Identification, Synthesis, and Biological Evaluations of Potent Inhibitors Targeting Type I Protein Arginine Methyltransferases was written by Li, Xiao;Zhang, Lun;Xu, Jing;Liu, Chenyu;Zhang, Xiaojian;Abdelmoneim, Amr Abbas;Zhang, Qian;Ke, Jiaqi;Zhang, Yingnan;Wang, Lei;Yang, Fan;Luo, Cheng;Jin, Jia;Ye, Fei. And the article was included in Journal of Chemical Information and Modeling in 2022.Synthetic Route of C7H6Cl2O This article mentions the following:
CARM1 (coactivator-associated arginine methyltransferase 1), which belongs to type I PRMTs (protein arginine methyltransferases), is a potential therapeutic target for treatment of multiple cancers. In this study, we first identified several hit compounds against CARM1 by structure-based virtual screening (IC50 = 35.51 ± 6.68 to 68.70 ± 8.12 μM) and then carried out chem. structural optimizations, leading to six compounds with significantly improved activities targeting CARM1 (IC50 = 18 ± 2 to 107 ± 6 nM). As a compound with an ethylenediamino motif, the most potent inhibitor, ZL-28-6, also exhibited potent inhibition against other type I PRMTs. Compared to the type I PRMT inhibitor from our previous work (DCPR049_12), ZL-28-6 showed increased potency against CARM1 and decreased activity against other type I PRMTs. Moreover, ZL-28-6 showed better antiproliferation activities toward a series of solid tumor cells than DCPR049_12, indicating its broad spectrum of anticancer activity. In addition, cellular thermal shift and Western blot assays validated that ZL-28-6 could target CARM1 in cells. Taken together, the inhibitor we identified could serve as a potent probe for studying CARM1′s biol. functions and shed light on the future design of novel CARM1 inhibitors with stronger activities and selectivities. In the experiment, the researchers used many compounds, for example, (2,4-Dichlorophenyl)methanol (cas: 1777-82-8Synthetic Route of C7H6Cl2O).
(2,4-Dichlorophenyl)methanol (cas: 1777-82-8) belongs to alcohols. The oxygen atom of the strongly polarized O―H bond of an alcohol pulls electron density away from the hydrogen atom. This polarized hydrogen, which bears a partial positive charge, can form a hydrogen bond with a pair of nonbonding electrons on another oxygen atom. Tertiary alcohols cannot be oxidized at all without breaking carbon-carbon bonds, whereas primary alcohols can be oxidized to aldehydes or further oxidized to carboxylic acids.Synthetic Route of C7H6Cl2O
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts