- RETRACTED ARTICLE: Design, synthesis, and biological evaluation of heterotetracyclic quinolinone derivatives as anticancer agents targeting topoisomerases
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A series of thiochromeno[2,3-c]quinolin-12-one derivatives with various substitutions were synthesized and evaluated as topoisomerase (Topo) inhibitors. Six (8, 10, 12, 14, 19, and 26) of 23 compounds showed strong inhibitory activities against Topo-media
- Lee, Jiann-Fong,Chang, Ting-Yu,Liu, Zheng-Fang,Lee, Nian-Zhe,Yeh, Yen-Hsiu,Chen, Yi-Song,Chen, Tsung-Chih,Chou, Hao-Syun,Li, Tsai-Kun,Lee, Sung-Bau,Lin, Mei-Hsiang
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- Competitive behavior of nitrogen based axial ligands in the oxovanadium(IV)-salen catalyzed sulfoxidation of phenylmercaptoacetic acid
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The sulfoxidation of twelve phenylmercaptoacetic acids (PMAA) by H2O2 catalyzed by three oxovanadium(IV)-salen complexes, having varied substituents on PMAA and salen with regard to their position, size and inductive effect, has been performed spectrophotometrically in 100percent acetonitrile medium. Three nitrogen bases (NB), pyridine (Py), imidazole (ImH) and 1-methylimidazole (MeIm), were used as axial ligands. It has been found that the rate of sulfoxidation is not only tuned by the substituents on PMAA and salen, but it is also varied by the addition of nitrogen bases. The observed order of retardation found among the different nitrogen bases is ImH > MeIm > Py. The rate of reaction decreases with the increase in concentration of the NB axial ligands. The strongly binding ImH shows the least reactivity. Hydroperoxovanadium(V)-salen has been proposed as the sole active oxidizing species. A detailed mechanistic study reveals that the low rate constant values in the presence of the nitrogen base is due to the existence of competition of NB with H2O2 and PMAA during the formation of active species and the coordination of PMAA with active species, respectively. Both electron donating and electron withdrawing substituents on PMAA retard the sulfoxidation rate significantly. The Hammett correlation between the rate constants and substituent constants shows a non-linear concave downward curve which is explained by the existence of two different rate determining steps within the same mechanism; coordination of PMAA with the active species for electron withdrawing substituents and transfer of oxygen to PMAA for electron donating substituents. All the experimental observations are explained by proposing a suitable mechanism.
- Kavitha, C.,Subramaniam, P.
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- FMS-LIKE TYROSINE KINASE INHIBITORS
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The present invention relates to Fms-like tyrosine kinase (FLT3) inhibitors. The present invention provides novel 4-quinolinone derivatives used as FLT3 inhibitors and for treatment and/or prevention of tumors.
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Page/Page column 25; 29; 34
(2020/03/31)
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- Sulfur-containing andrographolide derivative and pharmaceutical composition and synthesis method thereof and application of sulfur-containing andrographolide derivative in preparation of medicine for treating prostatic cancers
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The invention relates to an andrographolide derivative shown in the following general formula (I) or general formula (II) (please see the formula in the description) and a preparation method thereof and a composition containing the compound shown in the g
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Paragraph 0032; 0033
(2017/03/25)
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- Synthesis of thioether andrographolide derivatives and their inhibitory effect against cancer cells
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A series of novel thioether andrographolide derivatives were synthesized by incorporating various aromatic (or heteroaromatic) substituents into C-12 or 14-OH. A total of 38 andrographolide derivatives were prepared and evaluated for their in vitro inhibi
- Liu, Yi,Liang, Ren-Ming,Ma, Qing-Ping,Xu, Kai,Liang, Xin-Yong,Huang, Wei,Sutton, Robert,Ding, Jie,O'Neil, Paul M.,Cheng, Chun-Ru
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p. 1268 - 1274
(2017/07/07)
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- Electrophilic and nucleophilic pathways in ligand oxide mediated reactions of phenylsulfinylacetic acids with oxo(salen)chromium(V) complexes
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The mechanism of oxidative decarboxylation of phenylsulfinylacetic acids (PSAA) by oxo(salen)Cr(V)+ ion in the presence of ligand oxides has been studied spectrophotometrically in acetonitrile medium. Addition of ligand oxides (LO) causes a red shift in the λmax values of oxo(salen) complexes and an increase in absorbance with the concentration of LO along with a clear isobestic point. The reaction shows first-order dependence on oxo(salen)-chromium(V)+ ion and fractional-order dependence on PSAA and ligand oxide. Michaelis-Menten kinetics without kinetic saturation was observed for the reaction. The order of reactivity among the ligand oxides is picoline N-oxide > pyridine N-oxide > triphenylphosphine oxide. The low catalytic activity of TPPO was rationalized. Both electron-withdrawing and electron-donating substituents in the phenyl ring of PSAA facilitate the reaction rate. The Hammett plots are non-linear upward type with negative ρ value for electron-donating substituents, (ρ- = -0.740 to -4.10) and positive ρ value for electron-withdrawing substituents (ρ+ = +0.057 to +0.886). Non-linear Hammett plot is explained by two possible mechanistic scenarios, electrophilic and nucleophilic attack of oxo(salen)chromium(V)+-LO adduct on PSAA as the substituent in PSAA is changed from electron-donating to electron-withdrawing. The linearity in the log k vs. Eox plot confirms single-electron transfer (SET) mechanism for PSAAs with electron-donating substituents.
- Subramaniam,Sugirtha Devi,Anbarasan
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p. 164 - 173
(2016/06/06)
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- Importance of ground state stabilization in the oxovanadium(IV)-salophen mediated reactions of phenylsulfinylacetic acids by hydrogen peroxide – Non-linear Hammett correlation
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A systematic study on the oxidative decarboxylation of a series of phenylsulfinylacetic acids (PSAA) by hydrogen peroxide with four oxovanadium(IV)-salophen catalysts in 100% acetonitrile medium is presented. The hydroperoxovanadium(V)-salophen generated from the reaction mixture is identified as the bonafide active oxidizing species. Introduction of electron donating groups (EDG) in the oxovanadium(IV)-salophen catalyst and electron withdrawing groups (EWG) in PSAA enhances the reactivity, whereas EWG in the catalyst and EDG in PSAA have a retarding effect on the reaction. A Hammett correlation displays a non-linear downward curvature, which consists of two intersecting straight lines and the ρ value shifts from small positive to moderately high as the substituents change from EWG to EDG. The importance of the ground state stabilization of PSAA is inferred from a linear Yukawa–Tsuno plot. Based on the observed substituent effects and the spectral changes, a mechanism involving electrophilic attack of PSAA on the nucleophilic peroxo oxygen atom of the vanadium complex in the rate determining step followed by oxygen atom transfer is proposed.
- Subramaniam,Jeevi Esther Rathnakumari,Janet Sylvia Jaba Rose
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p. 496 - 503
(2016/07/21)
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- Modulation of catalytic activity by ligand oxides in the sulfoxidation of phenylmercaptoacetic acids by oxo(salen)chromium(V) complexes
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Mechanism of sulfoxidation of eleven para-substituted phenyl mercaptoacetic acids (PMAAs) by three oxo(salen)chromium(V)+PF6?complexes in the presence of different ligand oxides (LOs) such as triphenylphosphine oxide, pyridine N-oxide and 4-picoline N-oxide have been studied spectrophotometrically in 100% acetonitrile medium. Spectral and kinetic profiles establish the formation of adduct, O[dbnd]Cr(V)(salen)+-LO as the reactive intermediate in the catalytic cycle. The rate of sulfoxidation is found to be enhanced significantly by the addition of LOs and introduction of substituent in PMAA and salen complex. Both electron releasing and electron withdrawing substituents in the substrate and oxidant facilitate the rate of sulfoxidation. Correlation with Hammett constants yields a non-linear concave upward curve. Based on the experimental results and substituent effects two different mechanisms, a direct oxygen atom transfer (DOT) for PMAAs with electron withdrawing substituents and a single electron transfer for PMAAs with electron donating substituents have been postulated.
- Subramaniam,Anbarasan,Sugirtha Devi,Ramdass
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- A paradigm shift in rate determining step from single electron transfer between phenylsulfinylacetic acids and iron(III) polypyridyl complexes to nucleophilic attack of water to the produced sulfoxide radical cation: a non-linear Hammett
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Mechanism of oxidative decarboxylation of phenylsulfinylacetic acids (PSAAs) by iron(III) polypyridyl complexes in aqueous acetonitrile medium has been investigated spectrophotometrically. An initial intermediate formation between PSAA and [Fe(NN)3]3+ is confirmed from the observed Michaelis–Menten kinetics and fractional order dependence on PSAA. Significant rate retardation with concentration of [Fe(NN)3]3+ is rationalized on the basis of coordination of a water molecule at the carbon atom adjacent to the ring nitrogen of the metal polypyridyl complexes by nucleophilic attack at higher concentrations. Electron-withdrawing and electron-releasing substituents in PSAA facilitate the reaction and Hammett correlation gives an upward ‘V’ shaped curve. The apparent upward curvature is rationalized based on the change in the rate determining step from electron transfer to nucleophilic attack, by changing the substituents from electron-releasing to electron-withdrawing groups. Electron-releasing substituents in PSAA accelerate the electron transfer from PSAA to the complex and also stabilize the intermediate through resonance interaction leading to negative reaction constants (ρ). Conversely, electron-withdrawing groups, while retarding the electron transfer exert an accelerating effect on the nucleophilic attack of H2O which leading to low magnitude of ρ+ compared to high ρ? values of electron-releasing groups. Marcus theory is applied, and a fair agreement is seen with the experimental values. Copyright
- Subramaniam, Perumal,Janet Sylvia Jaba Rose, Jebamoney,Jeevi Esther Rathinakumari, Rajasingh
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p. 496 - 504
(2016/09/21)
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- Spectral and mechanistic investigation of Oxidative Decarboxylation of Phenylsulfinylacetic Acid by Cr(VI)
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The oxidative decarboxylation of phenylsulfinylacetic acid (PSAA) by Cr(VI) in 20% acetonitrile - 80% water (v/v) medium follows overall second order kinetics, first order each with respect to [PSAA] and [Cr(VI)] at constant [H+] and ionic strength. The reaction is acid catalysed, the order with respect to [H+] is unity and the active oxidizing species is found to be HCrO3+. The reaction mechanism involves the rate determining nucleophilic attack of sulfur atom of PSAA on chromium of HCrO3+ forming a sulfonium ion intermediate. The intermediate then undergoes a,β-cleavage leading to the liberation of CO2. The product of the reaction is found to be methyl phenyl sulfone. The operation of substituent effect shows that PSAA containing electron-releasing groups in the meta- and para-positions accelerate the reaction rate while electron withdrawing groups retard the rate. An excellent correlation is found to exist between log k2 and Hammett s constants with a negative value of reaction constant. The p value decreases with increase in temperature evidencing the high reactivity and low selectivity in the case of substituted PSAAs.
- Subramaniam, Perumal,Selvi, Natesan Thamil,Devi, Soundarapandian Sugirtha
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- ARYLSULFANYL COMPOUNDS AND COMPOSITIONS FOR DELIVERING ACTIVE AGENTS
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Compounds and compositions for the delivery of active agents are provided. Methods of administration and preparation are also provided.
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Page/Page column 56
(2008/06/13)
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- Syntheses and in vitro evaluation of arylsulfone-based MMP inhibitors with heterocycle-derived zinc-binding groups (ZBGs)
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Several classes of arylsulfone-based MMP-2/-9 inhibitors utilizing 6- to 8-membered heterocyclic rings as zinc-binding groups (ZBGs) have been synthesized and their enzyme inhibitory activities were evaluated. Although a number of 6- and 7-membered hetero
- Zhang, Yue-Mei,Fan, Xiaodong,Yang, Shyh-Ming,Scannevin, Robert H.,Burke, Sharon L.,Rhodes, Kenneth J.,Jackson, Paul F.
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p. 405 - 408
(2008/12/23)
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- HETEROCYCLIC DERIVED METALLOPROTEASE INHIBITORS
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This invention provides novel heterocyclic derived matrix metalloprotease inhibitors of the formula: and pharmaceutical compositions comprising same, useful for treating disorders ameliorated by antagonizing matrix metalloproteases. This invention also provides therapeutic and prophylactic methods using the instant pharmaceutical compositions.
