T:Toxic;
96-34-4Relevant academic research and scientific papers
Discovery of novel triazolophthalazine derivatives as DNA intercalators and topoisomerase II inhibitors
Sakr, Helmy,Ayyad, Rezk R.,El-Helby, Ali A.,Khalifa, Mohamed M.,Mahdy, Hazem A.
, (2021/02/16)
A new series of triazolophthalazine derivatives was designed and synthesized as topoisomerase II (Topo II) inhibitors and DNA intercalators. The synthesized derivatives were evaluated in vitro for their cytotoxic activities against three human cancer cell lines: HepG2, MCF-7, and HCT-116 cells. Compound IXb was the most potent counterpart with IC50 values of 5.39 ± 0.4, 3.81 ± 0.2, and 4.38 ± 0.3 μM, as it was about 1.47, 1.77, and 1.19 times more active than doxorubicin (IC50 = 7.94 ± 0.6, 6.75 ± 0.4, and 5.23 ± 0.3 μM) against HepG2, MCF-7, and HCT-116 cells, respectively. Additionally, the binding affinity of the synthesized compounds toward the DNA molecule was assessed using the DNA/methyl green assay. Compound?IXb showed an excellent DNA binding affinity with an IC50 value of 27.16 ± 1.2 μM, which was better than that of the reference drug doxorubicin (IC50 = 31.02 ± 1.80 μM). Moreover, compound IXb was the most potent member among the tested compounds when investigated for their Topo II inhibitory activity. Furthermore, compound IXb induced apoptosis in HepG2 cells and arrested the cell cycle at the G2/M phase. Additionally, compound IXb showed Topo II poisoning effects at 2.5 μM and Topo II catalytic inhibitory effects at 5 and 10 μM. Finally, molecular docking studies were carried out against the DNA–Topo II complex and DNA, to investigate the binding patterns of the designed compounds.
New Diesters Derived from Piperine: In silico Study and Evaluation of Their Antimicrobial Potential
Barbosa-Filho, José M.,Brand?o, Maria Cláudia R.,Lima, Edeltrudes O.,Lira, Bruno F.,Neto, Hermes D.,Souza, Helivaldo D. S.,Trindade, Emmely O.,de Athayde-Filho, Petr?nio F.
, p. 1668 - 1678 (2020/10/09)
Piperine, previously extracted from black pepper (Piper nigrum L.), was used as a precursor for the synthesis of twelve new diester derivatives. The final products were obtained through the bimolecular nucleophilic substitution reaction (SN2) of the alkyl 2-chloroacetates and the salt of piperic acid, obtained from the basic hydrolysis of piperine. The compounds were synthesized with yields of 55-84% and characterized by infrared spectroscopy and 1H and 13C nuclear magnetic resonance. The evaluation of the compounds’ potential as new drug candidates was done through an in silico study of ADME properties (absorption, distribution, metabolization and excretion) and evaluation of antimicrobial activity against bacterial strains (Staphylococcus aureus and Pseudomonas aeruginosa), yeasts (Candida albicans and Candida tropicalis) and filamentous fungi (Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger). The in silico study showed that the compounds were good drug candidates and antimicrobial evaluation demonstrated that 9 of the 12 compounds exhibited a minimum inhibitory concentration (MIC) ranging 1024-256 μg mL?1
Synthesis, in silico Study and Antimicrobial Evaluation of New Diesters Derived from Phthaloylglycine
Alves, Francinara S.,Barbosa-Filho, José M.,Cordeiro, Laísa V.,Huang, Min-Fu N.,Lima, Edeltrudes O.,Neto, Hermes Diniz,Souza, Helivaldo D. S.,Trindade, Emmely O.,de Athayde-Filho, Petr?nio F.,de Lima, Priscila S. V.,de Oliveira, Rafael F.,de Sousa, Abra?o P.
