- Discovery of ortho-carborane-conjugated triazines as selective topoisomerase I/II inhibitors
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The cell growth inhibition profile of 2,4-(2-methyl-ortho-carboranyl)-4- (dimethylamino)-1,3,5-triazine (TAZ-6) was found to be similar to that of ICRF-193, a topoisomerase II inhibitor, as revealed by COMPARE analysis (correlation coefficient (r)≤0.724). Various mono-and di-ortho-carborane- substituted 1,3,5-triazines were synthesized based on the structure of TAZ-6 and tested for their ability to inhibit cell growth and the activities of topoisomerases I and II. Among the compounds synthesized, 3c, 4c, and 4f completely inhibited topoisomerase I activity without affecting topoisomerase II activity, whereas 3a and 3d completely inhibited topoisomerase II activity without affecting topoisomerase I activity, at 100μM.
- Nakamura, Hiroyuki,Shoji, Atsushi,Takeuchi, Ayano,Ban, Hyun Seung,Lee, Jong-Dae,Yamori, Takao,Kang, Sang Ook
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- Discrete assembly of synthetic peptide-DNA triplex structures from polyvalent melamine-thymine bifacial recognition
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We have designed a 21-residue α-peptide that simultaneously recognizes two decadeoxyoligothymidine (dT10) tracts to form triplexes with a peptide-DNA strand ratio of 1:2. The synthetic peptide side chain displays 10 melamine rings, which provide a bifacial thymine-recognition interface along the length of the 21-residue peptide. Recognition is selective for thymine over other nucleobases and drives the formation of ternary peptide· [dT10]2 complexes as well as heterodimeric peptide· [dT10C10T10] hairpin structures with triplex stems.
- Zeng, Yingying,Pratumyot, Yaowalak,Piao, Xijun,Bong, Dennis
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- Design and synthesis of a series of melamine-based nitroheterocycles with activity against trypanosomatid parasites
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The parasites that give rise to human African trypanosomiasis (HAT) are auxotrophs for various nutrients from the human host, including purines. They have specialist nucleoside transporters to import these metabolites. In addition to uptake of purine nucleobases and purine nucleosides, one of these transporters, the P2 transporter, can carry melamine derivatives; these derivatives are not substrates for the corresponding mammalian transporters. In this paper, we report the coupling of the melamine moiety to selected nitro heterocycles with the aim of selectively delivering these compounds to the parasites. Some compounds prepared have similar in vitro trypanocidal activities as melarsoprol, the principal drug used against late-stage HAT, with 50% growth inhibitory concentrations in the submicromolar range. Selected compounds were also evaluated in vivo in rodent models infected with Trypanosoma brucei brucei and T. brucei rhodesiense and showed pronounced activity and in two cases were curative without overt signs of toxicity. Compounds were also tested against other trypanosomatid pathogens, Leishmania donovani and Trypanosoma cruzi, and significant activity in vitro was noted for T. cruzi against which various nitro heterocycles are already registered for use.
- Baliani, Alessandro,Bueno, Gorka Jimenez,Stewart, Mhairi L.,Yardley, Vanessa,Brun, Reto,Barrett, Michael P.,Gilbert, Ian H.
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- Application of heterocyclic thiol compound in preparation of antitumor drugs
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The heterocyclic thiol compound provided by the invention shows good anti-hepatoma cells. Human breast cancer cells or human non-small cell lung cancer cell activity lays a foundation for screening and development of new drugs, and has good practical value.
