68 research outputs found

    SYNTHESIS, CHARACTERIZATION, AND IN VITRO ANTIMALARIAL ACTIVITY OF DIHYDROXYLATION DERIVATIVES OF TRICLOSAN

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    Objective: The emergence of malaria as a global health problem over the past few decades, accompanied by the rise of chemoresistant strains ofPlasmodium falciparum, has emphasized the need for the discovery of new therapeutic drugs against this disease. In this study, enantiomericallyenriched (enantioenriched) analogs of triclosan were synthesized and evaluated for antimalarial activity against P. falciparum cultures.Methods: Enantioselective dihydroxylation of the olefin in amide seven was performed efficiently using chiral quinine ligand (DHQ)2PHAL to yieldenantioenriched dihydroxy propionamide derivative (+)-1 in moderate yields. In a similar way, the chiral quinidine ligand (DHQD)2PHAL was used asstereoselectivity agent yielded the desired enantioenriched (−)-1. The enantioenriched products were used for further in vitro assay, and accordingly thepercent enantiomeric excess (% ee) was not determined. The structures of compounds were proven by spectral data (1H NMR, 13C NMR, and mass spectra).Results: The phenol moiety at the C1 position of triclosan was chemically substituted with a methoxy group, in conjunction with an introducedstereocenter in a 2,3-dihydroxy-propionamide group at C2’ position. Unmodified triclosan inhibited the P. falciparum cultures with an IC50 value of27.2 μM. By contrast, the triclosan analogs, compounds (+)-1 and (−)-1, inhibited the P. falciparum cultures with IC50 values of 0.034 and 0.028 μM,respectively.Conclusion: Collectively, our preliminary in vitro results suggest that these triclosan analogs have potent antimalarial activity and represent apromising new treatment strategy on further development

    DESIGN, SYNTHESIS, AND CYTOTOXICITY EVALUATION OF NOVEL OPEN-CHAIN ANALOGUES OF ANTIMYCIN A 3 AS POTENTIAL ANTI-COLORECTAL CANCER AGENTS

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    Objective: Colorectal cancer is the third most common diagnosed cancer in the world. The aim of this work was to design, to synthesize, and toevaluate the novel open-chain analogues of antimycin A3 as highly potent anti-colorectal cancer agents.Methods: Our analogue synthesis was designed by modifying the nine-membered dilactone moiety of antimycin A with a simple open-chainmoiety, as well as introducing the stereocenter, and the hydroxyl groups on the side chain of the ester group. The synthesis was conducted through asequence of reactions from Boc-L-threonine by esterification, amidation, and sharpless asymmetric dihydroxylation. After completion the synthesis,cytotoxicities of the analogues were evaluated as inhibitors of colorectal HCT-116 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide cell proliferation assay.Results: Novel open-chain analogues of antimycin A were successfully synthesized in a good yield. The analogues exhibited a greater anticanceractivity against colorectal HCT-116 cells than the original antimycin A3 with 50% inhibitory concentrations ranging of 35.0-47.0 µM. The resultsindicated that the presence of stereocenter and a hydroxylated open-chain moiety in the analogues were successfully improved its anti-colorectalcancer activity.3Conclusion: Our results clearly demonstrate that the opened-chain analogues of antimycin A as a promising candidates of new anti-colorectal canceragents.Keywords: Design, Synthesis, Open-chain, Analogue, Antimycin A, Anti-colorectal cancer.3

    DESIGN AND SCREENING OF GALLIC ACID DERIVATIVES AS INHIBITORS OF MALARIAL DIHYDROFOLATE REDUCTASE (DHFR) BY IN SILICO DOCKING

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    Objective: Malaria is an infection disease caused by plasmodium parasite with high prevalence in tropic and subtropic countries. The aim of this work was to design and screening of  gallic acid derivatives as inhibitors of malarial dihydrofolate reductase (DHFR) by in silico docking.Methods: The derivatives were designed by expanding the carboxyl group of gallic acid with open-chain moiety of L-threonine-allyl esters, as well as to modify the hydroxy groups on the aromatic ring of gallic acid with methoxyl group in the derivatives.  In silico approach has been utilized in finding the potential antimalaria of gallic acid derivatives. Fourteen Gallic acid derivatives (compound 2-15) were modeled into 3D structures by  ACD Labs software. Geometry optimization and minimization of energy 3D structure of gallic acid derivatives as ligands using the MOE software.  Docking process and amino acid analysis were executed by using MOE software. Results: In silico docking study resulted in the three top-ranked compounds, namely compound 5, 8 and 12. Among those three top-ranked compounds, compound 12 (octyl gallate), exhibited the strongest interaction and greatest inhibitory activity against the receptor of malarial DHFR.Conclusion Our results clearly demonstrated that compound 12 (octyl gallate) could be developed as a promising candidate for  the new anti-malarial agent.  Â

    Microflow photochemistry: UVC-induced [2 + 2]-photoadditions to furanone in a microcapillary reactor

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    [2 + 2]-Cycloadditions of cyclopentene and 2,3-dimethylbut-2-ene to furanone were investigated under continuous-flow conditions. Irradiations were conducted in a FEP-microcapillary module which was placed in a Rayonet chamber photoreactor equipped with low wattage UVC-lamps. Conversion rates and isolated yields were compared to analogue batch reactions in a quartz test tube. In all cases examined, the microcapillary reactor furnished faster conversions and improved product qualities

    Reactive 2-Quinolones Dearomatized by Steric Repulsion between 1-Methyl and 8-Substited Groups

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    Usual 1-methyl-2-quinolone (MeQone) derivatives are not reactive because of aromatic property in the heterocyclic ring. On the other hand, 8-substituted MeQones have been proved to be highly reactive, which is caused by steric repulsion between the 1-methyl and the 8-substituted groups. When 1-methyl-3,6,8-trinitro-2-quinolone was treated with potassium (or trimethylsilyl) cyanide, cyanation proceeded at the 4-position regioselectively as a result of cine-substitution. This reaction is initiated with addition of cyanide species, and the cyanoquinolone is formed by the protonation of the resultant anionic intermediate followed by elimination of nitrous acid. The high reactivity was maintained even when one of the nitro groups on the benzene moiety was replaced by a methyl group, which afforded corresponding cine-substituted products upon treatment with potassium cyanide

    Recent Applications and Developments of Organic Azides in Total Synthesis of Natural Products

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    Organic azides have been exploited since their discovery because of their high reactivities. Various organic reactions using azides have been synthetically applied in chemical biology, pharmaceuticals, medicinal, and agricultural areas. In this review, we present some recent applications and developments of organic azides in the total synthesis of natural products (mostly within five years), especially alkaloids. We focus not only on application examples of organic azides, but also show their preparation methods including recently reported procedures concerning their decomposing and reducing methods in the syntheses of bioactive molecules

    Aqueous Catalytic Pauson-Khand-Type Reactions of Enynes with Formaldehyde: Transfer Carbonylation Involving an Aqueous Decarbonylation and a Micellar Carbonylation

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    One rhodium(I) complex catalyzes two processes in an overall Pauson-Khand-type reaction of enynes such as 1 with formaldehyde in an aqueous medium to give bicyclic cyclopentenones such as 2 in excellent yields. The use of a water-soluble phosphane ligand in conjunction with a hydrophobic phosphane ligand in the presence of a surfactant promotes the decarbonylation of formaldehyde in the aqueous phase and the carbonylation of enynes in the micellar phase
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