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Page/Page column 58
(2008/06/13)
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- KINETICS AND MECHANISM OF OXIDATION OF (ARYLTHIO)ACETIC ACIDS BY PYRIDINIUM HYDROBROMIDE PERBROMIDE
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Oxidation of several monosubstituted (phenylthio)acetic acids (PTAA) by pyridinium hydrobromide perbromide (PHPB) was studied in aqueous acetic acid.The reaction is first order with respect to PHPB.Michaelis-Menten type kinetics are observed with respect to (arylthio)acetic acid.The effect of solvent composition indicates that the transition state is more polar than the reactants.The formation constants of the intermediate substrate-PHPB complexes and the rates of their decomposition were determined at different temperatures.The rates of oxidation of para and meta-substituted (phenylthio)acetic acids were correlated with Hammett's substituent constants.The ρ value is -1.60 at 35 deg c.The rates of oxidation of ortho substituted compounds are correlated with Charton's triparametric equation.A mechanism involving the decomposition of the intermediate complex in the slow rate-determining step affording a sulphonium ion which hydrolyses in a subsequent fast step to the sulphoxide is proposed.
- Karunakaran, K.,Elango, K. P.
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p. 429 - 434
(2007/10/02)
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- Photoredox reactions of polypyridyl chromium (III) complexes with arylthioacetic acids in acetonitrile and aqueous media
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The reductive quenching reactions of ,Cr(NN)33+ (NN = 2,2'-bipyridyl, 4,4'-dimethyl-2,2'-bipyridyl and 1,10-phenanthroline) with arylthioacetic acids in acetonitrile and arylthioacetate ions in aqueous media have been studied. The substantial difference in k(q) values between the acetonitrile and aqueous media is traced to the difference in the origin of electron for the reduction of Cr(III) complexes i.e., sulphur in acetonitrile and carboxylate ion in aqueous medium.
- Gnanaraj,Rajagopal,Srinivasan
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p. 9447 - 9456
(2007/10/02)
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- FLUORINATED TRICYCLIC NEUROLEPTICS WITH PROLONGED ACTION: DERIVATIVES AND ANALOGUES OF 2-(4-(7-FLUORO-2-ISOPROPYL-10,11-DIHYDRODIBENZOTHIEPIN-11-YL)PIPERAZINE-1-YL)ETHANOL
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The preparation of 4-fluoro-2-nitrobenzonitrile (V), an intermediate in the synthesis of the title compound I, from 4-fluoro-2-nitroaniline via 5-fluoro-2-iodonitrobenzene (VII) was elaborated.Syntheses of 1,1,1,3,3,3-hexadeutero-2-propyl (XX) and 1,3,4-trideutero (XXVIII) analogues of compound I from hexadeuteroacetone, and pentadeuterobromobenzene, respectively, were carried out.Compound I was esterified with acetic anhydride, decanoic acid and 3,4,5-trimethoxybenzoyl chloride to give the esters II-IV.Acylation of compound XXX with acetyl chloride, 4-fluorophenoxyacetyl chloride and (4-fluorophenylthio)acetyl chloride and the following reduction of the amides with lithium aluminium hydride gave compounds XXXII, XXXIX, and XL.Substitution reactions of 11-chloro-7-fluoro-2-isopropyl-10,11-dihydrodibenzothiepin with the corresponding N-monosubstituted piperazines resulted in compounds XXXIII-XXXV, XXXVII, XXXVIII, XLI and XLII.Alkylation of XXX with 2-(2-chloroethyl)-1,3-dioxolane afforded compound XXXVI.Pharmacological testing of the new compounds, derivatives and analogues of the neuroleptic agent isofloxythepin (I), for discoordinating and cataleptic activities, showed especially for compounds II, XXXIV and XXXVI very intensive and long-lasting effects.The decanoate III has properties of a depot neuroleptic agent.
- Protiva, Miroslav,Jilek, Jiri,Rajsner, Miroslav,Sindelar, Karel,Bartl, Vaclav,et al.
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p. 1811 - 1833
(2007/10/02)
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