Synthesis and structure elucidation of novel fused 1,2,4-triazine derivatives as potent inhibitors targeting CYP1A1 activity

Massry, Abdel Moneim El; Asal, Ahmed Mosaad; Khattab, Sherine N.; Haiba, Nesreen S.; Awney, Hala A.; Helmy, Mohamed; Langer, Vratislav; Amer, Adel

doi:10.1016/j.bmc.2012.02.041

Cited by 24 publications

(13 citation statements)

References 29 publications

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“…Compound 2 was obtained by reacting 4‐amino 6‐benzyl‐3‐mercapto‐1,2,4‐triazin‐5(4 H )‐one ( 1 ) with hydrazine hydrate in ethanol as a modified method for that reported in the literature . The mass spectrum of compound 2 indicates a molecular ion peak at m/z = 232 (M + 25.3), corresponding to the molecular formula C 10 H 12 N 6 O and a base peak at m/z = 50 (100.0%).…”

Section: Resultsmentioning

confidence: 99%

“…White needles (0.84 g, 85%); mp 265–266°C (lit. mp °C 254–255 ); [ethanol]; R f = 0.14 [pet. ether (60:80)/ethyl acetate (4:1)]; IR (KBr): ν/cm −1 = 3330, 3283, 3226 (2NH 2 ), 3184 (NH), 2910 (CH 2 ), 1685 (C═O amide), and 1660 (C═C); MS (EI, 70 eV) m/z (%) = 232 (M + 25.3), 216 (3.8), 185 (1.6), 186 (5.8), 117 (24.1), 91 (96.7), 76 (67.4), 53 (27.6), 50 (100.0).…”

Section: Methodsmentioning

confidence: 99%

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Synthetic Approach to Some New Annulated 1,2,4‐Triazine Skeletons with Antimicrobial and Cytotoxic Activities

Hamama

El‐Bana

Shaaban

et al. 2018

Journal of Heterocyclic Chem

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in Wiley Online Library (wileyonlinelibrary.com).The synthesis of some triazolotriazine, tetrazolotriazine, triazinotetrazine, and triazinotetrazepinoindole by the reaction of 4-amino-6-benzyl-3-hydrazinyl-1,2,4-triazin-5(4H)-one (2) with different reagents is described. The synthesized compounds were screened for their antimicrobial activity using the minimum inhibition concentration method by serial dilution technique. Two of these compounds showed higher activity than that of standard drug, and they were further evaluated for their cytotoxic activities against human cancer cells (MCF-7, HCT116, and HepG2), which indicate strong effect on these cancer cell lines. J. Heterocyclic Chem., 55, 971 (2018). and the carbonyl group of acid to form hydrazone intermediate, which underwent a cyclization reaction between the secondary amine and the hydroxyl group of the acid function affording 3, following pathway A. The constitution of 3 was deduced from its spectral data. Its 1 H NMR spectrum showed a singlet signal at δ = 2.49 and 6.05 ppm corresponding to CH 3 and NH 2 , Scheme 2. Action of 1,2-diketonic compounds on the triazino hydrazine derivative 2 to form the corresponding hydrazones 7, 8, 9, and 11. Scheme 1. Heterocyclization reaction of 2 with various reagents. Scheme 3. Alkylation of hydrazine derivative 2 with halo compounds. 972W.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Synthetic Approach to Some New Annulated 1,2,4‐Triazine Skeletons with Antimicrobial and Cytotoxic Activities

Hamama

El‐Bana

Shaaban

et al. 2018

Journal of Heterocyclic Chem

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“…Data showed that compound 226e (R = Me, Ar = Ph, Ar 1 = 4-ClC 6 H 4 ) displayed the highest inhibitory effects among all tested 1,2,4-triazine derivatives. Furthermore, docking analysis showed that these compounds bind only at the interface of substrate recognition site 2 (SRS2) and (SRS6) at the outer surface of the protein, and that amino-acids ASN214, SER216 and ILE462 participate in the binding of these compounds through H-bonds [226]. A one-pot four-component approach was established for site selective synthesis of 1,3,6-trisubstituted 3,6-diunsaturated (3Z,6Z)-2,5-diketopiperazine derivatives 229 (38-60% yield) and 230 (31-64% yield), mediated by double-aldolic condensations between pyrazine 228 and two equivalents of aldehydes type 1A/1B, involving also a mono-alkylation reaction in the same reaction pot, Scheme 89.…”

