ABSTRACT
Unique plants and their properties, once considered synonymous to medicine, remain a potent source for new compounds in modern science. Plant polyphenols and natural products continue to be investigated for effective treatments for the most persistent of human ailments. In this review, fifty novel plant phenolic compounds have been compiled and briefly described from the previous five years. Select compounds and notable plant species from genus Morinda and Sophora are further expanded on. Traditional medicine plants often contain rich and diverse mixtures of flavonoids, from which rare compounds should receive attention. The bioactivity of crude plant extracts, purified compounds and mixtures can differ greatly, requiring that these interactions and mechanisms of action be investigated in greater detail. Novel applications of uncommon natural products, namely mimosine and juglone, are explored within this review. The 2019 coronavirus pandemic has resulted in abrupt spike of related scientific publications: speculation is made regarding plant natural products and future of antiviral drug discovery.
ABSTRACT
Juglans regia Linn. is a valuable medicinal plant that possesses the therapeutic potential to treat a wide range of diseases in humans. It has been known to have significant nutritional and curative properties since ancient times, and almost all parts of this plant have been utilized to cure numerous fungal and bacterial disorders. The separation and identification of the active ingredients in J. regia as well as the testing of those active compounds for pharmacological properties are currently of great interest. Recently, the naphthoquinones extracted from walnut have been observed to inhibit the enzymes essential for viral protein synthesis in the SARS-CoV-2. Anticancer characteristics have been observed in the synthetic triazole analogue derivatives of juglone, and the unique modifications in the parent derivative of juglone have paved the way for further synthetic research in this area. Though there are some research articles available on the pharmacological importance of J. regia, a comprehensive review article to summarize these findings is still required. The current review, therefore, abridges the most recent scientific findings about antimicrobial, antioxidant, anti-fungal, and anticancer properties of various discovered and separated chemical compounds from different solvents and different parts of J. regia.
ABSTRACT
SARS-CoV-2 as a positive-sense single-stranded RNA coronavirus caused the global outbreak of COVID-19. The main protease (Mpro) of the virus as the major enzyme processing viral polyproteins contributed to the replication and transcription of SARS-CoV-2 in host cells, and has been characterized as an attractive target in drug discovery. Herein, a set of 1,4-naphthoquinones with juglone skeleton were prepared and evaluated for the inhibitory efficacy against SARS-CoV-2 Mpro. More than half of the tested naphthoquinones could effectively inhibit the target enzyme with an inhibition rate of more than 90% at the concentration of 10 µM. In the structure-activity relationships (SARs) analysis, the characteristics of substituents and their position on juglone core scaffold were recognized as key ingredients for enzyme inhibitory activity. The most active compound, 2-acetyl-8-methoxy-1,4-naphthoquinone (15), which exhibited much higher potency in enzyme inhibitions than shikonin as the positive control, displayed an IC50 value of 72.07 ± 4.84 nM towards Mpro-mediated hydrolysis of the fluorescently labeled peptide. It fit well into the active site cavity of the enzyme by forming hydrogen bonds with adjacent amino acid residues in molecular docking studies. The results from in vitro antiviral activity evaluation demonstrated that the most potent Mpro inhibitor could significantly suppress the replication of SARS-CoV-2 in Vero E6 cells within the low micromolar concentrations, with its EC50 value of about 4.55 µM. It was non-toxic towards the host Vero E6 cells under tested concentrations. The present research work implied that juglone skeleton could be a primary template for the development of potent Mpro inhibitors.