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Recent updates on 1,2,3-, 1,2,4-, and 1,3,5-triazine hybrids (2017-present): The anticancer activity,
Gaoli Dong1, Yingchun Jiang2, Feng Zhang1
1School of Chemistry and Pharmaceutical Engineering, Huanghuai University, Zhumadian, China.
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.
Insights
Triazine hybrids show promise as novel anticancer agents, overcoming drug resistance and reducing side effects. This review explores their anticancer activity, structure-activity relationships, and mechanisms of action.
Area of Science:
- Medicinal Chemistry
- Oncology
- Drug Discovery
Background:
- Cancer remains a leading global cause of death, with increasing prevalence and mortality.
- Chemotherapeutics face challenges from drug resistance and side effects, necessitating new anticancer agents.
- Triazine derivatives offer excellent pharmacological profiles and are valuable in drug design.
Purpose of the Study:
- To review the anticancer activity of 1,2,3-, 1,2,4-, and 1,3,5-triazine hybrids.
- To analyze structure-activity relationships (SAR) and mechanisms of action (MoA) of triazine hybrids.
- To highlight the potential of triazine scaffolds for developing novel chemotherapeutics.
Main Methods:
- Literature review of studies from 2017 to the present.
- Analysis of in vitro and in vivo efficacy data for various triazine derivatives.
- Examination of SAR and MoA for different triazine hybrid structures.
Main Results:
- Triazine derivatives demonstrate efficacy against diverse cancers by interfering with signaling pathways.
- Triazine hybrids show potential to overcome drug resistance and mitigate side effects.
- Several marketed drugs (e.g., brivanib, gedatolisib, enasidenib) are based on triazine scaffolds.
Conclusions:
- Triazine hybrids are effective scaffolds for developing novel anticancer drugs.
- Understanding SAR and MoA can guide rational drug development of triazine-based therapies.
- Triazine hybrids hold significant potential as future clinical candidates for cancer treatment.
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