, p. 953 - 962 (2020/10/14)
New diesters derived from phthaloylglycine (7a-7i) were synthesized and their structures characterized by infrared, 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. The compounds were evaluated in an in silico study, which demonstrated positive features indicating a possible drug candidate. The diesters showed antifungal activity ranging from moderate to strong against strains of Candida. Compounds 7a, 7b, 7c, 7e and 7i had a moderate minimum inhibitory concentration (MIC) of 1024 μg mL?1 against all fungal strains, while 7h showed a very good MIC of 256 μg mL?1 against Candida albicans, Candida parapsilosis and Candida krusei and 64 μg mL?1 against Candida tropicalis. However, only 7h and 7i were able to inhibit bacterial growth of strains of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Escherichia coli with an MIC of 1024 μg mL?1
Preparation method of 2-methyl-4-chloro-phenoxyacetic acid
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Paragraph 0028; 0032; 0033, (2020/09/21)
The invention belongs to the technical field of pesticide synthesis, and particularly relates to a 2-methyl-4-chloro-phenoxyacetic acid preparation method, which uses o-methylphenol sodium as a reactant, and uses an organic phase methyl chloroacetate solution as a reaction solvent in a condensation reaction. The method has the advantages that the method is simple; in the condensation reaction, anorganic phase methyl chloroacetate solution is used as a reaction solvent to replace a water phase in the traditional technology; and the organic phase can be continued to the subsequent chlorinationreaction, so that the problems of decomposition of sodium chloroacetate and low reaction yield can be solved, no wastewater can be generated in the production of MCPA sodium salt, the yield can be greatly improved, and the method is a green and environment-friendly synthesis method.
Green synthesis method of methyl cyanoacetate
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Paragraph 0029-0041, (2020/10/30)
The invention discloses a green synthesis method of methyl cyanoacetate. The preparation process comprises the following steps: heating methyl chloroacetate and acetone cyanohydrin to 40-100 DEG C inthe absence of a catalyst and a solvent, and reacting to obtain methyl cyanoacetate. Acetone cyanohydrin serves as a cyaniding reagent and directly reacts with methyl chloroacetate to generate methylcyanoacetate, no other solvent or catalyst is needed, the yield is high, and the production cost is greatly reduced.
Preparation method of phenoxyacetic ester
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Paragraph 0052; 0053; 0056; 0058; 0060; 0062, (2019/01/08)
The invention provides a preparation method of phenoxyacetic ester, wherein the preparation method includes the following steps: A) carrying out esterification reaction of acetic acid and alcohol to obtain acetic ester; B) introducing chlorine gas into acetic ester, and carrying out reaction to obtain chloroacetic ester; C) dehydrating a phenol compound and alkaline hydroxide into a salt in an organic solvent to obtain a salt of the phenol compound; D) after salt formation, mixing with chloracetic ester prepared in the step B), and carrying out condensation reaction to obtain phenoxyacetic ester, wherein the organic solvent is a mixture of any two kinds of toluene, xylene, chlorobenzene, phenol, butanol and isobutanol. The phenol is dehydrated into the salt in the mixed organic solvent, the system still maintains a uniform state in the dehydration process, continuous production is achieved, the dehydration efficiency is high and the efficiency of the whole production process is high. Moreover, the raw materials are easy to obtain, the production period is short, water is not needed in the reaction process, the energy consumption is low, the production cost is low, the yield of acetic acid is 99% or more, and the total yield of phenol can reach 99% or more.