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Paragraph 0024-0025; 0031-0032
(2021/08/25)
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- Design, synthesis, anticancer, antibacterial, and antifungal evaluation of 4-aminoquinoline-1,3,5-triazine derivatives
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A series of 4-aminoquinoline 1,3,5-triazine derivatives were synthesized and evaluated for anticancer activity against cancer cell lines HeLa, MCF-7, HL-60, HepG2 where these derivatives exert significant anticancer activity. The molecules found nontoxic against MCF-12A. The molecules also showed potent inhibition of EGFR-TK as compared to eroltinib in enzyme-based assay. The newly synthesized derivatives were screened for their in vitro antibacterial and antifungal activity against Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, Proteus vulgaris, Escherichia coli, Pseudomonas aeruginosa and Candida albicans, Aspergillus niger, Aspergillus fumigatus using cefixime and fluconazole as standard. Antibacterial screening results suggest that compound 7c showed potent activity against S. aureus, P. aeruginosa, and P. vulgaris. In antifungal screening, compound 7b showed significant activity against A. niger, A. fumigatus and moderate activity against C. albicans.
- Bhat, Hans Raj,Ghosh, Surajit Kumar,Masih, Anup,Shakya, Anshul,Singh, Udaya Pratap
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- N-Methylmelamines: Synthesis, Characterization, and Physical Properties
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N-Methylmelamines have recently gained importance as valuable compounds for manufacturing modified melamine formaldehyde resins and other polymer building blocks. A great advantage of these polymers is the reduction of the carcinogenic formaldehyde. Selecting the polymerization processes (e.g., substance polymerization, polymerization in solution) and controlling the polymerization reaction and properties of these novel materials requires knowledge of the properties of the individual melamine derivatives used as new building blocks. All possible permutations of N-methylmelamines were prepared, and reaction progress was monitored by GC/MS. 2,4,6-Tris(dimethylamino)-1,3,5-triazine was prepared to complete the series; this is, however, also a possible byproduct in various synthesis routes. The reaction conditions were optimized to obtain high yields of each derivative with the highest possible purity. The substances were characterized by NMR and IR spectroscopy, mass spectrometry, elemental analysis, and single-crystal X-ray diffraction. In addition, physical properties, such as solubility, melting points, and pKb values, were determined. The number of amino-, methylamino-, and dimethylamino groups has a significant effect on these properties. In summary, we found that by increasing the number of amino- and methylamino groups, solubility and pKb increase. With increasing number of amino groups, the compounds tend to form hydrogen bonds, and thus, the melting point shifts to higher temperature ranges where they start to decompose.
- List, Manuela,Puchinger, Helmut,Gabriel, Herbert,Monkowius, Uwe,Schwarzinger, Clemens
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p. 4066 - 4075
(2016/06/09)
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- MK2 INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 0304
(2016/04/09)
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- Targeting the erythrocytic and liver stages of malaria parasites with s-triazine-based hybrids
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A diversity-oriented library of s-triazine-based hybrids was screened for activity against the chloroquine-resistant Plasmodium falciparum W2 strain. The most striking result was sub-micromolar activity against cultured erythrocytic-stage parasites of hybrid molecules containing one or two 8-aminoquinoline moieties. These compounds were not clearly toxic to human cells. The most effective blood-schizontocidal s-triazine derivatives were then screened for activity against the liver stage of malaria parasites. The s-triazine hybrid containing two 8-aminoquinoline moieties and one chlorine atom emerged as the most potent against P. berghei liver-stage infection, active in the low nanomolar region, combined with good metabolic stability in rat liver microsomes. These results indicate that s-triazine-8-aminoquinoline-based hybrids are excellent starting points for lead optimization as dual-stage antimalarials.
