The Antiproliferative and Apoptotic Effect of a Novel Synthesized S-Triazine Dipeptide Series, and Toxicity Screening in Zebrafish Embryos

Abstract

Several derivatives containing morpholine/piperidine, anilines, and dipeptides as pending moieties were prepared using s-triazine as a scaffold. These compounds were evaluated for their anticancer activity against two human breast cancer cell lines (MCF-7 and MDA-MB-231), a colon cancer cell line (HCT-116), and a non-tumorigenic cell line (HEK 293). Tamoxifen was used as a reference. Animal toxicity tests were carried out in zebrafish embryos. Most of these compounds showed a higher activity against breast cancer than colon cancer. Compound 3a—which contains morpholine, aniline, and glycylglycinate methyl ester—showed a high level of cytotoxicity against MCF-7 cells with IC50 values of less than 1 µM. This compound showed a much lower level of toxicity against the non-tumorigenic HEK-293 cell line, and in the in vivo studies using zebrafish embryos. Furthermore, it induced cell cycle arrest at the G2/M phase, and apoptosis in MCF-7 cells. On the basis of our results, 3a emerges as a potential candidate for further development as a therapeutic drug to treat hormone receptor-positive breast cancer.

New star-shaped ligands generated by evolutionary fitting the Omicron spike inner-cavity

“…However, those starshaped molecules tend to be highly hydrophobic and toxic. With the progression of the new Omicron variants, star-shaped molecules reducing any possible toxicity of those triazine core derivatives [49][50][51][52] while preserving the cross docking to Omicron inner-cavity would be more desirable now.…”

Synthesis and Antiproliferative Activity of a New Series of Mono- and Bis(dimethylpyrazolyl)-s-triazine Derivatives Targeting EGFR/PI3K/AKT/mTOR Signaling Cascades

“…The widespread importance of the synthesis and modification of anticancer agents has given rise to many numbers of medicinal chemistry programs. In this regard, s -triazine derivatives have attracted attention due to their remarkable activity against a wide range of cancer cells. − Hexalen, also known as Altretamine (Figure , compound I ), which was first approved by the U.S. Food and Drug Administration (U.S. FDA) in 1990, is an example of an antineoplastic drug based on an s -triazine privileged structure, and it is used for the treatment of refractory ovarian cancer . Other examples of commercial drugs based on the s -triazine moiety include Enasidenib (Idhifa) (Figure , compound II ), which is used to treat IDH2-positive acute leukemia and was first approved by the U.S. FDA in 2017, and Gedatolisib (Figure , compound III ), a first-in-class PI3K/mTOR inhibitor used to treat breast cancer .…”

Recent Advances in the Biological Activity of s-Triazine Core Compounds

“…Moreover MCF-7 cells were significantly arrested in the G2/M stage. An in vivo studies of 34 in zebrafish presented non-toxic properties [21].…”

“…The role of the epidermal growth factor receptor (EGFR) in the pathogenesis proces is an important topic of scientific research. As a result, it was discovered that mutation leading to overexpression of EGFR genes (e.g., increased regulation or amplification) ar significantly associated with many cancers: lung granuloma (40% of cases), rectal tumors glioblastoma (50%), and epithelial carcinomas of the head and neck (80-100%) [21,22].…”