The author of 《Enhancement of the tail hydrophobic interactions within the carbonic anhydrase IX active site via structural extension: design and synthesis of novel N-substituted isatins-SLC-0111 hybrids as carbonic anhydrase inhibitor and antitumor agent》 were Eldehna, Wagdy M.; Abo-Ashour, Mahmoud F.; Nocentini, Alessio; El-Haggar, Radwan S.; Bua, Silvia; Bonardi, Alessandro; Al-Rashood, Sara T.; Hassan, Ghada S.; Gratteri, Paola; Abdel-Aziz, Hatem A.; Supuran, Claudiu T.. And the article was published in European Journal of Medicinal Chemistry in 2019. Formula: C8H6BrN The author mentioned the following in the article:
Herein we report the design and synthesis of novel N-substituted isatins-SLC-0111 hybrids. A structural extension approach was adopted via N-alkylation and N-benzylation of isatin moiety to enhance the tail hydrophobic interactions within the carbonic anhydrase (CA) IX active site. Thereafter, a hybrid pharmacophore approach was utilized via merging the pharmacophoric elements of isatin and SLC-0111 in a single chem. framework. As planned, a substantial improvement of inhibitory profile of the target hybrids (KIs: 4.7-86.1 nM) towards hCA IX in comparison to N-unsubstituted leads (KIs: 192-239 nM), was achieved. Mol. docking of the designed hybrids in CA IX active site unveiled, as planned, the ability of N-alkylated and N-benzylated isatin moieties to accommodate in a wide hydrophobic pocket formed by T73, P75, P76, L91, L123 and A128, establishing strong van der Waals interactions. Hybrid I displayed good anti-proliferative activity under hypoxic conditions towards breast cancer MDA-MB-231 and MCF-7 cell lines (IC50 = 7.43 ± 0.28 and 12.90 ± 0.34 μM, resp.). Also, I disrupted the MDA-MB-231 cell cycle via alteration of the Sub-G1 phase and arrest of G2-M stage. Addnl., I displayed significant increase in the percent of annexinV-FITC pos. apoptotic cells from 1.03 to 18.54%. Furthermore, I displayed potent VEGFR-2 inhibitory activity (IC50 = 260.64 nM). Collectively, these data suggest I as a promising lead mol. for the development of effective anticancer agents. In the experimental materials used by the author, we found 4-Cyanobenzyl bromide(cas: 17201-43-3Formula: C8H6BrN)
4-Cyanobenzyl bromide(cas: 17201-43-3) is an important intermediate for pharmaceutical production. It can be used for the synthesis of a series of piperidine-linked aromatic diimidazolines, which have been synthesized as conformationally restricted congeners of the anti-Pneumocystis carinii (PCP) drug, Pentamidine.Formula: C8H6BrN
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts