Department of Physical Chemistry, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Kurpinskiego 5, 85-096 Bydgoszcz, Poland.
Faculty of Chemical Technology and Engineering, Bydgoszcz University of Science and Technology, Seminaryjna 3, 85-326 Bydgoszcz, Poland.
Int J Mol Sci. 2022 Jul 21;23(14):8046. doi: 10.3390/ijms23148046.
Tumors are still one of the main causes of death; therefore, the search for new therapeutic agents that will enable the implementation of effective treatment is a significant challenge for modern pharmacy. One of the important factors contributing to the development of neoplastic diseases is the overexpression of enzymes responsible for the regulation of cell division processes such as cyclin-dependent kinases. Numerous studies and examples of already-developed drugs confirm that isatin is a convenient basis for the development of new groups of inhibitors for this class of enzyme. Therefore, in this work, a new group of potential inhibitors of the CDK2 enzyme, utilizing isatin derivatives and substituted benzoylhydrazines, has been designed based on the application of computational chemistry methods, such as docking and molecular dynamics, and their inhibiting ability was assessed. In the cases of the selected compounds, a synthesis method was developed, and the selected physicochemical properties of the newly synthesized derivatives were estimated. As part of the completed project, new compounds are developed which are potential inhibitors of the CDK2 enzyme.
肿瘤仍然是主要死亡原因之一；因此，寻找新的治疗药物，以实现有效的治疗，是现代药学的重大挑战。导致肿瘤性疾病发展的一个重要因素是负责调节细胞分裂过程的酶（如细胞周期蛋白依赖性激酶）的过度表达。大量的研究和已经开发的药物的实例证实，靛红是开发此类酶新抑制剂的一个便利基础。因此，在这项工作中，基于计算化学方法（如对接和分子动力学），设计了一组利用靛红衍生物和取代苯甲酰肼的新型潜在 CDK2 酶抑制剂，并评估了它们的抑制能力。对于所选化合物，开发了一种合成方法，并估计了新合成衍生物的选定物理化学性质。作为已完成项目的一部分，开发了新的化合物，这些化合物是 CDK2 酶的潜在抑制剂。
