Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
Department of Pharmaceutical Technology (Process Chemistry), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
Eur J Med Chem. 2021 Aug 5;220:113445. doi: 10.1016/j.ejmech.2021.113445. Epub 2021 Apr 20.
Hymenialdisine an alkaloid of oroidin class has drawn the attention of researchers owing to its unique structural features and interesting biological properties. Hymenialdisine exhibited promising inhibitory activity against a number of therapeutically important kinases viz., CDKs, GSK-3β etc., and showed anti-cancer, anti-inflammatory, anti-HIV, neuroprotective, anti-fouling, anti-plasmodium properties. Hymenialdisine and other structurally related oroidin alkaloids such as dibromo-hymenialdisine, stevensine, hymenin, axinohydantoin, spongicidines A-D, latonduines and callyspongisines contain pyrrolo[2,3-c] azepin-8-one core in common. Keeping in view of the interesting structural and therapeutic features of HMD, several structural modifications were carried around the fused-azepinone core which resulted in a number of diverse structural motifs like indolo-azepinones, paullones, aza-paullones, darpones and 5,7-dihydro-6H-benzo[b]pyrimido[4,5-d] azepin-6-one. In this review, an attempt is made to collate and review the structures of diverse hymenialdisine and related fused-azepinones of synthetic/natural origin and their biological properties.
由于其独特的结构特征和有趣的生物性质,海米那啶生物碱作为奥罗汀类的一种生物碱引起了研究人员的关注。海米那啶表现出对许多治疗上重要的激酶(如 CDK、GSK-3β 等)的有希望的抑制活性,并具有抗癌、抗炎、抗 HIV、神经保护、抗污损、抗疟原虫的特性。海米那啶和其他结构相关的奥罗汀生物碱,如二溴海米那啶、史蒂文斯碱、海米宁、阿克西诺酮、海绵二氢嘧啶 A-D、拉顿二酮和卡利海绵素,共同含有吡咯并[2,3-c]吖庚因-8-酮核心。鉴于 HMD 的有趣的结构和治疗特征,围绕稠合的吖庚因核心进行了几种结构修饰,得到了许多不同的结构基序,如吲哚吖庚因、保尔酮、氮杂保尔酮、达酮和 5,7-二氢-6H-苯并[b]嘧啶并[4,5-d]吖庚因-6-酮。在这篇综述中,我们试图整理和综述了合成/天然来源的不同海米那啶和相关稠合吖庚因的结构及其生物性质。