38552-39-5Relevant academic research and scientific papers
Synthesis and (fluoro)solvatochromism of two 3-styryl-2-pyrazoline derivatives bearing benzoic acid moiety: A spectral, crystallographic and computational study
Matiadis, Dimitris,Nowak, Katarzyna E.,Alexandratou, Eleni,Hatzidimitriou, Antonios,Sagnou, Marina,Papadakis, Raffaello
, (2021)
In this work we report the synthesis of two fluorescent 2-pyrazoline derivatives exhibiting remarkable (fluoro)solvatochromic behavior. The pyrazolines were synthesized in one step from the corresponding monocarbonyl curcuminoids and 4-hydrazinobenzoic acid in high yield and purity and were fully characterized by means of NMR and FT-IR spectroscopy and HRMS spectrometry. The structure of the novel derivative 2 was also characterized by means of X-ray crystallography. Both compounds were studied computationally in the gas phase. Additionally, the effects of solvent polarity on the absorption and fluorescence spectra of these derivatives were investigated in a solvent group consisting of various neat molecular solvents exhibiting hydrogen bond donating (HBD), hydrogen bond accepting (HBA), and/or dipolar behavior. The solvent effects observed were quantified and rationalized by employing suitable multiparametric Linear Solvation Energy Relationships (LSERs) involving dipolarity, HBD-acidity and HBA-basicity terms. The contribution of each of these parameters provided insights on the predominant solute-solvent interactions occurring in solution. Importantly, some differences in the (fluoro)solvatochromic aptitude/behavior were revealed among the derivatives and they were rationalized on the basis of their structural diversity.
Electrospray ionization tandem mass spectrometry of monoketone curcuminoids
Vieira, Tatiana M.,Orenha, Renato P.,Crevelin, Eduardo J.,Furtado, Saulo S.P.,Vessecchi, Ricardo,Parreira, Renato L.T.,Crotti, Ant?nio E.M.
, (2020/02/18)
Rationale: Although monoketone curcuminoids (MKCs) have been largely investigated due to their biological activities, data on the gas-phase fragmentation reactions of protonated MKCs under collision-induced dissociation (CID) conditions are still scarce. Here, we combined electrospray ionization tandem mass spectrometry (ESI-MS/MS) data, multiple-stage mass spectrometry (MSn), deuterium exchange experiments, accurate-mass data, and thermochemical data estimated by computational chemistry to elucidate and to rationalize the fragmentation pathways of eleven synthetic MKCs. Methods: The MKCs were synthesized by Claisen-Schmidt condensation under basic (1–9) or acidic (10–11) conditions. ESI-CID-MS/MS analyses and deuterium-exchange experiments were carried out on a triple quadrupole mass spectrometer. MSn analyses on an ion trap mass spectrometer helped to elucidate the fragmentation pathways. Accurate-mass data and thermochemical data, obtained at the B3LYP/6–31+G(d,p) level of theory, were used to support the ion structures. Results: The most intense product ions were the benzyl ions ([C7H2R1R2R3R4R5]+) and the acylium ions ([M + H ? C8H3R1R2R3R4R5]+), which originated directly from the precursor ion as a result of two competitive hydrogen rearrangements. Product ions [M + H – H2O]+ and [M + H ? C6HR1R2R3R4R5]+, which are formed after Nazarov cyclization, were also common to all the analyzed compounds. In addition, ?Br and ?Cl eliminations were diagnostic for the presence of these halogen atoms at the aromatic ring, whereas ?CH3 eliminations were useful to identify the methyl and methoxy groups attached to this same ring. Nazarov cyclization in the gas phase occurred for all the investigated MKCs and did not depend on the presence of the hydroxyl group at the aromatic ring. However, the presence and the position of a hydroxyl group at the aromatic rings played a key role in the Nazarov cyclization mechanism. Conclusions: Our results reinforce some aspects of the fragmentation pathways previously published for 1,5-bis-(2-methoxyphenyl)-1,4-pentadien-3-one and 1,5-bis-(2-hydroxyphenyl)-1,4-pentadien-3-one. The alternative fragmentation mechanism proposed herein can explain the fragmentation of a wider diversity of monoketone curcuminoids.
Synthesis of tetracyclic oxindoles and evaluation of their α-glucosidase inhibitory and glucose consumption-promoting activity
Dodd, Robert H.,Hao, Lei,Ma, Ying,Ma, Yujiao,Sun, Hua,Yu, Peng,Zhang, Xinying,Zhang, Yinan,Zhao, Lianbo
supporting information, (2020/05/27)
A series of tetracyclic oxindole derivatives was synthesized by asymmetric 1, 3-dipole reaction in 2–4 steps in 57–86% overall yields. These compounds were evaluated for α-glucosidase inhibitory and glucose consumption-promoting activity in vitro. Compound 4l competitively and reversibly inhibited α-glucosidase (IC50 = 3.64 μM) with activity 14-fold higher than that of acarbose. Docking analysis substantiated these findings. In addition, compound 4l exhibited significant glucose consumption promoting activity at 1 μM.
New thiazolopyrimidine as anticancer agents: Synthesis, biological evaluation, DNA binding, molecular modeling and ADMET study
Al-Rashood, Sara T.,Elshahawy, Shymaa S.,El-Qaias, Asmaa M.,El-Behedy, Dina S.,Hassanin, Alshaimaa A.,El-Sayed, Selwan M.,El-Messery, Shahenda M.,Shaldam, Moataz A.,Hassan, Ghada S.
supporting information, (2020/10/23)
In the present study, new series of thiazolopyrimidine derivatives was synthesized as purine analogs. The structures of the products were confirmed through spectroscopic techniques such as NMR and mass spectrometry. In addition, the synthesized compounds
Structural optimization of natural product nordihydroguaretic acid to discover novel analogues as AcrB inhibitors
Alenzy, Rawaf,Liu, Xingbang,Ma, Shutao,Ma, Yingang,Mowla, Rumana,Polyak, Steven W.,Song, Di,Teng, Yuetai,Venter, Henrietta,Wang, Yinhu
, (2019/12/24)
Drug efflux pumps confer multidrug resistance to dangerous bacterial pathogens which makes these proteins promising drug targets. Herein, we present initial chemical optimization and structure-activity relationship (SAR) data around a previously described efflux pump inhibitor, nordihydroguaretic acid (NDGA). Four series of novel NDGA analogues that target Escherichia coli AcrB were designed, synthesized and evaluated for their ability to potentiate the activity of antibiotics, to inhibit AcrB-mediated substrate efflux and reduce off-target activity. Nine novel structures were identified that increased the efficacy of a panel of antibiotics, inhibited drug efflux and reduced permeabilization of the bacterial outer and inner membranes. Among them, WA7, WB11 and WD6 possessing broad-spectrum antimicrobial sensitization activity were identified as NDGA analogues with favorable properties as potential AcrB inhibitors, demonstrating moderate improvement in potency as compared to NDGA. In particular, WD6 was the most broadly active analogue improving the activity of all four classes of antibacterials tested.
Antimicrobial Activity of Monoketone Curcuminoids Against Cariogenic Bacteria
Vieira, Tatiana M.,dos Santos, Isabella A.,Silva, Thayná S.,Martins, Carlos H. G.,Crotti, Ant?nio E. M.
, (2018/08/01)
We evaluated the antimicrobial activity of 25 monoketone curcuminoids (MKCs) against a representative panel of cariogenic bacteria in terms of their minimum inhibitory concentration (MIC) values. Curcumin A (10) displayed promising activity against Streptococcus mutans (MIC?=?50?μg/ml) and Streptococcus mitis (MIC?=?50?μg/ml) as well as moderate activity against S.?sanguinis (MIC?=?100?μg/ml), Lactobacillus casei (MIC?=?100?μg/ml), and Streptococcus salivarius (MIC?=?200?μg/ml). Results indicated higher activity of compound 10 than that of its bis-β-diketone analog. Additionally, compounds 3a (1,5-bis(4-methylphenyl)pentan-3-one) and 7b (1,5-bis(4-bromophenyl)pentan-3-ol) were moderately active against S.?mitis (MIC?=?100?μg/ml) and S.?salivarus (MIC?=?200?μg/ml).
Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin
Deck, Lorraine M.,Hunsaker, Lucy A.,Vander Jagt, Thomas A.,Whalen, Lisa J.,Royer, Robert E.,Vander Jagt, David L.
, p. 854 - 865 (2017/12/13)
Inflammation and oxidative stress are common in many chronic diseases. Targeting signaling pathways that contribute to these conditions may have therapeutic potential. The transcription factor Nrf2 is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. Nrf2 is widespread in the CNS and is recognized as an important regulator of brain inflammation. The natural product curcumin exhibits numerous biological activities including ability to induce the expression of Nrf2-dependent phase II and anti-oxidant enzymes. Curcumin has been examined in a number of clinical studies with limited success, mainly owing to limited bioavailability and rapid metabolism. Enone analogues of curcumin were examined with an Nrf2 reporter assay to identify Nrf2 activators. Analogues were separated into groups with a 7-carbon dienone spacer, as found in curcumin; a 5-carbon enone spacer with and without a ring; and a 3-carbon enone spacer. Activators of Nrf2 were found in all three groups, many of which were more active than curcumin. Dose-response studies demonstrated that a range of substituents on the aromatic rings of these enones influenced not only the sensitivity to activation, reflected in EC50 values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2 by these analogues.
CURCUMIN DERIVATIVE
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Paragraph 0064; 0065, (2018/10/19)
PROBLEM TO BE SOLVED: To provide a new curcumin derivative. SOLUTION: A chemical compound is shown by formula (1) as follows. In the formula, R1 is a 1-5C alkyl group, a 2-5C alkenyl group or a 2-5C alkynyl group; R2 is a 1-5C alkyl group, a 2-5C alkenyl group or a 2-5C alkynyl group; n1 is an integral number of 1-4, and when n1 is 2 or more, R1 may be the same or different from each other; and n2 is an integral number of 1-4, and when n2 is 2 or more, R2 may be the same or different from each other. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2018,JPOandINPIT
Dihedral-Angle-Controlled Crossover from Static Hole Delocalization to Dynamic Hopping in Biaryl Cation Radicals
Talipov, Marat R.,Navale, Tushar S.,Hossain, Mohammad M.,Shukla, Ruchi,Ivanov, Maxim V.,Rathore, Rajendra
supporting information, p. 266 - 269 (2016/12/30)
In cases of coherent charge-transfer mechanism in biaryl compounds the rates follow a squared cosine trend with varying dihedral angle. Herein we demonstrate using a series of biaryl cation radicals with varying dihedral angles that the hole stabilization
Synthesis and synergistic antifungal effects of monoketone derivatives of curcumin against fluconazole-resistant Candida spp.
Zhao, Fei,Dong, Huai-Huai,Wang, Yuan-Hua,Wang, Tian-Yi,Yan, Ze-Hao,Yan, Fang,Zhang, Da-Zhi,Cao, Ying-Ying,Jin, Yong-Sheng
, p. 1093 - 1102 (2017/07/12)
Twenty-three monoketone derivatives of curcumin were synthesized to investigate the synergy with fluconazole against fluconazole-resistant Candida spp. The minimal inhibitory concentration (MIC80) and the fractional inhibitory concentration index (FICI) of the antifungal synergist fluconazole were measured against fluconazole-resistant C. albicans, C. tropicalis and C. krusei in vitro. Most of these compounds showed good synergistic activities against C. tropicalis. Among them, compound 9 exhibited significant synergistic activities against Candida spp. SARs were also discussed. In particular, a cell growth test exhibited that a combination of 1 μg ml-1 fluconazole and 64 μg ml-1 or 128 μg ml-1 compound 9 showed the most potent fungicidal effect against C. tropicalis. The synergistic effect may be associated with the changes of the intracellular ATP content and cell membrane permeability. Our results provided a basis for future evaluation and development of these compounds as leads for therapeutics for fluconazole-resistant candidiasis.
