College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Korea.
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Molecules. 2021 Jan 21;26(3):553. doi: 10.3390/molecules26030553.
Pathological angiogenesis is a hallmark of cancer; accordingly, a number of anticancer FDA-approved drugs act by inhibiting angiogenesis via different mechanisms. However, the development process of the most potent anti-angiogenics has met various hurdles including redundancy, multiplicity, and development of compensatory mechanisms by which blood vessels are remodeled. Moreover, identification of broad-spectrum anti-angiogenesis targets is proved to be required to enhance the efficacy of the anti-angiogenesis drugs. In this perspective, a proper understanding of the structure activity relationship (SAR) of the recent anti-angiogenics is required. Various anti-angiogenic classes have been developed over the years; among them, the heterocyclic organic compounds come to the fore as the most promising, with several drugs approved by the FDA. In this review, we discuss the structure-activity relationship of some promising potent heterocyclic anti-angiogenic leads. For each lead, a molecular modelling was also carried out in order to correlate its SAR and specificity to the active site. Furthermore, an in silico pharmacokinetics study for some representative leads was presented. Summarizing, new insights for further improvement for each lead have been reviewed.
病理性血管生成是癌症的一个标志；因此，许多经美国食品和药物管理局批准的抗癌药物通过不同的机制抑制血管生成来发挥作用。然而，大多数强效抗血管生成药物的开发过程遇到了各种障碍，包括冗余、多样性以及通过血管重塑来开发补偿机制。此外，事实证明，需要鉴定广谱抗血管生成靶点，以提高抗血管生成药物的疗效。在这方面，需要正确了解最近的抗血管生成药物的构效关系（SAR）。多年来已经开发了各种抗血管生成药物类别；其中，杂环有机化合物作为最有前途的药物脱颖而出，有几种药物已获得美国食品和药物管理局的批准。在这篇综述中，我们讨论了一些有前途的强效杂环抗血管生成先导化合物的构效关系。对于每个先导化合物，还进行了分子建模，以将其 SAR 和特异性与活性部位相关联。此外，还介绍了一些代表性先导化合物的计算机药代动力学研究。总之，对每个先导化合物的进一步改进提出了新的见解。
