Synthesis and structure-activity relationship of coumarins as potent Mcl-1 inhibitors for cancer treatment was written by Xia, Yang-Liu;Wang, Jing-Jing;Li, Shi-Yang;Liu, Yong;Gonzalez, Frank J.;Wang, Ping;Ge, Guang-Bo. And the article was included in Bioorganic & Medicinal Chemistry in 2021.Formula: C6H5ClO2 The following contents are mentioned in the article:
In this study, more than thirty coumarin derivatives I (R1 = H, NO2; R2 = Me, CF3, Ph, etc.; R3 = H, CH2NMe2, CH2N(CH2)4CHOH; R4 = OH, OMe, Cl, etc.; R5 = H, OH, OMe; R6 = H, OH, NO2, etc.) with different substituents were designed and synthesized, and their Mcl-1 inhibitory activities evaluated using a fluorescence polarization-based binding assay. The results showed that the catechol group was a key constituent for Mcl-1 inhibitory activity of the coumarins, and methylation of the catechol group led to decreased inhibitory activity. The introduction of a hydrophobic electron-withdrawing group at the C-4 position of 6,7-dihydroxycoumarin, enhanced Mcl-1 inhibitory capacity, and a hydrophilic group in this position was unbeneficial to the inhibitory potency. Among all coumarins tested, I (R1 = H; R2 = CF3; R3 = H; R4 = OH; R5 = OH; R6 = H) displayed the most potent inhibitory activity towards Mcl-1 (Ki = 0.21 ± 0.02μM, IC50 = 1.21 ± 0.56μM, resp.), for which the beneficial effect on taxol resistance was also validated in A549 cells. A strong interaction between I (R1 = H; R2 = CF3; R3 = H; R4 = OH; R5 = OH; R6 = H) and Mcl-1 in docking simulations further supported the observed potent Mcl-1 inhibition ability of I (R1 = H; R2 = CF3; R3 = H; R4 = OH; R5 = OH; R6 = H). 3D-QSAR anal. of all tested coumarin derivatives further provides new insights into the relationships linking the inhibitory effects on Mcl-1 and the steric-electrostatic properties of coumarins. This study involved multiple reactions and reactants, such as 4-Chlororesorcinol (cas: 95-88-5Formula: C6H5ClO2).
4-Chlororesorcinol (cas: 95-88-5) belongs to organic chlorides. Organic chlorides can cause corrosion in pipelines, valves and condensers, and cause catalyst poisoning. The hydrocarbon processing industry (HPI) and others are affected by damage caused by these substances. Alkyl chlorides are versatile building blocks in organic chemistry. While alkyl bromides and iodides are more reactive, alkyl chlorides tend to be less expensive and more readily available.Formula: C6H5ClO2
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics