Tassopoulou Vassiliki-Panagiota, Tzara Ariadni, Kourounakis Angeliki P
Department of Medicinal Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, 15771, Athens, Greece.
ChemMedChem. 2022 Dec 5;17(23):e202200320. doi: 10.1002/cmdc.202200320. Epub 2022 Oct 26.
Multifactorial diseases exhibit a complex pathophysiology with several factors contributing to their pathogenesis and development. Examples of such disorders are neurodegenerative (e. g. Alzheimer's, Parkinson's) and cardiovascular diseases (e. g. atherosclerosis, metabolic syndrome, diabetes II). Traditional therapeutic approaches with single-target drugs have been proven, in many cases, unsatisfactory for the treatment of multifactorial diseases such as diabetes II. The well-established by now strategy of multitarget drugs is constantly gaining interest and momentum, as a more effective approach. The development of pharmacomolecules able to simultaneously modulate multiple relevant-to-the-disease targets has already several successful examples in various fields and has, as such, inspired the design of multitarget antidiabetic agents; this review highlights the design aspect and efficacy of this approach for improved antidiabetics by presenting several examples of successful pharmacophore combinations in (multitarget) agents that modulate two or more molecular targets involved in diabetes II, resulting in a superior antihyperglycemic profile.
多因素疾病表现出复杂的病理生理学，有多种因素促成其发病机制和发展。这类疾病的例子包括神经退行性疾病（如阿尔茨海默病、帕金森病）和心血管疾病（如动脉粥样硬化、代谢综合征、II型糖尿病）。在许多情况下，已证明使用单靶点药物的传统治疗方法对于治疗多因素疾病（如II型糖尿病）并不令人满意。作为一种更有效的方法，目前成熟的多靶点药物策略正不断获得关注并发展壮大。能够同时调节多个与疾病相关靶点的药物分子的开发在各个领域已有多个成功实例，因此激发了多靶点抗糖尿病药物的设计；本综述通过展示（多靶点）药物中成功的药效团组合的几个例子，突出了这种方法在改进抗糖尿病药物方面的设计要点和疗效，这些药物组合可调节II型糖尿病中涉及的两个或更多分子靶点，从而产生更优的抗高血糖作用。