- Rodrigues, Catarina A. B.,Frade, Raquel F. M.,Albuquerque, Inês S.,Perry, Maria J.,Gut, Jiri,Machado, Marta,Rosenthal, Philip J.,Prudêncio, Miguel,Afonso, Carlos A. M.,Moreira, Rui
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p. 883 - 890
(2015/05/05)
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- Novel S-triazine accommodated 5-benzylidino-4-thiazolidinones: Synthesis and in vitro biological evaluations
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In order to explore various pharmacological effects associated with S-triazine accommodated 5-benzylidino-4-thiazolidinones, a series of compounds based on 5-benzylidene-2-[4-(4,6-bis-dimethylamino-[1,3,5]triazin-2-ylamino)-phenylimino]-thiazolidin-4-one
- Rana, Aniruddhasinh M.,Trivedi, Pooja,Desai, Kishor R.,Jauhari, Smita
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p. 4320 - 4336
(2015/04/22)
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- A novel series of potent cytotoxic agents targeting G2/M phase of the cell cycle and demonstrating cell killing by apoptosis in human breast cancer cells
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Breast cancer, a leading cause of mortality in women, warrants the development and biological evaluation of new anticancer agents. A novel series of thiopyridine triazine derivatives was synthesized and investigated in the human breast cancer cell line, MDA-MB-468. SM40, the most potent derivative, induced a G2/M arrest and apoptosis with a possible involvement of p53. The cytotoxicity of SM40 was also examined against the NCI 60 cell line panel and its potency was rationalized using molecular modeling. Results suggest that SM40 is a promising cytotoxic agent.
- Mandal, Soma,Berube, Gervais,Asselin, Eric,Mohammad, Iqbal,Richardson, Vernon J.,Gupta, Atul,Pramanik, Saroj K.,Williams, Arthur L.,Mandal, Sanat K.
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p. 4955 - 4960
(2008/02/12)
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- Synthesis and aromatase-inhibitory activity of imidazolyl-1,3,5-triazine derivatives
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Triamino-substituted 1,3,5-triazine derivatives were synthesized and tested for inhibitory activities against the aromatase of human placental microsomes and the cytochrome P450 side chain cleavage of cholesterol (P450(SCC)) of pig adrenal mitochondria. The compounds having imidazolyl and tertiary amino groups as substituents in the 1,3,5-triazine ring showed significant aromatase-inhibitory activity. Among them, compounds 17, 23, 26, 27 and 28 were more active than the reference compound, CGS 16949A. The inhibitory activities of these compounds against P450(SCC) were much weaker than their aromatase-inhibitory activities. These compounds may be regarded as selective aromatase inhibitors.
- Matsuno, Toshiyuki,Kato, Masanobu,Tsuchida, Yoshio,Takahashi, Masayuki,Yaguchi, Sin-Ichi,Terada, Sumio
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p. 291 - 296
(2007/10/03)
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- Novel pyrimidine and 1,3,5-triazine hypolipidemic agents
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New compounds were synthesized by changing the substituents of a trisubstituted pyrimidine, i.e., [[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]thio]acetic acid, a potent hypolipidemic agent, impaired, however, by a marked hepatomegaly-inducing effect. The structural variations led to the subsidence (14b, i.e., 4-chloro-2-(dimethylamino)-6-[(2,3-dimethylphenyl)amino]pyrimidine) or to the reduction (18b, [[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]amino]acetic acid) of said untoward effect but still maintained the hypolipidemic effect that, although markedly decreased, still proves significant for serum cholesterol and triglycerides (18b) or for serum triglycerides only (14b).
- d'Atri,Gomarasca,Resnati,Tronconi,Scolastico,Sirtori
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p. 1621 - 1629
(2007/10/02)
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- The Synthesis of Alkyl- and Aryl-Substituted 1,3,5-Triazines
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The reaction of chloromethyleneiminium salts with N-cyanoamidines provides a new and versatile route to alkyl- and aryl-substituted 1,3,5-triazines.Variation of substituents in the starting materials allows the synthesis of monoaryl-, diaryl-, alkyl-aryl- and certain mono- and di-alkyl-1,3,5-triazines bearing a variety of other substituents including hydrogen, chlorine and O-, S- and N-radicals.The generally good yields, ready availability of starting materials, and the scope and facility of the reaction make it the method of choice for the synthesis of 1,3,5-triazines with these substitution patterns.
- Harris, Roger L. N.
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p. 623 - 634
(2007/10/02)
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