Barbiturate- and Thiobarbituarte-Based <i>s</i>-Triazine Hydrazone Derivatives with Promising Antiproliferative Activities

Rasheed, Hessa Al H Al H; Dahlous, Kholood A.; Sharma, Anamika; Sholkamy, Essam Nageh; El‐Faham, Ayman; Torre, Beatriz G. de la; Alberício, Fernando

doi:10.1021/acsomega.0c00468

Cited by 25 publications

(19 citation statements)

References 40 publications

(61 reference statements)

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“…These results could reflect the importance of a piperidine substituent on the triazine ring as a less polar group for optimum activity in cancer cells. These results are consistent with our previously reported results, where the piperidine derivatives showed better activity compared to their corresponding morpholine analogs [ 33 , 34 , 36 ].…”

Section: Resultssupporting

confidence: 93%

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Synthesis, Anti-proliferative Activity, and Molecular Docking Study of New Series of 1,3-5-Triazine Schiff Base Derivatives

et al. 2020

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Based on the use of s-triazine as a scaffold, we report here a new series of s-triazine Schiff base derivatives and their anti-proliferative activity against two cancer cell lines: human breast carcinoma (MCF-7), and colon cancer (HCT-116) compared with tamoxifen as a reference compound. Several derivatives exhibited growth inhibition activity in the sub-micromolar range. The results reveal that the s-triazine Schiff base derivatives showed varied activities and that the substituents on the s-triazine core have a great effect on the anti-proliferative activity. Compounds with a piperidino and benzylamino substituent on the s-triazine moiety 4b and 4c were most effective in both cell lines compared to the reference compound used. In addition, compound 4b has a para chlorine atom on the benzylidine residue, demonstrating the most potent activity with IC50 values of 3.29 and 3.64 µM in MCF-7 and HCT-116, respectively. These results indicate that in general, the nature of the substituents on the triazine core and the type of substituent on the benzilyldene ring significantly influenced the anti-proliferative activity. The results obtained from the anti-proliferative activity and the molecular docking study indicate that s-triazine-hydrazone derivatives may be an excellent scaffold for the development of new anti-cancer agents.

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Section: Resultssupporting

confidence: 93%

“…2-Hydrazino-4,6-disubstituted-1,3,5-triazine derivatives 2 were synthesized first following the reported methods [ 26 , 32 , 33 , 34 , 36 ] and used directly without further purification into the next step.…”

Section: Methodsmentioning

confidence: 99%

Synthesis, Anti-proliferative Activity, and Molecular Docking Study of New Series of 1,3-5-Triazine Schiff Base Derivatives

et al. 2020

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“…Filtration and drying afforded the desired products (14 derivatives) [21]. Hydrazone derivatives bearing a s-triazine core (Series 3 and 4) were synthesized [13,15,24]. Disubstituted-monochloro triazines (d-MCTs) were synthesized using piperidine and morpholine as nucleophiles.…”

Section: Synthesis Of S-triazine Derivativesmentioning

confidence: 99%

“…Series 3 and 4 (Schiff base analogs) [ 13 , 24 ] and Series 6 (Pyrazole) [ 23 ] were evaluated for anticancer activity against Lung carcinoma (A549), Hepatocellular carcinoma (HepG2), Adenocarcinoma (MCF-7), Human breast cancer (MCF, MDA-MB-231), Human colorectal carcinoma (LoVo, HCT-116), and Human leukemia (K562). Out of all the 34 derivatives, Figure 4 shows the derivatives possessing Schiff base analogs, which showed higher antiproliferative/anticancer activity than pyrazole derivatives ( Figure 4 ).…”

Section: Biological Evaluationmentioning

confidence: 99%

“…[4,12,19,20]. Taking advantage of the unique reactivity shown by TCT, we have synthesized several s-triazine derivatives and evaluated their activity for several biological targets, which will be discussed in subsequent sections [13,14,[21][22][23][24][25][26][27][28]. TCT has been further explored as a linker that encompasses two key chemical concepts, namely orthogonality and chemoselectivity [8,16,29].…”

Section: Introductionmentioning

confidence: 99%

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s-Triazine: A Privileged Structure for Drug Discovery and Bioconjugation

et al. 2021

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This review provides an overview of the broad applicability of s-triazine. Our many years working with this intriguing moiety allow us to discuss its wide activity spectrum (inhibition against MAO-A and -B, anticancer/antiproliferative and antimicrobial activity, antibacterial activity against MDR clinical isolates, antileishmanial agent, and use as drug nano delivery system). Most of the compounds addressed in our studies and those performed by other groups contain only N-substitution. Exploiting the concept of orthogonal chemoselectivity, first described by our group, we have successfully incorporated different nucleophiles in different orders into s-triazine core for application in peptides/proteins at a temperature compatible with biological systems.

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Recent updates on 1,2,3‐, 1,2,4‐, and 1,3,5‐triazine hybrids (2017–present): The anticancer activity, structure–activity relationships, and mechanisms of action

Dong

Jiang

Zhang

et al. 2022

Archiv der Pharmazie

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Cancer is one of the leading causes of death across the world, and the prevalence and mortality rates of cancer will continue to grow. Chemotherapeutics play a critical role in cancer therapy, but drug resistance and side effects are major hurdles to effective treatment, evoking an immediate need for the discovery of new anticancer agents. Triazines including 1,2,3-, 1,2,4-, and 1,3,5-triazine have occupied a propitious place in drug design and development due to their excellent pharmacological profiles. Mechanistically, triazine derivatives could interfere with various signaling pathways to induce cancer cell death. Hence, triazine derivatives possess potential in vitro and in vivo efficacy against diverse cancers. In particular, triazine hybrids are able to overcome drug resistance and reduce side effects.Moreover, several triazine hybrids such as brivanib (indole-containing pyrrolo[2,1-f ][1,2,4]triazine), gedatolisib (1,3,5-triazine-urea hybrid), and enasidenib (1,3, 5-triazine-pyridine hybrid) have already been available in the market. Accordingly, triazine hybrids are useful scaffolds for the discovery of novel anticancer chemotherapeutics. This review focuses on the anticancer activity of 1,2,3-, 1,2, 4-, and 1,3,5-triazine hybrids, together with the structure-activity relationships and mechanisms of action developed from 2017 to the present. The enriched structure-activity relationships may be useful for further rational drug development of triazine hybrids as potential clinical candidates.

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Barbiturate- and Thiobarbituarte-Based s-Triazine Hydrazone Derivatives with Promising Antiproliferative Activities

Cited by 25 publications

References 40 publications

Synthesis, Anti-proliferative Activity, and Molecular Docking Study of New Series of 1,3-5-Triazine Schiff Base Derivatives

Synthesis, Anti-proliferative Activity, and Molecular Docking Study of New Series of 1,3-5-Triazine Schiff Base Derivatives

s-Triazine: A Privileged Structure for Drug Discovery and Bioconjugation

Recent updates on 1,2,3‐, 1,2,4‐, and 1,3,5‐triazine hybrids (2017–present): The anticancer activity, structure–activity relationships, and mechanisms of action

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