Advances in Spirocyclic Hybrids: Chemistry and Medicinal Actions

Title:Advances in Spirocyclic Hybrids: Chemistry and Medicinal Actions

Volume: 25 Issue: 31

Author(s): Mohammed Benabdallah*, Oualid Talhi*, Fatiha Nouali, Nouredine Choukchou-Braham, Khaldoun Bachari and Artur M.S. Silva*

Affiliation:

• Laboratoire de Catalyse et Synthese en Chimie Organique, Faculté des Sciences, Universite de Tlemcen, BP 119, 13000 Tlemcen,Algeria

• Centre de Recherche Scientifique et Technique en Analyses Physico- Chimiques CRAPC, BP 384, Bou-Ismail-RP 42004, Tipaza,Algeria

• QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro,Portugal

Keywords: Spirocyclic compounds, heterocycles, hybrids, synthesis, biological activities, drug design, anticancer, inhibitory effects.

Abstract: 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.

Cite this article as:

Benabdallah Mohammed *, Talhi Oualid *, Nouali Fatiha , Choukchou-Braham Nouredine , Bachari Khaldoun and Silva M.S. Artur *, Advances in Spirocyclic Hybrids: Chemistry and Medicinal Actions, Current Medicinal Chemistry 2018; 25 (31) . https://dx.doi.org/10.2174/0929867325666180309124821