Eldehna, Wagdy M.; El Hassab, Mahmoud A.; Abo-Ashour, Mahmoud F.; Al-Warhi, Tarfah; Elaasser, Mahmoud M.; Safwat, Nesreen A.; Suliman, Howayda; Ahmed, Marwa F.; Al-Rashood, Sara T.; Abdel-Aziz, Hatem A.; El-Haggar, Radwan published an article in 2021. The article was titled 《Development of isatin-thiazolo[3,2-a]benzimidazole hybrids as novel CDK2 inhibitors with potent in vitro apoptotic anti-proliferative activity: Synthesis, biological and molecular dynamics investigations》, and you may find the article in Bioorganic Chemistry.HPLC of Formula: 17201-43-3 The information in the text is summarized as follows:
The present work aims at developing a new set of small mols. featuring the privileged isatin scaffold conjugated with a thiazolo[3,2-a]benzimidazole (TBI) motif through a cleavable hydrazide linker I (R = H, F, Br, OMe and NO2) and II (R = H, Br; R1 = Me, allyl, Bn, etc.) as potential anticancer CDK2 inhibitors. The growth of the two examined cell lines was significantly inhibited by most the prepared hybrids with IC50 ranges; (2.60 +/- 1.47-20.90 +/- 1.17μM, against MDA-MB-231) and (1.27 +/- 0.06-16.83 +/- 0.95μM, against MCF-7). They exerted a significance alteration in the cell cycle progression, in addition to an apoptosis induction within both MDA-MB-231 and MCF-7 cells. Furthermore, I (R = H), I (R = OMe) and II (R = H; R1 = Me) displayed potent CDK2 inhibitory action (IC50 = 96.46 +/- 5.3, 26.24 +/- 1.4 and 42.95 +/- 2.3 nM, resp.). Interestingly, the most potent CDK2 inhibitor I (R = OMe) achieved the best binding score (-11.2 Kcal/mol) and formed the most stable complex with CDK2 enzyme (RMSD = 1.24 Å ) in a 100 ns MD simulation. In addition, the MM-PBSA calculations ascribed the lowest binding free energy to the I (R = OMe)-CDK2 complex (-323.69 +/- 15.17 kJ/mol). Finally, these results suggested hybrid I (R = OMe) as a good candidate for further optimization as promising breast cancer antitumor agent and CDK2 inhibitor. The experimental process involved the reaction of 4-Cyanobenzyl bromide(cas: 17201-43-3HPLC of Formula: 17201-43-3)
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.HPLC of Formula: 17201-43-3
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts