142-61-0Relevant articles and documents
Modulating lipophilicity of rohitukine via prodrug approach: Preparation, characterization, and in vitro enzymatic hydrolysis in biorelevant media
Kumar, Vikas,Bharate, Sonali S.,Vishwakarma, Ram A.
, p. 203 - 211 (2016)
Rohitukine is a medicinally important natural product which has inspired the discovery of two anticancer clinical candidates. Rohitukine is highly hydrophilic in nature which hampers its oral bioavailability. Thus, herein our objective was to improve the drug-like properties of rohitukine via prodrug-strategy. Various ester prodrugs were synthesized and studied for solubility, lipophilicity, chemical stability and enzymatic hydrolysis in plasma/esterase. All prodrugs displayed lower aqueous solubility and improved lipophilicity compared with rohitukine, which was in accordance with the criteria of compounds in drug-discovery. The stability of synthesized prodrugs was evaluated in buffers at different pH, SGF, SIF, rat plasma and in esterase enzyme. The rate of hydrolysis in all incubation media was dependent primarily on the acyl promoieties. Hexanoyl ester prodrug of rohitukine, 3d, was stable under chemical conditions; however it was completely hydrolyzed to rohitukine, in plasma and in esterase in 4?h. Hexanoate ester 3d appeared to be the most promising prodrug as it remained intact at gastric/intestinal pH and was completely transformed to the parent compound in plasma as desired for an ideal prodrug. The data presented herein, will help in designing prodrugs with desired physicochemical properties in future in structurally similar chemotypes.
Structure–activity relationship investigation of tertiary amine derivatives of cinnamic acid as acetylcholinesterase and butyrylcholinesterase inhibitors: compared with that of phenylpropionic acid, sorbic acid and hexanoic acid
Gao, Xiaohui,Tang, Jingjing,Liu, Haoran,Liu, Linbo,Kang, Lu,Chen, Wen
, p. 519 - 524 (2018)
In the present investigation, 48 new tertiary amine derivatives of cinnamic acid, phenylpropionic acid, sorbic acid and hexanoic acid (4d–6g, 10d–12g, 16d–18g and 22d–24g) were designed, synthesized and evaluated for the effect on AChE and BChE in vitro. The results revealed that the alteration of aminoalkyl types and substituted positions markedly influences the effects in inhibiting AChE. Almost of all cinnamic acid derivatives had the most potent inhibitory activity than that of other acid derivatives with the same aminoalkyl side chain. Unsaturated bond and benzene ring in cinnamic acid scaffold seems important for the inhibitory activity against AChE. Among them, compound 6g revealed the most potent AChE inhibitory activity (IC50 value: 3.64 μmol/L) and highest selectivity over BChE (ratio: 28.6). Enzyme kinetic study showed that it present a mixed-type inhibition against AChE. The molecular docking study suggested that it can bind with the catalytic site and peripheral site of AChE.
Enantioselective total synthesis of decytospolide A and decytospolide B using an Achmatowicz reaction
Ghosh, Arun K.,Simpson, Hannah M.,Veitschegger, Anne M.
, p. 5979 - 5986 (2018)
Enantioselective syntheses of decytospolide A and decytospolide B are described here. The current synthesis highlights an Achmatowicz rearrangement of an optically active furanyl alcohol followed by reduction of the resulting dihydropyranone hemiacetal with BF3·OEt2 and Et3SiH to provide the saturated tetrahydropyranyl alcohol directly. This reduction was investigated with a variety of other Lewis acids. The synthesis also features Noyori asymmetric transfer hydrogenation and Friedel-Crafts acylation. Overall, the synthesis provides ready access to the natural products and may be useful in the preparation of bioactive derivatives.
