- A convenient synthesis of triazine-based dendrons and dendrimers via a convergent approach and a study of their interactions with tetrafluoro- benzoquinone
-
A convenient, efficient and convergent approach to prepare triazine-based dendrons and dendrimers is developed. The steric hindrance resulting from the presence of dioctylamino moieties in the peripheral regions allows the synthesis of soluble dendrons without employing protection and deprotection steps. The triazine-based dendrimers are prepared via reaction of N,N′- dimethylethane-1,2-diamine with the dendrons in a ratio of 1:2. Interactions of the dendrimers with tetrafluorobenzoquinone led to the appearance of new broad bands, red-shifted by approximately 180 nm, in the absorbance spectra. Georg Thieme Verlag Stuttgart.
- Lai, Long-Li,Hsu, Hui-Chu,Hsu, Shun-Ju,Cheng, Kung-Lung
-
-
Read Online
- Hybrid Quinazoline 1,3,5-Triazines as Epidermal Growth Factor Receptor (EGFR) Inhibitors with Anticancer Activity: Design, Synthesis, and Computational Study
-
We report a series of hybrid quinazoline-1,3,5-triazine derivatives as EGFR inhibitors, which were synthesised and tested by using a variety of in vitro, in silico, and in vivo techniques. The derivatives were found to be active against different cancer cell lines and nontoxic against normal ones, with compounds 7 c, 7 d, 7 e, and 7 j being the most potent ones. The derivatives were also evaluated for angiogenesis inhibition potency in chicken eggs, and molecular docking and dynamics simulation studies were carried out to elucidate the fundamental substituent groups essential for their bioactivity. Additionally, a SAR study of the derivatives was performed for future compound optimisation. These studies suggested that the derivatives have a high affinity towards EGFR with favourable pharmacological properties. The most active compound (7 e) was further evaluated for in vivo anticancer activity against DMBA-induced tumours in female Sprague-Dawley rats as well as its effects on plasma antioxidant status, biotransformation enzymes, and lipid profile. The study suggested that 7 e has lead properties against breast cancer and can serve as a starting compound for further development of anti-EGFR compounds.
- Pathak, Prateek,Rimac, Hrvoje,Grishina, Maria,Verma, Amita,Potemkin, Vladimir
-
p. 822 - 838
(2020/12/07)
-
- Application of heterocyclic thiol compound in preparation of antitumor drugs
-
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.
- -
-
Paragraph 0024-0025; 0028-0229
(2021/08/25)
-
- Synthesis and characterization of new series of 1,3-5-Triazine hydrazone derivatives with promising antiproliferative activity
-
A new series of s-triazine hydrazone derivatives was prepared based on the reaction of 6-hydrazino-2,4-disubstituted-s-triazine with p-substituted benzaldehyde derivatives using a straightforward synthetic pathway. The antiproliferative activity of all synthesized compounds was evaluated against two human cancer cell lines; breast cancer MCF-7 and colon carcinoma HCT-116 using MTT assay. Among all, 11 compounds have shown strong to moderate antiproliferative activity with IC50 values in the range 1.01–18.20 μM in MCF-7 and 0.97–19.51 μM in HCT-116. The best results were obtained with 4,4’-(6-(2-(pyridin-2-ylmethylene)hydrazinyl)-1,3,5-triazine-2,4-diyl) dimorpholine 11 (IC50 = 1.0 μM and 0.98 μM in MCF-7 and HCT-116 cell lines, respectively). The substituents on the s-triazine core as well as the substituent at the benzylidene moiety have a great effect on the antiproliferative activity. Whereas compounds containing dimorpholino-striazine derivatives 8a–e showed more potent antiproliferative in MCF-7 compared to their analogs 7a–f (compounds containing two-piperidine rings), compounds containing one piperidine and one morpholine ring 9a–f showed better IC50 values in the range 10.4–22.2 μM. On the other hand, compounds containing two-piperidine rings 7a–f showed more potent antiproliferative in HCT-116 (IC50 values in the range 8.8–19.5 μM) than their analogs 8a–e and 9a–f.
