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.

Lawsonia inermis Linn. (Lythraceae) or henna has been used since the earliest times as a medicine, preservative, and cosmetic. It has long been recommended in traditional medicine as an astringent, purgative, and abortifacient. Lawsone and six extracts of L. inermis plant, used by Algerian traditional healers to treat infectious diseases, were screened for their antifungal activity against filamentous fungi. Water and five organic extracts - DMSO, ethanol, chloroform, ethyl acetate, and di-ethyl ether - of L. inermis leaves, collected in the area of Adrar (Algeria), were prepared by soaking 25 g of powdered plant in 100 mL of solvent. The extracts were screened for antifungal activity using the poisoned food technique against five filamentous fungi. Results demonstrated that the best yield (8.03%) was obtained with the ethanol extract. The commercial lawsone showed potentially interesting MICs against the strains Fusarium oxysporum (12 µg/mL) and Aspergillus flavus (50 µg/mL). The ethanol extract showed the only interesting MIC (230 µg/mL of crude extract) against the strain F. oxysporum compared with other extracts. These results suggest that the Algerian L. inermis plant has antifungal activity that can be related to the presence of lawsone in the leaves plant. The results can be exploited largely in research of new antifungal drugs.