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

Abstract

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.

Design, Synthesis, Docking Studies and Molecular Dynamics Simulation of New 1,3,5‐Triazine Derivatives as Anticancer Agents Selectively Targeting Pancreatic Adenocarcinoma (Capan‐1)

“…Thus, triazine hybrids serve as valuable beneficial templates in the development of novel drugs for cancer therapy. Recently, Dong, Yu et al [46] have reviewed extensively the anticancer activity of 1,2,3-, 1,2,4-, and 1,3,5triazine hybrids, together with the structure-activity relationships and mechanisms of action developed from 2017 to the present.…”

Isoxazolyl-Derived 1,4-Dihydroazolo[5,1-c][1,2,4]Triazines: Synthesis and Photochemical Properties

“…1,2,4-Triazine-based compounds and their fused congeners have anticancer, antimicrobial, antifungal, anti-inflammatory, antimalarial, and antiviral properties [ 1 , 2 , 3 , 4 ]. Since 1,2,4-triazines fused with five-membered heterocycles are considered bio-isosteres with a purine core, these derivatives are the focus of drug design [ 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. However, 1,2,4-triazines possessing specific photophysical properties have seldom been used in optoelectrical research.…”

Peculiarities of the Spatial and Electronic Structure of 2-Aryl-1,2,3-Triazol-5-Carboxylic Acids and Their Salts on the Basis of Spectral Studies and DFT Calculations

“…Due to this ability, triazoles are being widely tested for different biological activities, as well as for the synthesis of hybrid structures with drugs to enhance their binding to cellular receptors [ 3 ]. This fact allows the potential use of these compounds in medicinal chemistry [ 4 , 5 , 6 , 7 , 8 ].…”