- Al Rasheed, Hessa H.,Malebari, Azizah M.,Dahlous, Kholood A.,El-Faham, Ayman
-
-
- Design and synthesis of mono-and di-pyrazolyl-s-triazine derivatives, their anticancer profile in human cancer cell lines, and in vivo toxicity in zebrafish embryos
-
s-Triazine is considered a privileged structure, as it is found in several FDA-approved drugs. In the framework of our ongoing medicinal chemistry project based on the use of s-triazine as a scaffold, we synthesized a series of mono- and di-pyrazolyl-s-triazine derivatives and tested them against four human cancer cell lines, namely Human breast carcinoma (MCF 7 and MDA-MB-231), hepatocellular carcinoma (HepG2), colorectal carcinoma (LoVo), and leukemia (K562). The cell viability assay revealed that most of the s-triazine compounds induced cytotoxicity in all four types of human cancer cell lines, however, compounds 4a, and 6g, both of them have a piperidine moiety in their structure were most effective. These two compounds affected the cell viability of cancer cells, with IC50 values within the range between 5 to 9 μM. The cell cycle analysis showed that 4a and 6g induced S and G2/M phase cell cycle arrest in K562 cells. This could be the mechanism by which these molecules induced cytotoxicity in tested cancer cells. The prepared compounds were tested in zebrafish embryos to evaluate in vivo and developmental toxicity of the pyrazolyl-s-triazine derivatives in animals. None of the derivatives were lethal in the concentration range tested.
- Farooq, Muhammad,Sharma, Anamika,Almarhoon, Zainab,Al-Dhfyan, Abudalla,El-Faham, Ayman,Taha, Nael Abu,Wadaan, Mohammad A.M.,Torre, Beatriz G. de la,Albericio, Fernando
-
p. 457 - 464
(2019/03/27)
-
- Synthesis, X-ray crystal structures, and preliminary antiproliferative activities of new s-triazine-hydroxybenzylidene hydrazone derivatives
-
We herein report a new small library of Schiff-base compounds that encompasses s-triazine and (2 or 4)-hydroxylbenzylidene derivatives. These compounds were synthesized through a hydrazone linkage connecting both the s-triazine and hydroxybenzylidene deri
- Barakat, Assem,El-Senduny, Fardous F.,Almarhoon, Zainab,Al-Rasheed, Hessa H.,Badria, Farid A.,Al-Majid, Abdullah Mohammed,Ghabbour, Hazem A.,El-Faham, Ayman
-
-
- Synthesis, Characterization, and Tautomerism of 1,3-Dimethyl Pyrimidine-2,4,6-Trione s-Triazinyl Hydrazine/Hydrazone Derivatives
-
1,3,5-Triazines and pyrimidine-2,4,6-triones belong to that class of compounds which are well known in literature for possessing wide range of biological activities. Here, we report a new family of compounds that encompasses these two structures. The unio
- Sharma, Anamika,Jad, Yahya,Siddiqui, Mohammed R. H.,De La Torre, Beatriz G.,Albericio, Fernando,El-Faham, Ayman
-
-
- MK2 INHIBITORS AND USES THEREOF
-
The present invention provides compounds, compositions thereof, and methods of using the same.
- -
-
Paragraph 0303
(2016/04/09)
-
- Ultrasonic promoted synthesis of novel s-triazine-Schiff base derivatives; molecular structure, spectroscopic studies and their preliminary anti-proliferative activities
-
Novel series of s-triazine-Schiff base derivatives were synthesized employing ultrasonic irradiation and characterized by NMR (1H and 13C), FT-IR, and elemental analysis. The use of ultrasonic irradiation has allowed the preparation of the target products with better yields in shorter reaction time and excellent purities compared to the conventional heating. X-ray single crystal diffraction experiments verified the molecular structure of four from the new prepared s-triaizne-Schiff base derivatives. The molecular structures of the studied compounds are computerized using DFT/B3LYP method. The effects of substituent at the triazine and phenyl ring on the electronic and spectroscopic properties of the studied compounds were also investigated. The natural atomic charges showed that pipridino-s-triazine derivatives are richer in electrons than those having morpholino derivatives. The anti-proliferative effects for the prepared compounds were tested against three different cancer cell lines.
- El-Faham, Ayman,Soliman, Saied M.,Ghabbour, Hazem A.,Elnakady, Yasser A.,Mohaya, Talal A.,Siddiqui, Mohammed R.H.,Albericio, Fernando
-
p. 121 - 135
(2016/07/07)
-
- Synthesis and preliminary biological evaluation of 1,3,5-triazine amino acid derivatives to study their MAO inhibitors
-
Three series of 4,6-dimethoxy-, 4,6-dipiperidino- and 4,6-dimorpholino-1,3,5-triazin- 2-yl) amino acid derivatives were synthesized and characterized. A preliminary study for their monoamine oxidase inhibitory activity showed that compounds 7, 18, and 25 had MAO-A inhibition activity comparable to that of the standard clorgyline, with apparently more selective inhibitory activity toward MAO-A than MAO-B and no significant acute toxicity.