Self-assembled orthoester cryptands: Orthoester scope, post-functionalization, kinetic locking and tunable degradation kinetics
L?w, Henrik,Mena-Osteritz, Elena,Von Delius, Max
, p. 4785 - 4793 (2018/06/07)
Dynamic adaptability and biodegradability are key features of functional, 21st century host-guest systems. We have recently discovered a class of tripodal supramolecular hosts, in which two orthoesters act as constitutionally dynamic bridgeheads. Having previously demonstrated the adaptive nature of these hosts, we now report the synthesis and characterization-including eight solid state structures-of a diverse set of orthoester cages, which provides evidence for the broad scope of this new host class. With the same set of compounds, we demonstrated that the rates of orthoester exchange and hydrolysis can be tuned over a remarkably wide range, from rapid hydrolysis at pH 8 to nearly inert at pH 1, and that the Taft parameter of the orthoester substituent allows an adequate prediction of the reaction kinetics. Moreover, the synthesis of an alkyne-capped cryptand enabled the post-functionalization of orthoester cryptands by Sonogashira and CuAAC "click" reactions. The methylation of the resulting triazole furnished a cryptate that was kinetically inert towards orthoester exchange and hydrolysis at pH > 1, which is equivalent to the "turnoff" of constitutionally dynamic imines by means of reduction. These findings indicate that orthoester cages may be more broadly useful than anticipated, e.g. as drug delivery agents with precisely tunable biodegradability or, thanks to the kinetic locking strategy, as ion sensors.
Preparation method for 2,4-dichlorophenoxyacetic acid
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Paragraph 0051; 0052, (2018/09/08)
The invention provides a preparation method for 2,4-dichlorophenoxyacetic acid, belonging to the technical field of organic synthesis. The preparation method comprises the following steps: a) reactinghalogenated acetate with 2,4-dichlorophenolate in the presence of a phase-transfer catalyst so as to obtain 2,4-dichlorophenoxyacetate; and b) hydrolyzing 2,4-dichlorophenoxyacetate so as to obtain 2,4-dichlorophenoxyacetic acid. According to the invention, oil-phase halogenated acetate reacts with 2,4-dichlorophenolate under the action of the phase-transfer catalyst to prepare 2,4-dichlorophenoxyacetate, and then 2,4-dichlorophenoxyacetate is hydrolyzed to obtain 2,4-dichlorophenoxyacetic acid and corresponding alcohols. Under the action of the phase-transfer catalyst, few hydrolysis by-products are produced during a reaction, fast reaction speed and high conversion rate and yield are obtained, and the amount of produced waste water is low; so industrial application of the preparation method can be easily implemented.
Preparation method for 2,4-dichlorophenoxyacetic acid
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Paragraph 0050; 0051, (2018/09/08)
The invention provides a preparation method for 2,4-dichlorophenoxyacetic acid, belonging to the technical field of organic synthesis. The preparation method comprises the following steps: a) reactinghalogenated acetate with an anhydrous 2,4-dichlorophenolate solid so as to obtain 2,4-dichlorophenoxyacetate; and b) hydrolyzing 2,4-dichlorophenoxyacetate so as to obtain 2,4-dichlorophenoxyacetic acid. According to the invention, the anhydrous 2,4-dichlorophenolate solid reacts with halogenated acetate to prepare 2,4-dichlorophenoxyacetate, and then 2,4-dichlorophenoxyacetate is hydrolyzed to obtain 2,4-dichlorophenoxyacetic acid and corresponding alcohols. The mass transfer effect of a solid-liquid reaction in the invention is good; few hydrolysis by-products are produced during the reaction; fast reaction speed and high conversion rate and yield are obtained; the amount of produced waste water is low; so industrial application of the preparation method can be easily implemented.
Preparation method for 2,4-dichlorophenoxyacetic acid
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Paragraph 0034; 0035, (2018/09/29)
The invention provides a preparation method for 2,4-dichlorophenoxyacetic acid. The preparation method comprises the following steps: a) reacting haloacetic acid with 2,4-dichlorophenolate in a strong-polarity solvent so as to obtain 2,4-dichlorophenoxy acetate; and B) hydrolyzing 2,4-dichlorophenoxyacetate so as to obtain 2,4-dichlorophenoxyacetic acid. According to the invention, the strong-polarity solvent is utilized, so the mass transfer effect of the reaction is improved, reaction time is reduced, the reaction is more complete, and the conversion rate and yield of the reaction are greatly improved.