Stereospecific Synthesis of Glycoside Mimics Through Migita-Kosugi-Stille Cross-Coupling Reactions of Chemically and Configurationally Stable 1-C-Tributylstannyl Iminosugars
Li, Sizhe,Jaszczyk, Justyna,Pannecoucke, Xavier,Poisson, Thomas,Martin, Olivier R.,Nicolas, Cyril
, p. 470 - 483 (2021)
A process for the de novo synthesis of imino-C-glycosides is described. The methodology is based on the reaction of 1-C-stannylated iminosugars with various electrophiles under the conditions of Migita-Kosugi-Stille cross-couplings, which gives 1-C-substituted iminosugar derivatives in a stereoretentive process. The required iminoglycosyl stannanes are obtained by way of the highly stereoselective addition of tributylstannyllithium to (SR)- or (SS)-N-tert-butanesulfinyl glycosylamines, followed by an activation cyclization sequence. Most interestingly, the methodology is tunable: the configuration of the tin adduct is controlled exclusively by the tert-butanesulfinyl auxiliary, thus giving access after ring formation to ‘α’-configured or ‘β’-configured iminoglycosyl stannanes. With the subsequent stereoretentive C?C bond-forming process, the methodology allows the synthesis of pseudo anomers of imino-C-glycosyl compounds in a controlled fashion. (Figure presented.).
Supramolecular cation transporters alter root morphology in the Arabidopsis thaliana plant
Patel, Mohit B.,Negin, Saeedeh,Stavri, Ariel,Gokel, George W.
, p. 183 - 191 (2017)
Bibracchial (two-armed) 4,13-diaza-18-crown-6 lariat ether and tris(macrocycle) hydraphile synthetic amphiphiles alter root morphology in Arabidopsis thaliana plants. The effect on root structure and growth depends both on the hydraphile spacer chain length and lariat ether side chain length as well as the concentration of compound in the growth medium. In some cases a correlation to ion transport activity was apparent, but such a correlation is not always manifested. Surprisingly, planar bilayer conductance (BLM) studies showed that lariat ethers and lariat ether amides both exhibited well controlled membrane activity. Pore formation in soybean asolectin membranes occurred readily and the pores were stable and sustained. Low concentrations of active hydraphiles and lariat ethers altered the primary:lateral root density ratio, generally increasing it. The transporter-mediated alterations in lateral root density were suggestive of the activity of plant auxins such as indole-3-acetic acid and 2,4-dichlorophenoxyacetic acid, which are known to depend on cytosolic potassium ion concentrations. The hypothesis that the compounds interfere with the auxin pathway was tested and discounted by using auxin-resistant A. thaliana mutants. Rather than functioning directly as auxin mimics, ionophores affect the ion gradients producing an auxin-like effect on root development.
One-step Conversion of Amides and Esters to Acid Chlorides with PCl3
Li, Fangshao,Wu, Xiaofang,Guo, Fengzhe,Tang, Zi-Long,Xiao, Jing
supporting information, p. 4314 - 4317 (2021/07/16)
A general and efficient iodine-promoted chlorination of amides and esters with phosphorus trichloride is described. For the first time. Various inactivated amides including secondary and tertiary amides were directly converted to the corresponding acid chlorides in one-step. The substrate scope of methyl esters including aromatic and aliphatic esters was also explored under this system. This method is simple, scalable and wide in scope, which provides an approach to preparation of these acid chlorides.
Synthesis, computational studies and enzyme inhibitory kinetics of benzothiazole-linked thioureas as mushroom tyrosinase inhibitors
Ujan, Rabail,Saeed, Aamer,Ashraf, Saba,Channar, Pervaiz Ali,Abbas, Qamar,Rind, Mahboob Ali,Hassan, Mubashir,Raza, Hussain,Seo, Sung-Yum,El-Seedi, Hesham R.
, p. 7035 - 7043 (2020/08/12)
Herein, we report synthesis of a set of benzothiazole-thiourea hybrids with aromatic and aliphatic side chains (BT1 to BT9) using an elegant synthetic strategy. The newly synthesized benzothiazole-thiourea conjugates were subjected to In-vitro tyrosinase inhibition and free radical scavenging activity. Majority of the compounds indicated inhibition considerably improved than the standard; compound (Kojic acid with IC50 = 16.8320 ± 1.1600 μM) BT2 with IC50 = 1.3431 ± 0.0254 μM was found to be the best inhibitor. A non-competitive mode of inhibition of BT2 was disclosed with Ki value of 2.8 μM. In order to study enzyme-inhibitor interactions SAR analysis molecular docking was carried out. The amino groups of thiourea were involved in hydrogen bonding with Glu322 showing the bond length of 1.74 and 2.70 ?, respectively. Moreover, the coupling of π-π was displayed between benzothiazole and benzene rings of His244 and His263, respectively. The outcome of this study might help to develop new inhibitors of melanogenesis, important for cosmetic and food products. Communicated by Ramaswamy H. Sarma.
Benzimidazole tethered thioureas as a new entry to elastase inhibition and free radical scavenging: Synthesis, molecular docking, and enzyme inhibitory kinetics
Abbas, Qamar,Ashraf, Saba,Channar, Pervaiz Ali,Hassan, Abbas,Hassan, Mubashar,Rafique, Hummera,Raza, Hussain,Rind, Mahboob Ali,Saeed, Aamer,Seo, Sung-Yum,Ujan, Rabail,Ul-Hamid, Anwar
, (2021/07/02)
The porcine pancreatic elastase inhibition and free-radical scavenging play a crucial role in age progression. All the series of 10 newly synthesized benzimidazole thioureas (4a-j) were assessed for elastase inhibition and radical scavenging activity to identify the suitable anti-aging ingredient for cosmetics products. The compounds 4e, 4f, 4g, and 4h showed inhibition better than the standard, while compound 4f showed the most significant elastase inhibition with the IC50 value of 1.318 ± 0.025 μM compared with oleanic acid IC50 13.451 ± 0.014 used ±1.989 and 41.563 ± 0.824, respectively, as standard. Molecular docking studies were performed and the compound 4f showed binding energy of 7.2 kcal/mol. Kinetics studies revealed inhibition of the pancreatic elastase in a competitive manner. The relative binding energy and structure activity relationship (SAR) identified compound 4f as an effective inhibitor of porcine pancreatic elastase. Compounds 4e and 4i showed remarkable free-radical scavenging activity with SC50 values of 26.421.
Dihydropyrazole MurA enzyme inhibitor molecule as well as preparation method and application thereof
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Paragraph 0039; 0064-0066; 0068; 0087-0089; 0091; 0110-0112, (2021/05/12)
The invention provides a dihydropyrazole MurA enzyme inhibitor molecule as well as a preparation method and application thereof. The structural formula is shown in the specification, R is a direct-connected alkyl group with the chemical formula of CnH2n+1, and n is equal to 1-7. The preparation method comprises the following steps of by taking acetophenone substances with different substituent groups and 4-(4-methyl piperazinyl) benzaldehyde as raw materials, carrying out aldol condensation reaction under an alkaline condition to obtain an intermediate, and synthesizing a target compound with a structural formula by using the intermediate, hydrazine hydrate and an organic acid with an R-COOH structure. The dihydropyrazole MurA enzyme inhibitor molecule provided by the invention has a bacterial inhibition effect, has an MurA enzyme inhibition effect, and also has an effect of interfering synthesis of bacterial cell walls.
Neutrophil-Selective Fluorescent Probe Development through Metabolism-Oriented Live-Cell Distinction
Gao, Min,Lee, Sun Hyeok,Park, Sang Hyuk,Ciaramicoli, Larissa Miasiro,Kwon, Haw-Young,Cho, Heewon,Jeong, Joseph,Chang, Young-Tae
supporting information, p. 23743 - 23749 (2021/10/14)
Human neutrophils are the most abundant leukocytes and have been considered as the first line of defence in the innate immune system. Selective imaging of live neutrophils will facilitate the in situ study of neutrophils in infection or inflammation events as well as clinical diagnosis. However, small-molecule-based probes for the discrimination of live neutrophils among different granulocytes in human blood have yet to be reported. Herein, we report the first fluorescent probe NeutropG for the specific distinction and imaging of active neutrophils. The selective staining mechanism of NeutropG is elucidated as metabolism-oriented live-cell distinction (MOLD) through lipid droplet biogenesis with the help of ACSL and DGAT. Finally, NeutropG is applied to accurately quantify neutrophil levels in fresh blood samples by showing a high correlation with the current clinical method.