Section: Miscellaneous Of Diverse Heterocyclic Systems With Potentialmentioning

confidence: 99%

Synthesis of Biologically Active Molecules through Multicomponent Reactions

et al. 2020

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Focusing on the literature progress since 2002, the present review explores the highly significant role that multicomponent reactions (MCRs) have played as a very important tool for expedite synthesis of a vast number of organic molecules, but also, highlights the fact that many of such molecules are biologically active or at least have been submitted to any biological screen. The selected papers covered in this review must meet two mandatory requirements: (1) the reported products should be obtained via a multicomponent reaction; (2) the reported products should be biologically actives or at least tested for any biological property. Given the diversity of synthetic approaches utilized in MCRs, the highly diverse nature of the biological activities evaluated for the synthesized compounds, and considering their huge structural variability, much of the reported data are organized into concise schemes and tables to facilitate comparison, and to underscore the key points of this review.Molecules 2020, 25, 505 2 of 71 acetylcholinesterase inhibitors, anti-HIV, antimicrobial, antioxidant, anti-mycobacterial and anticancer activities ( Figure 1). It is noteworthy that 64% and 16% of the supporting literature found for this review correspond to heterocyclic structures with anticancer and antimicrobial activities, respectively. Scheme 2. Three-component synthesis of 3,4-dihydropyrimidinones/thiones type 7 under microwave irradiation, for anti-inflammatory activity.Patil et al., reported a one-pot pseudo-five-component synthesis of highly functionalized tetrahydropyridines 9 using Cu(OTf) 2 as catalyst, Scheme 3. In vitro anti-inflammatory activity of the obtained compounds 9 was determined against matrix metalloproteinases (MMPs) as MMP-2 and MMP-9 by using gelatin zymography [29]. Scheme 3. Multicomponent Cu(OTf) 2 catalyzed synthesis of substituted tetrahydropyridines 9 for anti-inflammatory activity.A highly diastereoselective synthesis (exclusively the cis isomer is formed), of chromeno β-lactam hybrids 13/14 was also achieved by an efficient one-pot three-component reaction between either 5,5-dimethylcyclohexane-1,3-dione (10a) or 4-hydroxycoumarin (10b), diverse benzaldehydes 11 and malononitrile (12), in the presence of DABCO under reflux conditions (Scheme 4). Scheme 4. Three-component synthesis of β-lactam hybrids 13/14 for anti-inflammatory activity.The synthesized compounds (13 in 80-95% yield) and (14 in 82-95% yield) were screened for anti-inflammatory activity (as well as for anticancer activity, please see Section 3.13.13. Compound 13b (Ar = 4-ClC 6 H 4 , Ar 1 = 4-MeC 6 H 4 ) was the most active of all the chromeno β-lactam hybrids 13/14 tested, with a 19.8 anti-inflammatory ratio, although, it resulted less active than the reference drug dexamethasone corticosteroid used for the treatment of rheumatoid and skin inflammation [30].

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“…Interestingly, 1,2,4‐triazine derivatives have been reported for their diverse biological activities such as anticancer , antibacterial , antidiabetic , antifungal , antimalarial , neuroprotective agents , anticonvulsant , and antiviral activities.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Docking Study of Pyrimidine–Triazine Hybrids for GABA Estimation in Animal Epilepsy Models

Sahu

Siddiqui

Naim

et al. 2017

Archiv der Pharmazie

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A series of new pyrimidine-triazine hybrids (4a-t) was designed and synthesized, from which potent anticonvulsant agents were identified. Most of the compounds exhibited promising anticonvulsant activity against the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests, along with minimal motor impairment with higher safety compared to the standard drugs, phenytoin and carbamazepine. In the series, 5-(4-(4-fluorophenyl)-6-(4-hydroxyphenyl)-2-thioxo-5,6-dihydropyrimidin-1(2H)-yl)-1,2-dihydro-1,2,4-triazin-3(6H)-one (4o) and 5-(6-(4-hydroxy-3-methoxyphenyl)-4-(4-hydroxyphenyl)-2-thioxo-5,6-dihydropyrimidin-1(2H)-yl)-1,2-dihydro-1,2,4-triazin-3(6H)-one (4s) emerged as most potent anticonvulsant agents with median doses of 22.54 and 29.40 mg/kg (MES ED ), 285.02 and 293.42 mg/kg (scPTZ ED ), and 389.11 and 412.16 mg/kg (TD ), respectively. Docking studies were also performed for all synthesized compounds to get insight into the binding pattern toward the GABA receptor as a possible mechanism of their anticonvulsant action, and in silico ADME studies were carried out to predict the safety and stability of the molecules. The increased GABA level in the experimental animals in the neurochemical estimation assay confirmed their GABAergic modulating activity. The most potent compounds were also evaluated for their neurotoxic and hepatotoxic effects. Fortunately, they did not show any sign of neurotoxicity or hepatotoxicity, suggesting that they have a broad spectrum of anticonvulsant activity with a large safety margin. Together, this research suggested that 4o and 4s may serve as leads in the discovery and development of new anticonvulsant drugs.

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Synthesis and structure elucidation of novel fused 1,2,4-triazine derivatives as potent inhibitors targeting CYP1A1 activity

Cited by 24 publications

References 29 publications

Synthetic Approach to Some New Annulated 1,2,4‐Triazine Skeletons with Antimicrobial and Cytotoxic Activities

Synthetic Approach to Some New Annulated 1,2,4‐Triazine Skeletons with Antimicrobial and Cytotoxic Activities

Synthesis of Biologically Active Molecules through Multicomponent Reactions

Design, Synthesis, and Docking Study of Pyrimidine–Triazine Hybrids for GABA Estimation in Animal Epilepsy Models

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