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

Abstract

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.

Bicyclic 5-6 Systems With One Bridgehead (Ring Junction) Nitrogen Atom: Four Extra Heteroatoms 2:2

“…More specifically, the construction of triazolotriazines has been performed in acetic acid under reflux to produce the 6-methyl derivative 376 in good yield. 142 Condensation of 375 with triethyl orthoformate in refluxing ethanol in the presence of a catalytic amount of acetic acid furnished triazolotriazine 377. 143 Alternatively, thioxotriazolotriazinone 378 could be obtained by treatment of 375 with carbon disulfide in pyridine under reflux.…”

Anticancer Compounds Based on Isatin-Derivatives: Strategies to Ameliorate Selectivity and Efficiency

“…A set of hybrids of isatin with hydrazines and hydrazones moieties have been extensively described in the literature, comprehending natural products ( Le Goff and Ouazzani, 2014 ) and synthetic derivatives ( El-Faham et al, 2015 ) due to their biological and, especially, their anticancer properties. These studies include different derivatives, as coumarins ( Nasr et al, 2014 ), triazines ( Hamama et al, 2018 ), pyrazole-based heterocycles ( Ismail and El-sayed, 2019 ), exhibiting good activity versus diverse tumor cells (colon, leukemia, breast, kidney). Some of these hydrazine- and hydrazone derivatives of isatin are shown in Figure 5 .…”

“…These studies were supported by molecular modeling and crystallography that helped to understand the interaction between the tested compounds and the CDK2 protein ( Bramson et al, 2001 ). Recently, these compounds were also reported as inhibitors of human carbonic anhydrase isoenzyme IX (hCA IX), exhibiting a better activity than the standard CA inhibitor acetazolamide (AAZ) used as reference ( Hamama et al, 2018 ).…”

Indole/isatin‐containing hybrids as potential antibacterial agents

“…Besides the abovementioned indole hybrids, some other conjugates such as hybrid 98 (MIC: 25.1 and 34.2 μg/ml, MIC values for ampicillin: 10.5 and 16.2 μg/ml against S. pneumoniae and E. coli ) also showed a certain activity and the enriched SAR may pave the way for the further rational design of more active candidates. [ 197–203 ]…”