Design and Synthesis of New Thiophene/Thieno[2,3-d]pyrimidines along with Their Cytotoxic Biological Evaluation as Tyrosine Kinase Inhibitors in Addition to Their Apoptotic and Autophagic Induction was written by Elmongy, Elshaymaa I.;Attallah, Nashwah G. M.;Altwaijry, Najla;AlKahtani, Manal Mubarak;Henidi, Hanan Ali. And the article was included in Molecules in 2022.Synthetic Route of C7H12N2O This article mentions the following:
This work describes the synthesis and anticancer activity against kinase enzymes of newly designed thiophene and thieno[2,3-d]pyrimidines I [R = 2-(2-chloroacetyl)hydrazino, (3-methyl-2,5-dioxo-pyrrol-1-yl)amino, 2-[2-[(5-tert-butylisoxazol-3-yl)amino]acetyl]hydrazino, etc.] and II [R1 = Cl, (5-tert-butylisoxazol-3-yl)amino, (3-tert-butylisoxazol-5-yl)amino] along with their potential to activate autophagic and apoptotic cell death in cancer cells. The designed compounds were scanned for their affinity for kinases. The results were promising with affinity ranges from 46.7% to 13.3%. Mol. docking studies were performed, and the compounds were then screened for their antiproliferative effects. Interestingly, compounds I [R = 2-(2-chloroacetyl)hydrazino, (3-methyl-2,5-dioxo-pyrrol-1-yl)amino] resulted in higher cytotoxic effects than the reference standard against MCF-7 and HepG-2. The compounds were evaluated for their induction of apoptosis and/or necrosis on HT-29 and HepG-2. Three compounds induced significant early apoptosis compared to untreated control HT-29 cells, and four derivatives were more significant compared to untreated HepG-2 cells. Further investigated the effect of four compounds on the autophagy process within HT-29, HepG-2, and MCF-7 cells with flow cytometry. Similar to the apoptosis results, I [R = 2-(2-chloroacetyl)hydrazino] showed the highest autophagic induction among all compounds The potential inhibitory activity of the synthesized compounds on kinases was assessed. Screened compounds showed inhibition activity ranging from 41.4% to 83.5%. Compounds recorded significant inhibition were further investigated for their specific FLT3 kinase inhibitory activity. Noticeably, I [R = 2-(2-chloroacetyl)hydrazino] exhibited the highest inhibitory activity against FLT3. In the experiment, the researchers used many compounds, for example, 3-(tert-Butyl)isoxazol-5-amine (cas: 59669-59-9Synthetic Route of C7H12N2O).
3-(tert-Butyl)isoxazol-5-amine (cas: 59669-59-9) belongs to isoxazole derivatives. Isoxazoles also form the basis for a number of drugs, including the COX-2 inhibitor valdecoxib (Bextra) and a neurotransmitter agonist AMPA. The electrophilic cyclization of various 2-alkynone O-methyl oximes with a wide range of substrates such as ICl, I2, Br2, PhSeBr, etc. provides a variety of 3,4,5-trisubstituted isoxazoles in good to excellent yields.Synthetic Route of C7H12N2O
Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem