Synthesis of new boswellic acid derivatives as potential antiproliferative agents

Abstract

In the current investigation, a series of heterocyclic derivatives of boswellic acids were prepared along with new monomers of 3-O-acetyl-11-keto-β-boswellic acid (AKBA, 1) 11-keto-β-boswellic acid (KBA, 2) and several new bis-AKBA and KBA homodimers and AKBA-KBA heterodimers. The effects of these compounds on the proliferation of different human cancer cell lines, viz., FaDu (pharynx carcinoma), A2780 (ovarian carcinoma), HT29 (colon adenocarcinoma), and A375 (malignant melanoma), have been evaluated. Thus, KBA homodimer 21 effectively inhibited the growth of FaDu, A2780, HT29, and A375 cells with EC₅₀ values below 9?μM. In addition, compounds 7, 8, 11, 12, 15, 16, and 17 also exhibited cytotoxic effects for A2780, HT29, and A375 cancer cells. In particular, the pyrazine analog 8 was highly cytotoxic for A375 cancer cells with an EC₅₀ value of 2.1?μM.     

Synthesis and in vitro evaluation of some new pyrimidines and related condensed ring systems as potential anticancer agents

Several new pyrimidines 6–11, 18–20 , furo-, thieno-, and pyrrolo[2,3-d]pyrimidines 3, 8, 12 , triazolo-[4,3-a]pyrimidines 14, 15, 16 and tetrazolo[1,5-a]pyrimidine 17 were prepared from the known intermediate 5-(2-hydroxyethyl)-6-methyl-2-thiouracil ( 2 ). Compound 7 (4-chloro-5-(2-chloroethyl)-2-methylthio-6-methyl-pyrimidine) exhibited weak antitumor activity in vitro.     

A Theoretical design of new inorganic ring systems as potential antitumor agents

Quantum calculations of electronic structures and ring stabilities along the (NCMe)_3?x(NPMe₂)_x and (NCNMe₂)_3?x(NPMe₂)_x predict that the aziridinyl mixed terms (x = 1 and 2) of these two families may be anticancer agents even more efficient than (NCAz)₃(TEM) and (NPAz₂)₃(MYKO 63).     

Synthesis and biological evaluation of new pyrrolopyrazinone compounds as potential antitumor agents

A series of pyrrolo[1,2-a]pyrazinone compounds(5a-9f) were synthesized,and their cytotoxic activity against SKOV-3,A549.HeLa cells in vitro were evaluated by the MTT method.Some of the compounds showed potential antitumor activity against three tumor cell lines.Among them,compounds 9c and 9d showed the most potent cytotoxic activity.The preliminary mechanism of action was discussed.     

Synthesis of aryltrifluoromethylpyridazines application to the synthesis of rod‐like molecules as liquid crystals diazines part 46

Conjugated oligomers with a trifluoromethylpyridazine unit have been synthesized by Suzuki crosscoupling reaction. These oligomers could be used as building block for construction of supramolecules or as liquid crystals when they are substituted by long chain alkoxy groups.     

Capillary electrophoresis of double-stranded DNA fragments using a new fluorescence intercalating dye EvaGreen

EvaGreen is a new DNA intercalating dye successfully used in quantitative real-time PCR. In the present work, we firstly apply EvaGreen to the analysis of dsDNA by CE with LIF detection. Comparisons of EvaGreen dye with the commonly used dyes SYBR Green I and SYBR Gold were preformed in dsDNA analysis by CE. The linear range of dsDNA using EvaGreen was slightly wider than that using SYBR Gold and SYBR Green I, and the detection limits of dsDNA were not significantly different for the three dyes. Good separations of dsDNA fragments were obtained using the three dyes. Reproducibility of migration time and the peak area of dsDNA fragments with EvaGreen were better than those for SYBR Green I and SYBR Gold. The RSD values were 0.24-0.27% for migration time and 3.45-7.59% for peak area within the same day, 1.35-1.63% for migration time and 6.72-12.05% for peak area for three days. Our data demonstrated that EvaGreen is well suited for the dsDNA analysis by CE with LIF detection.     

Synthesis and in vitro studies of Gd-DTPA derivatives as new potential MRI contrast agents

A new type of dendritic molecules, Gd-DTPA derivatives, which work as a functionalized ligand coordinating gadolinium(III) ion at the center of their frameworks with different terminal moieties on the molecular surfaces, was readily synthesized with high yield. The structures were established by ¹H, ¹³C NMR, and mass spectral studies. In vitro studies showed them to have enhanced r₁ value in albumin medium and good potentiality as MRI contrast agent.     

A synthesis of potential new antiarrhythmic agents

N‐Ethylation of substituted ethyl 1H‐indole‐2‐carboxylates with iodoethane and potassium carbonate gave substituted ethyl 1‐ethyl‐1H‐indole‐2‐carboxylates. The later compounds on treatment with a range of aryl amines with varying structural complexity, gave the desired ethyl 1H‐indole‐2‐carboxamide analogues.     

Synthesis of 4-piperidazinethiols as potential antiradiation agents

The free radical addition of thioacetic acid to 1,2-dicarbethoxy-1,2,3,6-tetrahydropyridazines gave high yields of 1,2-dicarbethoxy-4-S-thiolacetoxypiperidazines. The latter compounds served as the key intermediates in the preparation of 4-piperidazinethiols. The thiolacetoxy derivatives were partially hydrolyzed to afford the related 1,2-dicarbethoxy-4-piperidazinethiols. Complete hydrolysis of the thiolacetates gave rise to 4-piperidazinethiols. Finally, lithium aluminum hydride reduction of the thiolacetoxy esters produced a series of 1,2-dimethyl-4-piperidazinethiols. Only 4-piperidazinethiol hydrochloride showed appreciable anti-radiation activity.     

Synthesis and bioactivity evaluation of new pyrimidinone-5-carbonitriles as potential anticancer and antimicrobial agents

Research on Chemical Intermediates - New series of pyrimidinone-5-carbonitriles 3a–i, 4a–e, 5a–c, 6 and 7 have been synthesized and explored for their activities as anticancer,...     

Synthesis of sydnonimine derivatives as potential trypanocidal agents

N‐(p‐Nitrophenoxy)carbonyl‐3‐morpholino‐sydnonimine (NCMS) has been prepared from 3‐morpholinosydnonimine hydrochloride. Using the Griess assay and the superoxide‐mediated reduction of ferricytochrome c, the nitric oxide (NO?) and superoxide anion (O₂?^‐) ‐ releasing properties in phosphate buffer pH 7.4 of this novel peroxynitrite donor was studied and compared with the known 3‐morpholino‐sydnonimine (SIN‐1). From compound NCMS, a series of N‐substituted sydnonimine derivatives were easily prepared that contain purine or melaminophenyl groups which specify a recognition by a trypanosomal purine transporter. The ability of these new sydnonimines to inhibit the uptake of [2³H]adenosine on Trypanosoma equiperdum was studied.     

Synthesis of some methylfurochromones as potential photochemotherapeutic agents

A number of new methylfurochromones with a linear psoralen like structure or an angular angelicin like structure were synthetized. The synthesis were performed starting from 7-hydroxychromones variously methylated on which the furan ring was built. Methyl groups have been introduced into positions which look most promising for enhancement of the photoreactivity of the compound towards DNA.     

Synthesis and metalation of trifluoromethylpyrimidines. Metalation of diazines. XVI

A new route to trifluoromethylpyrimidines is described. Lithiation of trifluoromethylpyrimidines was successfully achieved and was used to synthesize new pyrimidine derivatives. A new synthetic route to a biologically active molecule with antimycotic activities is reported.     

烷基季铵盐插层剂的合成及应用

Three novel intercalation agents were synthesized for the first time, which arose from oleic acid diethylenetriamine or triethylenetetramine 3 - chloro - 2 - hydroxypropy trimethylammonium choride (CHPTA) and chloroethanol. Organophilic vermicullites were synthesized from sodium type vermiculite by cation exchange with new intercalation agents. The results of X - ray diffraction study showed that the gallery distance of the organophilic vermiculite was enlarged from 1 nm to 5 nm or more. A new idea of making design for intercalation agent was provided.     

Synthesis of p-aminobenzamides of aminopiperidazines as potential antiarrhythmic agents

1,2-Dimethyl-4-aminopiperidazine ( 4 ), 1-(2-aminoethyl)2-methylpiperidazine ( 11 ), 2-(2-aminoethyl)-3-meth-yl-2,3-diazabicyclo[2.2.1]heptane ( 16 ), and 1,2-dimethyl-3-aminomethylpiperidazine ( 21 ) have been synthesized. Amines 4, 11 , and 16 were converted to the corresponding p-nitrobenzamides 7,12 , and 17. Catalytic reduction of the latter nitro derivatives gave the corresponding p-aminobenzamides 8,13 , and 18. For comparative studies, the acyclic analog, 4-amino-N[2-(1,1,2-trimethylhydrazino)ethyl]benzamide ( 25 ) was also synthesized. Compounds 8,13 and 25 which are analogs of procainamide were evaluated in the isolated cardiac Purkinje fiber preparation by measuring their effects on the action potential upstroke velocity.     

Synthesis of a new intercalating nucleic acid analogue with pyrenol insertions and the thermal stability of the resulting oligonucleotides towards DNA over RNA

Abstract  

A new intercalating nucleic acid monomer Y was obtained via alkylation of pyren-1-ol with (S)-(+)-2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethanol under Mitsunobu conditions followed by hydrolysis with 80% aqueous acetic acid to give a diol which was tritylated with 4,4′-dimethoxytrityl chloride followed by treatment with 2-cyanoethyltetraisopropylphosphordiamidite in the presence of N,N′-diisopropylammonium tetrazolide. In this way the monomer Y was obtained as its dimethoxytrityl-protected phosphoramidite building block for standard DNA synthesis. The corresponding oligonucleotides from Y have nearly identical hybridization properties with those of intercalating nucleic acid (INA) where neighboring oxygen and carbon atoms are interchanged in the linker. The synthesis of monomer Y avoids the use of allergic intermediates which are a problem in the synthesis of INA.     

Synthesis of diphenylcarbazoles as cytotoxic DNA binding agents

We report the synthesis of a series of novel diphenylcarbazoles designed to interact with DNA. The compounds bearing two or three dimethylaminoalkyloxy side chains were found to bind much more tightly to DNA, preferentially at AT-rich sites, than the corresponding hydroxy compounds. The DNA binding compounds exhibit potent cytotoxic activity toward P388 leukemia cells. The 3,6-diphenylcarbazole thus represent an interesting scaffold to develop antitumor agents interacting with nucleic acids.