- Khattab, Sherine N.,Khalil, Hosam H.,Bekhit, Adnan A.,El-Rahman, Mohamed Mokbel Abd,El-Faham, Ayman,Albericio, Fernando
-
p. 15976 - 15988
(2015/12/01)
-
- Synthesis, in vitro antiplasmodial activity and cytotoxicity of a series of artemisinin-triazine hybrids and hybrid-dimers
-
A series of artemisinin-triazine hybrids and hybrid-dimers were synthesized and their in vitro antimalarial activity against the chloroquine sensitive (CQS), the gametocytocidal (NF54) and the choroquine resistant (CQR) Dd2 strains of Plasmodium falciparu
- Cloete, Theunis T.,De Kock, Carmen,Smith, Peter J.,N'Da, David D.
-
p. 470 - 481
(2014/03/21)
-
- Convenient syntheses of cyanuric chloride-derived NHC ligands, their Ag(i) and Au(i) complexes and antimicrobial activity
-
Convenient syntheses of mono- and bis-imidazolium 1,3,5-triazine derivatives bearing piperidine and morpholine substituents are reported. In situ deprotonation of the mono-imidazolium salts and reaction with Ag2O or Au(tht)Cl (tht = tetrahydrothiophene) precursors affords the corresponding Ag(NHC)Cl and Au(NHC)Cl carbene complexes. In the presence of Ag(i) or Au(i) salts the bis-imidazolium pincers eliminate the imidazolium group to afford -OMe or -NMe2 substituted triazines depending on the solvent used. In solution, the Ag(i) and Au(i) complexes show a barrier to rotation about the Ctriazine-Namine bonds, with calculated ΔG ≠ barriers in the region of 70 kJ mol-1. Single crystal X-ray structures of several of the proligands and their corresponding Ag(i) and Au(i) complexes were obtained. These universally reveal an extended, rigidly planar π-conjugated network between the triazine core, imidazolium/ imidazolylidene substituents and exocyclic amine functions, to which the origin of the rotational barrier observed in solution is attributed. Only very weak Ntriazine-metal interactions are observed in the solid state, as indicated by small deviations of the CNHC-Ag-Cl bond angles from 180°and also supported by DFT calculations on the Ag(NHC)Cl complex (NHC = 4,6-dipiperidinyl-2-methylimidazolylidene triazine). Preliminary antimicrobial susceptibility studies against five microorganisms (methicillin resistant Staphylococcus aureus NCTC 13277, S. aureus NCTC 6571, Pseudomonas aeruginosa NCTC 10662, Proteus mirabilis NCTC 11938 and Candida albicans ATCC 90028) show that the above triazine-based Ag-NHC complexes are active antimicrobial and antifungal agents.
- Almalioti, Foteini,MacDougall, James,Hughes, Stephen,Hasson, Mohammed M.,Jenkins, Robert L.,Ward, Benjamin D.,Tizzard, Graham J.,Coles, Simon J.,Williams, David W.,Bamford, Sarah,Fallis, Ian A.,Dervisi, Athanasia
-
supporting information
p. 12370 - 12380
(2013/09/02)
-
- Antimalarial activity and docking studies of novel bi-functional hybrids derived from 4-aminoquinoline and 1,3,5-triazine against wild and mutant malaria parasites as pf-DHFR inhibitor
-
Bi-functional conjugates comprised of 4-aminoquinoline and 1,3,5-triazine were synthesized through facile synthetic routes. These compounds were rigorously screened for determination of their antimalarial activity against wild and mutant cultured Plasmodium falciparum. The results disclosed that the conjugates have considerable antimalarial activity against both wild and mutant parasites with marked variation on changing the pattern of substitutions. The observed activity profiles were additionally substantiated by docking studies on both wild and quadruple mutant P. falciparum dihydrofolate reductase thymidylate synthase (pf-DHFR-TS).
- Bhat, Hans Raj,Singh, Udaya Pratap,Gahtori, Prashant,Ghosh, Surajit Kumar,Gogoi, Kabita,Prakash, Anil,Singh, Ramendra K.
-
p. 2942 - 2952
(2013/05/08)
-
- 4-Aminoquinoline-1,3,5-triazine: Design, synthesis, in vitro antimalarial activity and docking studies
-
A series of hybrid 4-aminoquinoline 1,3,5-triazine derivatives was synthesized and their chemical structure were confirmed by 1H-NMR, 13C-NMR, FT-IR and mass spectrometric analyses. In vitro antimalarial activity of these compounds was evaluated against chloroquine-sensitive (3D-7) and chloroquine resistant (RKL-2) strains of P. falciparum. Results showed that all compounds had considerable antimalarial activity against both the strains and further docking studies were performed on both wild type (1J3I.pdb) and quadruple mutant (N51I, C59R, S108 N, I164L, 3QG2.pdb) pf-DHFR-TS to quantify the structural parameter necessary for the activity.
- Bhat, Hans Raj,Singh, Udaya Pratap,Gahtori, Prashant,Ghosh, Surajit Kumar,Gogoi, Kabita,Prakash, Anil,Singh, Ramendra K.
