Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Menoufia University, Egypt.
Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt.
Future Med Chem. 2024 Apr;16(7):601-622. doi: 10.4155/fmc-2023-0336. Epub 2024 Mar 4.
The purpose of this work is to create and synthesize a new class of chemicals: 3-cyano-2-substituted pyridine compounds with expected multitarget inhibition of histone deacetylase (HDAC) and tubulin. The target compounds ( and ) were synthesized utilizing 6-(4-methoxyphenyl)-2-oxo-4-(3,4,5-trimethoxyphenyl)-3-cyanopyridine, with various linkers and zinc-binding groups (ZBGs). Most of the tested compounds showed promising growth inhibition, and hydroxamic acid-containing hybrids possessed higher HDAC inhibition than other ZBGs. Compound possessed the highest potency; however, it showed the most tubulin polymerization inhibition. Docking studies displayed good binding into HDAC1 and six pockets and tubulin polymerization protein. Compound could be considered a good antitumor candidate to go further into and clinical studies.
3-氰基-2-取代吡啶化合物，预期具有组蛋白去乙酰化酶（HDAC）和微管蛋白的多靶点抑制作用。目标化合物（和）是利用 6-（4-甲氧基苯基）-2-氧代-4-（3,4,5-三甲氧基苯基）-3-氰基吡啶，通过各种连接子和锌结合基团（ZBG）合成的。大多数测试的化合物表现出有希望的生长抑制作用，含羟肟酸的杂化物具有比其他 ZBG 更高的 HDAC 抑制作用。化合物 具有最高的效力；然而，它表现出最高的微管蛋白聚合抑制作用。对接研究显示与 HDAC1 和六个口袋以及微管蛋白聚合蛋白有良好的结合。化合物 可以被认为是一个很好的抗肿瘤候选物，以进一步进行和临床研究。
