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1.
Cobalt(III) Schiff base complexes have been used as potent inhibitors of protein function through the coordination to histidine residues essential for activity. The kinetics and thermodynamics of the binding mechanism of Co(acacen)(NH(3))(2)Cl [Co(acacen); where H(2)acacen?is?bis(acetylacetone)ethylenediimine] enzyme inhibition has been examined through the inactivation of matrix metalloproteinase?2 (MMP-2) protease activity. Co(acacen) is an irreversible inhibitor that exhibits time- and concentration-dependent inactivation of MMP-2. Co(acacen) inhibition of MMP-2 is temperature-dependent, with the inactivation increasing with temperature. Examination of the formation of the transition state for the MMP-2/Co(acacen) complex was determined to have a positive entropy component indicative of greater disorder in the MMP-2/Co(acacen) complex than in the reactants. With further insight into the mechanism of Co(acacen) complexes, Co(III) Schiff base complex protein inactivators can be designed to include features regulating activity and protein specificity. This approach is widely applicable to protein targets that have been identified to have clinical significance, including matrix metalloproteinases. The mechanistic information elucidated here further emphasizes the versatility and utility of Co(III) Schiff base complexes as customizable protein inhibitors. 相似文献
2.
An understanding of why adenine (A) pairs with thymine (T) and cytosine (C) with guanine (G) in DNA is very useful in the
design of sensors and other related devices. We report the use of dissociation energies, geometries and molecular electrostatic
potentials (MEPs) to justify the canonical (AT and CG) Watson-Crick pairs. We also analyze all mismatches in both configurations—cis
and trans—with respect to their glycoside bonds. As expected, we found that the most stable pair configuration corresponds
to CG, providing an energy criterion for that preferred configuration. The reason why A gets together with T is much more
difficult to explain as the energy of this pair is smaller than the energy of some other mismatched pairs. We tested MEPs
to see if they could shed light on this problem. Interestingly, MEPs yield a unique pattern (shape) for the two canonical
cases but different shapes for the mismatches. A tunnel of positive potential surrounded by a negative one is found interconnecting
the three H-bonds of CG and the two of AT. This MEP tunnel, assisted partially by energetics and geometrical criteria, unambiguously
determine a distinctive feature of the affinity between A and T as well as that between G and C. 相似文献
3.
Bo Fu Ryosuke Takeda Yupiao Zou Hiroyuki Konno Hiroki Moriwaki Hidenori Abe Jianlin Han Kunisuke Izawa Vadim A. Soloshonok 《Chirality》2020,32(12):1354-1360
Over last decade, the use of Ni(II) complexes, derived from of glycine Schiff bases with chiral tridentate ligands, has emerge as a leading methodology for preparation of structurally diverse Tailor-Made Amino Acids, the key structural units in modern medicinal chemistry, and drug design. Here, we report asymmetric synthesis of derivatives of (S)-α-(octyl)glycine ((S)-2-aminodecanoic acid) and its N-Fmoc derivative via alkylation of chiral nucleophilic glycine equivalent with n-octyl bromide. Under the optimized conditions, the alkylation proceeds with excellent yield (98.1%) and diastereoselectivity (98.8% de). The observed stereochemical outcome and convenient reaction conditions bode well for application of this method for large-scale asymmetric synthesis of (S)-2-aminodecanoic acid and its derivatives. 相似文献
4.
The kinetics of Schiff base formation between the cholesterol ozonolysis product 3β-hydroxy-5-oxo-5,6-secocholestan-6-al and dimyristoyl phosphatidylethanolamine was investigated. The activation energy of Schiff base formation at temperatures above and below the phase transition of the phospholipid was calculated. Increase in the activation energy derived from perturbation of the surface structure by the process of Schiff base formation was demonstrated. The presence of the Schiff base with the aldolization product of the oxysterol was also observed and its significance is discussed. 相似文献
5.
Vasudeva Rao Avupati Rajendra Prasad Yejella Venkateswara Rao Parala Kishore Naidu Killari Venkata Madhava Reddy Papasani Prasad Cheepurupalli Venkateswara Rao Gavalapu Bhavani Boddeda 《Bioorganic & medicinal chemistry letters》2013,23(21):5968-5970
A series of some novel 1,3,5-triazine–Schiff base conjugates (1–32) have been synthesized and evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv using Alamar Blue assay and the activity expressed as the minimum inhibitory concentration (MIC) in μg/mL. Compounds 4 (4-Methoxy-6-methyl-N-(3,4,5-trimethoxybenzylidene)-1,3,5-triazin-2-amine), 11 (4-Methoxy-6-methyl-N-(2-hydroxy-3-bromo-5-chloro-benzylidene)-1,3,5-triazin-2-amine) and 24 (4-Methoxy-6-methyl-N-(1-(2,5-dihydroxyphenyl)ethylidene)-1,3,5-triazin-2-amine) exhibited a significant activity at 3.125, 6.25 and 6.25 μg/mL, respectively, when compared with the antitubercular drugs such as ethambutol (3.125 μg/mL), pyrazinamide (6.25 μg/mL) and streptomycin (6.25 μg/mL) and it could be a potential starting point to develop new lead compounds in the fight against Mycobacterium tuberculosis H37Rv. 相似文献
6.
Electronic spectra and ground and excited state electronic structures of normal G and rare tautomeric G1z.sbnd;C1 base pairs as well as of the individual rare tautomeric bases (purines and pyrimidines) have been studied using the VE-PPP molecular orbital method. The nature and consequences of the lowest energy purine-localized and purine to pyrimidine charge transfer type π?π1 singlet excitations of the base pairs have been investigated. The results indicate that in these excited states, particularly in the charge transfer excited state, the probability for the GC base pair to change over to G1C1 would be larger than in the ground state. The likeliness of the relevance of results obtained experimentally by other workers from the study of a model system to the GC base pair is discussed. 相似文献
7.
Sowrirajan Chandrasekaran Natesan Sudha D. Premnath 《Journal of biomolecular structure & dynamics》2013,31(9):1945-1956
This work deals with the synthesis of 6-methyl-3-[(4′-methylphenyl)imino]methyl-4H-chromen-4-one (MMPIMC), its binding to β-cyclodextrin, and the influence of the cyclodextrin complexation on the compound’s binding to bovine serum albumin (BSA). The 1:2 stoichiometry for the complexation of MMPIMC with β-cyclodextrin is determined with the binding constant of 1.90 × 104 M?2. The structure of host–guest complex plays a role in protein binding of MMPIMC. One- and two-dimensional NMR spectra are used to determine the mode of binding of the guest to β-cyclodextrin cavity and the structure of the inclusion complex is proposed. The binding of MMPIMC with BSA in the absence and the presence of β-cyclodextrin is studied. The binding strengths of MMPIMC–BSA (1.73 × 105 M?1) and β-cyclodextrin-complexed MMPIMC–BSA (9.0 × 104 M?1) show difference in magnitude. The Förster Resonance Energy Transfer efficiency and the proximity of the donor and acceptor molecules, are modulated by β-cyclodextrin. Molecular modeling is used to optimize the sites and mode of binding of MMPIMC with bovine serum albumin. 相似文献
8.
Jigar A. Makawana Juan Sun Hai-Liang Zhu 《Bioorganic & medicinal chemistry letters》2013,23(23):6264-6268
New Schiff’s base derivatives 5a–5h have been synthesized by reaction between 1-(4-bromophenyl)-2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethanone 3 and various benzohydrazide 4a–4h in presence of nickel (II) nitrate as a catalyst in ethanol at room temperature in good yield (54–88%). All compounds were tested for antibacterial as well as anticancer and inhibition of EGFR. Of the compounds studied, compounds 5d, 5f and 5g in the case of antiproliferation and inhibition of EGFR as well as compounds 5b, 5c, 5e and 5h in the case of antibacterial activity were found to be most effective compounds in the series. Compound 5f shows effective inhibition (IC50 = 0.21 ± 0.02 μM) by binding in to the active pocket of EGFR receptor with minimum binding energy (ΔGb = ?49.4869 kcal/mol). 相似文献
9.
《Bioorganic & medicinal chemistry letters》2014,24(7):1734-1736
New Schiff’s base derivatives 5a–j have been synthesized by reaction between 2-phenoxyquinoline-3-carbaldehydes 3a–j and 2-(2-methyl-5-nitro-1H-imidazol-1-yl)acetohydrazide 4 in presence of nickel(II) nitrate as a catalyst in ethanol under reflux in good yield (78–92%). All compounds were tested for anticancer and inhibition of EGFR. Of the compounds studied, majority of the compounds showed effective antiproliferation and inhibition of EGFR and HER-2 activities. Compound 5h showed most effective inhibition (IC50 = 0.12 ± 0.05 μM) by binding in to the active pocket of EGFR receptor with minimum binding energy (ΔGb = −58.3691 kcal/mol). The binding was stabilized by two hydrogen bonds, two π–cation and one π–sigma interactions. Compound 5d showed most effective inhibition (IC50 = 0.37 ± 0.04 μM). 相似文献
10.
It has long been recognized that T·T mismatches can adopt two different modes of exchangeable wobble base pairs in which no preferential pairing mode has been observed. In this study, we have performed a systematic nuclear magnetic resonance (NMR) investigation to study the sequence context effect on the pairing modes of T·T mismatches. Our results reveal for the first time that preferential pairing mode does exist in T·T mismatches with specific type of flanking base pairs. 相似文献
11.
Ole K. Hansen Suchitra Changtragoon Bundit Ponoy Juan Lopez John Richard Erik D. Kjær 《Tree Genetics & Genomes》2017,13(4):87
Teak (Tectona grandis Linn. f.) is one of the major plantation timbers of the world. The species is native to India, Myanmar, Thailand and Laos in South East Asia but was translocated to several countries in Africa and Central and South America during the past century. Today, large areas of plantations are grown outside the species native range. It is speculated that genetic bottlenecks and founder effects combined with new selection pressures under new growing conditions have led to the formation of distinct landraces; this hypothesis is supported by results from international provenance tests. In the present study, we apply genetic markers to identify the likely origin of teak grown outside its native range and examine if the landraces show signs of reduced genetic diversity. We find large variation in the level of diversity among landraces, although not larger than that observed among native populations. We conclude that variation in the studied teak landraces probably reflects their areas of genetic origin rather than severe founder effects created during their introduction. The genetic data suggests that the studied landraces originated from either the semi-moist east coast of India, southern Myanmar or western Thailand. These results indicate that translocation of teak has mainly come from a certain part of the native distribution and that this did not include the widespread natural teak areas of southern, dry interior or western India or northern Myanmar. 相似文献
12.
Background
Dihydroartemisinin (DHA), a powerful anti-malarial drug, has been used as monotherapy and artemisinin-based combination therapy (ACT) for more than decades. So far, however, the tissue distribution and metabolic profile of DHA data are not available from animal and humans.Methods
Pharmacokinetics, tissue distribution, mass balance, and elimination of [14C] DHA have been studieded in rats following a single intravenous administration. Protein binding was performed with rat and human plasma. Drug concentrations were obtained up to 192 hr from measurements of total radioactivity and drug concentration to determine the contribution by the parent and metabolites to the total dose of drug injected from whole blood, plasma, urine and faecal samples.Results
Drug was widely distributed after 1 hr and rapidly declined at 24 hr in all tissues except spleen until 96 hrs. Only 0.81% of the total radioactivity was detected in rat brain tissue. DHA revealed a high binding capacity with both rat and human plasma proteins (76–82%). The concentration of total radioactivity in the plasma fraction was less than 25% of that in blood total. Metabolism of DHA was observed with high excretion via bile into intestines and approximately 89–95% dose of all conjugations were accounted for in blood, urine and faeces. However, the majority of elimination of [14C] DHA was through urinary excretion (52% dose). The mean terminal half-lives of plasma and blood radioactivity (75.57–122.13 h) were significantly prolonged compared with that of unchanged DHA (1.03 h).Conclusion
In rat brain, the total concentration of [14C] was 2-fold higher than that in plasma, indicating the radioactivity could easily penetrate the brain-blood barrier. Total radioactivity distributed in RBC was about three- to four-fold higher than that in plasma, suggesting that the powerful anti-malarial potency of DHA in the treatment of blood stage malaria may relate to the high RBC binding. Biliary excretion and multiple concentration peaks of DHA have been demonstrated with high urinary excretion due to a most likely drug re-absorption in the intestines (enterohepatic circulation). The long lasting metabolites of DHA (> 192 hr) in the rats may be also related to the enterohepatic circulation. 相似文献13.
Summary Stability of Schiff bases from Pyridoxal-5-phosphate and- and non-amino acids and amines have been studied in a wide range of pH. Furthermore the transamination process for the PLP-serine Schiff base and the cyclization reaction of PLP-histidine Schiff base have also been studied.Results show that the-position on carboxyl group of amino acids plays an important role on the mechanism of hydrolysis of imine bond. Absence of ionic groups in the surroundings of that bond seems to be an important fact of stability.In the transamination reaction, the rate-determining step is the isomerization of the Schiff base to ketoimine, since the rate constants for disappearance of Schiff base coincide with the rate constants for PMP formation. This process is catalyzed by the OH–/H2O system and the monoprotonated amino acid. 相似文献
14.
T4 RNA ligase 2 (Rnl2) repairs 3′-OH/5′-PO4 nicks in duplex nucleic acids in which the broken 3′-OH strand is RNA. Ligation entails three chemical steps: reaction of Rnl2 with ATP to form a covalent Rnl2–(lysyl-Nζ)–AMP intermediate (step 1); transfer of AMP to the 5′-PO4 of the nick to form an activated AppN– intermediate (step 2); and attack by the nick 3′-OH on the AppN– strand to form a 3′–5′ phosphodiester (step 3). Here we used rapid mix-quench methods to analyze the kinetic mechanism and fidelity of single-turnover nick sealing by Rnl2–AMP. For substrates with correctly base-paired 3′-OH nick termini, kstep2 was fast (9.5 to 17.9 sec−1) and similar in magnitude to kstep3 (7.9 to 32 sec−1). Rnl2 fidelity was enforced mainly at the level of step 2 catalysis, whereby 3′-OH base mispairs and oxoguanine, oxoadenine, or abasic lesions opposite the nick 3′-OH elicited severe decrements in the rate of 5′-adenylylation and relatively modest slowing of the rate of phosphodiester synthesis. The exception was the noncanonical A:oxoG base pair, which Rnl2 accepted as a correctly paired end for rapid sealing. These results underscore (1) how Rnl2 requires proper positioning of the 3′-terminal ribonucleoside at the nick for optimal 5′-adenylylation and (2) the potential for nick-sealing ligases to embed mutations during the repair of oxidative damage. 相似文献
15.
Apurba Biswas Michael G.B. Drew Joan Ribas Carmen Diaz Ashutosh Ghosh 《Inorganica chimica acta》2011,379(1):28
Two phenoxido bridged dinuclear Cu(II) complexes, [Cu2(L1)2(NCNCN)2] (1) and [Cu2(L2)2(NCNCN)2]·2H2O (2) have been synthesized using the tridentate reduced Schiff-base ligands 2-[1-(2-dimethylamino-ethylamino)-ethyl]-phenol (HL1) and 2-[1-(3-methylamino-propylamino)-ethyl]-phenol (HL2), respectively. The complexes have been characterized by X-ray structural analyses and variable-temperature magnetic susceptibility measurements. Both the complexes present a diphenoxido bridging Cu2O2 core. The geometries around metal atoms are intermediate between trigonal bipyramid and square pyramid with the Addison parameters (τ) = 0.57 and 0.49 for 1 and 2, respectively. Within the core the Cu–O–Cu angles are 99.15° and 103.51° and average Cu–O bond distances are 2.036 and 1.978 Å for compounds 1 and 2, respectively. These differences have marked effect on the magnetic properties of two compounds. Although both are antiferromagnetically coupled, the coupling constants (J = −184.3 and −478.4 cm−1 for 1 and 2, respectively) differ appreciably. 相似文献
16.
Shigeru Tanaka Ke Cao Atsuko Niimi Siripan Limsirichaikul Huang Qin Miao Noriko Nakamura Takashi Murate Yoshinori Hasegawa Takashi Takahashi Motoshi Suzuki 《DNA Repair》2010,9(5):534-541
Recent studies have revealed that the base selection step of DNA polymerases (pol) plays a role in prevention of DNA replication errors. We investigated whether base selection is required for the DNA replication fidelity of pol α and genomic stability in human cells. We introduced an Leu864 to Phe substitution (L864F) into human pol α and performed an in vitro LacZα forward mutation assay. Our results showed that the overall mutation rate was increased by 180-fold as compared to that of the wild-type. Furthermore, steady state kinetics analyses consistently showed that L864F pol α had a decreased discrimination ability between correct and incorrect nucleotide incorporation, as well as between matched and mismatched primer termini. L864F pol α also exhibited increased translesion activity over the abasic, etheno-A, O4-methyl-T, and O6-methyl-G sites. In addition, our steady state kinetics analyses supported the finding of increased translesion activity of L864F pol α over O6-methyl-G. We also established stable clones transfected with pola1L864F utilizing the human cancer cell line HCT116. Using the HPRT gene as a reporter, the spontaneous mutation rate of pola1L864F cells was determined to be 2.4-fold greater than that of wild-type cells. Mutation assays were also carried out using cells transiently transfected with the wild-type or pola1L864F, and increased mutant frequencies were observed in pola1L864F cells under both spontaneous and methyl methanesulfonate-induced conditions. Together, our results indicate that the base selection step in human pol α functions to prevent DNA replication errors and maintain genomic integrity in HCT116 cells. 相似文献
17.
Aim
Female cardiac transplant recipients' aerobic capacity is 60% lower than sex and age-predicted values. The effect of exercise training on restoring the impaired aerobic endurance and muscle strength in female cardiac transplant recipients is not known. This study examined the effect that aerobic and strength training have on improving aerobic endurance and muscle strength in female cardiac transplant recipients.Methods
20 female cardiac transplant recipients (51 ± 11 years) participated in this investigation. The subjects performed a baseline six-minute walk test and a leg-press strength test when they were discharged following cardiac transplantation. The subjects then participated in a 12-week exercise program consisting of aerobic and lower extremity strength training. Baseline assessments were repeated following completion of the exercise intervention.Results
At baseline, the cardiac transplant recipients' aerobic endurance was 50% lower than age-matched predicted values. The training program resulted in a significant increase in aerobic endurance (pre-training: 322 ± 104 m vs. post-training: 501 ± 99 m, p < 0.05) and leg-press strength (pre-training: 48 ± 16 kg. vs. post-training: 78 ± 27 kg, p < 0.05).Conclusion
Aerobic and strength training are effective interventions that can partially restore the impaired aerobic endurance and strength found in female cardiac transplant recipients. 相似文献18.
Four trinuclear Cu(II) complexes, [(CuL1)3(μ3-OH)](NO3)2 (1), [(CuL2)3(μ3-OH)](I)2·H2O (2), [(CuL3)3(μ3-OH)](I)2 (3) and [(CuL1)3(μ3-OH)][CuII3] (4), where HL1 (8-amino-4-methyl-5-azaoct-3-en-2-one), HL2 [7-amino-4-methyl-5-azaoct-3-en-2-one] and HL3 [7-amino-4-methyl-5-azahept-3-en-2-one] are the three tridentate Schiff bases, have been synthesized and structurally characterized by X-ray crystallography. All four complexes contain a partial cubane core, [(CuL)3(μ3-OH)]2+ in which the three [CuL] subunits are interconnected through two types of oxygen bridges afforded by the oxygen atoms of the ligands and the central OH− group. The copper(II) ions are in a distorted square-pyramidal environment. The equatorial plane consists of the bridging oxygen of the central OH− group together with three atoms (N, N, O) from the Schiff base. The oxygen atom of the Schiff base also coordinates to the axial position of Cu(II) of another subunit to form the cyclic trimer. Magnetic susceptibilities have been determined for these complexes over the temperature range of 2-300 K. The isotropic Hamiltonian, H = −J12S1S2 − J13S1S3 − J23S2S3 has been used to interpret the magnetic data. The best fit parameters obtained are: J = −54.98 cm−1, g = 2.24 for 1; J = −56.66 cm−1, g = 2.19 for 2;J = −44.39 cm−1, g = 2.16 for 3; J = −89.92 cm−1, g = 2.25 for 4. The EPR data at low temperature indicate that the phenomenon of spin frustration occurs for complexes 1-3. 相似文献
19.
We describe the enantioseparation of functionalized derivatives of the Tr?ger base by HPLC on commercially available chiral stationary phases. Cellulose-derived Chiralcel OJ and brush-type Whelk O1 are demonstrated to be complementary to each other in their scope. On the basis of the results obtained, the separation of selected compounds was successfully transferred onto semipreparative columns. We believe that the availability of enantiopure functionalized derivatives of the Tr?ger base will stimulate the further use of this interesting molecular scaffold in molecular recognition, asymmetric catalysis, and related areas of research and technology. 相似文献
20.
A novel chiral Schiff base containing α-d-altropyranoside unit, methyl 4,6-O-benzylidene-3-deoxy-3-(2-salicylideneaminoethylamino)-α-d-altropyranoside (3, Me-Alt-NNOH), has been prepared. Treatment of zinc chloride with 3 in the presence of triethylamine afforded a five-coordinated zinc(II) complex [Zn(Me-Alt-NNO)Cl] (4). Both 3 and 4 have been characterized by infrared, 1H NMR, 13C NMR, MS, and elemental analysis. The crystal structure of 4 has been determined by X-ray diffraction. Crystal structure analysis shows that the complex 4 exits a distorted triangular bipyramid geometry and the Schiff base motif acts as a uninegatively charged tetradentate chelating agent. The methoxy and amino groups cis-chelate to the zinc atom and the pyrano-ring is in an ideal 4C1 chair conformation. 相似文献