-
p. 2654 - 2662
(2013/09/12)
-
- Design, facile synthesis, antibacterial activity and structure-activity relationship of novel di- and tri-substituted 1,3,5-triazines
-
Due to overwhelming generation of drug resistant microorganisms, there is an urgent need to develop novel chemotherapeutic agents. In continuation of our research on discovery of novel heterocyclic scaffolds from 1,3,5-triazine, present study deals with design and development of some novel di- and tri-substituted 1,3,5-triazine derivatives. The synthesis of title analogues were accomplished by SNAr reaction and subsequently underwent rigorous antibacterial screening against a panel of representative Gram-negative and Gram-positive bacteria. Screening results revealed that minor structural variation may induce drastic changes in activity. Whereas, amine bridge and piprazine was termed as pivotal structural fragments necessary for generation and escalation of bio-activity. The structures of newly synthesized compounds were ascertained on the basis of their analytical and spectral profiles.
- Ghosh, Surajit Kumar,Saha, Ashmita,Hazarika, Bornali,Singh, Udaya Pratap,Bhat, Hans Raj,Gahtori, Prashant
-
experimental part
p. 329 - 335
(2012/05/20)
-
- Discovery of new 1,3,5-triazine scaffolds with potent activityagainst Mycobacterium tuberculosis H37Rv
-
A series of eighty one 2,4,6-trisubstituted-1,3,5-triazines were synthesized and evaluated in vitro for the growth inhibition of Mycobacterium tuberculosis H37Rv. Fifteen compounds from this series exhibited good to moderate activity with an MIC in the ra
- Sunduru, Naresh,Gupta, Leena,Chaturvedi, Vinita,Dwivedi, Richa,Sinha, Sudhir,Chauhan, Prem M.S.
-
experimental part
p. 3335 - 3345
(2010/08/06)
-
- Identification and optimisation of novel and selective small molecular weight kinase inhibitors of mTOR
-
A pharmacophore mapping approach, derived from previous experience of PIKK family enzymes, was used to identify a hit series of selective inhibitors of the mammalian target of rapamycin (mTOR). Subsequent refinement of the SAR around this hit series based
- Menear, Keith A.,Gomez, Sylvie,Malagu, Karine,Bailey, Christine,Blackburn, Kristel,Cockcroft, Xiao-Ling,Ewen, Sally,Fundo, Alexandra,Gall, Armelle Le,Hermann, Gesine,Sebastian, Luisa,Sunose, Mihiro,Presnot, Thomas,Torode, Eleanor,Hickson, Ian,Martin, Niall M.B.,Smith, Graeme C.M.,Pike, Kurt G.
-
scheme or table
p. 5898 - 5901
(2010/08/22)
-
- Synthesis and bioevaluation of hybrid 4-aminoquinoline triazines as a new class of antimalarial agents
-
The emergence and rapid spread of chloroquine resistant strains of Plasmodium falciparum has dramatically reduced the chemotherapeutic options. Towards this goal, a series of new class of hybrid 4-aminoquinoline triazines were synthesized and screened aga
- Kumar, Ashok,Srivastava, Kumkum,Raja Kumar,Puri,Chauhan, Prem M.S.
-
scheme or table
p. 6530 - 6533
(2009/09/06)
-
- Novel inhibitors of Erm methyltransferases from NMR and parallel synthesis
-
The Erm family of methyltransferases confers resistance to the macrolide-lincosamide-streptogramin type B (MLS) antibiotics through the methylation of 23S ribosomal RNA. Upon the methylation of RNA, the MLS antibiotics lose their ability to bind to the ribosome and exhibit their antibiotic activity. Using an NMR-based screen, we identified a series of triazinecontaining compounds that bind weakly to ErmAM. These initial lead compounds were optimized by the parallel synthesis of a large number of analogues, resulting in compounds which inhibit the Erm-mediated methylation of rRNA in the low micromolar range. NMR and X-ray structures of enzyme/inhibitor complexes reveal that the inhibitors bind to the S- adenosylmethionine binding site on the Erm protein. These compounds represent novel methyltransferase inhibitors that serve as new leads for the reversal of Erm-mediated MLS antibiotic resistance.
- Hajduk, Philip J.,Dinges, Jürgen,Schkeryantz, Jeffrey M.,Janowick, David,Kaminski, Michele,Tufano, Michael,Augeri, David J.,Petros, Andrew,Nienaber, Vicki,Zhong, Ping,Hammond, Rachel,Coen, Michael,Beutel, Bruce,Katz, Leonard,Fesik, Stephen W.
-
p. 3852 - 3859
(2007/10/03)
-
- Synthesis and aromatase-inhibitory activity of imidazolyl-1,3,5-triazine derivatives
-
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
-
p. 291 - 296
(2007/10/03)
-