Title:Advances in Spirocyclic Hybrids: Chemistry and Medicinal Actions
Volume: 25
Issue: 31
关键词:
螺环化合物，杂环，杂合物，合成，生物活性，药物设计，抗癌，抑制作用。
摘要: The present review deals with the progress in medicinal chemistry of spirocyclic
compounds, a wider class of natural and synthetic organic molecules, defined as a hybrid of
two molecular entities covalently linked via a unique tetrahedral carbon. This spiro central
carbon confers to the molecules a tridimensional structurally oriented framework, which is
found in many medicinally relevant compounds, a well-known example is the antihypertensive
spironolactone. Various bioactive natural products possess the privileged spiro
linkage and different chemo-types thereof become synthetically accessible since the 20th century.
Actually, there has been a growing interest in the synthesis of heterocyclic hybrids gathered
via a spiro carbon. Most of these combinations are two moieties in one scaffold being
able to interfere with biological systems through sequential mechanisms. Spirocyclic hybrids
containing indole or oxindole units are compounds exhibiting higher interaction with biological
receptors by protein inhibition or enzymatic pathways and their recognition as promising
anticancer agents in targeted chemotherapy is foreseen. These specific, low-weight and noncomplex
spirocyclic hybrids are potent inhibitors of SIRT1, Mdm2–p53 and PLK4, showing
affinity for anaplastic lymphoma kinase (ALK) receptor. They are also known as excellent
DNA binders, acting on cellular division by arresting the cell cycle at different phases and inducing
apoptotic cell death. A structural diversity of spirocyclic hybrids has proved neuroprotective
effects, anti-HIV, antiviral and antibacterial activities. Hundred of papers are mentioned
in this review underlying chemical issues and pharmacological potencies of spiro compounds,
which render them impressive synthetic hits for innovative drug conception.
