slightly and reduced the surface tension of surfactant solutions considerably. A comparative emulsion study discourages the use of pure alkyl imidazolium glycosides owing to reduced assembly stabilities compared with APGs. However, the surfactants are believed to have potential as component in carbohydrate based surfactant mixtures.
The formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was investigated using a kinetic study approach as described by first-order, Arrhenius, and Eyring equations. Chemical model systems with different amino acid precursors (proline, phenylalanine, and glycine) were examined at different times (4, 8, 12, and 16 min) and temperatures (150, 180, 210, 240, and 270 °C). PhIP was detected using high-performance liquid chromatography equipped with fluorescence detector (HPLC-FLD). The good fit in first-order suggested that PhIP formation was influenced by the types of amino acids and PhIP concentration significantly increased with time and temperature (up to 240 °C). PhIP was detected in proline and phenylalanine model systems but not in the glycine model system. The phenylalanine model system demonstrated low activation energy (Ea) of 95.36 kJ/mol that resulted in a high rate of PhIP formation (great amount of PhIP formed). Based on the ∆S‡ values both proline and phenylalanine demonstrated bimolecular rate-limiting steps for PhIP formation. Altogether these kinetic results could provide valuable information in predicting the PhIP formation pathway.
Several new substituted sulfonamide compounds were synthesized and their structures were confirmed by ¹H-NMR, ¹³C-NMR, FT-IR, and mass spectroscopy. The antibacterial activities of the synthesized compounds were screened against standard strains of six Gram positive and four Gram negative bacteria using the microbroth dilution assay. Most of the compounds studied showed promising activities against both types of bacteria.
Current study is based on the biology-oriented drug synthesis (BIODS) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives 1-26, by treating metronidazole with different aryl and hetero-aryl carboxylic acids in the presence of 1,1'-carbonyl diimidazole (CDI) as a coupling agent. Structures of all synthetic derivatives were confirmed with the help of various spectroscopic techniques such as EI-MS, (1)H -NMR and (13)C NMR. CHN elemental analyses were also found in agreement with the calculated values. Synthetic derivatives were evaluated to check their β-glucuronidase inhibitory activity which revealed that except few derivatives, all demonstrated good inhibition in the range of IC50 = 1.20 ± 0.01-60.30 ± 1.40 μM as compared to the standard d-saccharic acid 1,4-lactone (IC50 = 48.38 ± 1.05 μM). Compounds 1, 3, 4, 6, 9-19, and 21-24 were found to be potent analogs and showed superior activity than standard. Limited structure-activity relationship is suggested that the molecules having electron withdrawing groups like NO2, F, Cl, and Br, were displayed better activity than the compounds with electron donating groups such as Me, OMe and BuO. To verify these interpretations, in silico study was also performed, a good correlation was observed between bioactivities and docking studies.
A new library of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl ether derivatives (1-23) were synthesized and characterized by EI-MS and 1H NMR, and screened for their α-amylase inhibitory activity. Out of twenty-three derivatives, two molecules 19 (IC50=0.38±0.82µM) and 23 (IC50=1.66±0.14µM), showed excellent activity whereas the remaining compounds, except 10 and 17, showed good to moderate inhibition in the range of IC50=1.77-2.98µM when compared with the standard acarbose (IC50=1.66±0.1µM). A plausible structure-activity relationship has also been presented. In addition, in silico studies was carried out in order to rationalize the binding interaction of compounds with the active site of enzyme.
Imidazoles and phenylthiazoles are an important class of heterocycles that demonstrate a wide range of biological activities against various types of cancers, diabetes mellitus and pathogenic microorganisms. The heterocyclic structure having oxothiazolidine moiety is an important scaffold present in various drugs, with potential for enzyme inhibition. In an effort to discover new heterocyclic compounds, we synthesized 26 new 4,5-diphenyl-1H-imidazole, phenylthiazole, and oxothiazolidine heterocyclic analogues that demonstrated potent α-glucosidase inhibition and anticancer activities. Majority of the compounds noncompetitively inhibited α-glucosidase except for two that exhibited competitive inhibition of the enzyme. Docking results suggested that the noncompetitive inhibitors bind to an apparent allosteric site on the enzyme located in the vicinity of the active site. Additionally, the analogues also exhibited significant activity against various types of cancers including non-small lung cancer. Since tubulin protein plays an important role in the pathogenesis of non-small lung cancer, molecular docking with one of the target compounds provided important clues to its binding mode. The current work on imidazoles and phenylthiazole derivatives bears importance for designing of new antidiabetic and anticancer drugs.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with multiple factors associated with its pathogenesis. Our strategy against AD involves design of multi-targeted 2-substituted-4,5-diphenyl-1H-imidazole analogues which can interact and inhibit AChE, thereby, increasing the synaptic availability of ACh, inhibit BuChE, relieve induced oxidative stress and confer a neuroprotective role. Molecular docking was employed to study interactions within the AChE active site. In silico ADME study was performed to estimate pharmacokinetic parameters. Based on computational studies, some analogues were synthesized and subjected to pharmacological evaluation involving antioxidant activity, toxicity and memory model studies in animals followed by detailed mechanistic in vitro cholinesterase inhibition study. Amongst the series, analogue 13 and 20 are the most promising multi-targeted candidates which can potentially increase memory, decrease free radical levels and protect neurons against cognitive deficit.