Impact of Traditional Plants and their Secondary Metabolites in the Discovery of COVID-19 Treatment.

BACKGROUND: Coronavirus Disease-2019 belongs to the family of viruses which cause serious pneumonia along with fever, breathing issues and infection of lungs, and was first reported in China and later spread worldwide. OBJECTIVE: Several studies and clinical trials have been conducted to identify potential drugs and vaccines for Coronavirus Disease-2019. The present study listed natural secondary metabolites identified from plant sources with antiviral properties and could be a safer and tolerable treatment for Coronavirus Disease-2019. METHODS: A comprehensive search on the reported studies was conducted using different search engines such as Google Scholar, SciFinder, Sciencedirect, Medline PubMed, and Scopus for the collection of research articles based on plant-derived secondary metabolites, herbal extracts, and traditional medicine for coronavirus infections. RESULTS: Status of COVID-19 worldwide and information of important molecular targets involved in COVID- 19 are described, and through literature search, it is highlighted that numerous plant species and their extracts possess antiviral properties and are studied with respect to coronavirus treatments. Chemical information, plant source, test system type with a mechanism of action for each secondary metabolite are also mentioned in this review paper. CONCLUSION: The present review has listed plants that have presented antiviral potential in the previous coronavirus pandemics and their secondary metabolites, which could be significant for the development of novel and a safer drug which could prevent and cure coronavirus infection worldwide.

Hispolon: A natural polyphenol and emerging cancer killer by multiple cellular signaling pathways.

Nature as an infinite treasure of chemotypes and pharmacophores will continue to play an imperative role in the drug discovery. Natural products (NPs) such as plant and fungal metabolites have emerged as leads in drug discovery during recent years due to their efficacy, safety and selectivity. The current review summarizes natural sources as well as pharmacological potential of hispolon which is a major constituent of traditional medicinal mushroom Phellinus linteus. The study aims to update the scientific community about recent developments of hispolon in the arena of natural drugs by providing insights into its present status in therapeutic pursuits. Hispolon, a polyphenol has been reported to possess anticancer, antidiabetic, antioxidant, antiviral and anti-inflammatory activities. It fights against cancer via induction of apoptosis, halting cell cycle and inhibition of metastasis by targeting various cellular signaling pathways including PI3K/Akt, MAPK and NF-κB. The current review proposes that hispolon provides a novel opportunity for pharmacological applications and its styrylpyrone carbon skeleton might serve as an attractive scaffold for drug development. However, future researches are recommended to assess bioavailability, toxicological limits, pharmacokinetic and pharmacodynamic profiles of hispolon, in order to establish its potential as a potent multi-targeted drug in the near future.

Synthesis, evaluation of thymidine phosphorylase and angiogenic inhibitory potential of ciprofloxacin analogues: Repositioning of ciprofloxacin from antibiotic to future anticancer drugs.

Over expression of thymidine phosphorylase (TP) in various human tumors compared to normal healthy tissue is associated with progression of cancer and proliferation. The 2-deoxy-d-ribose is the final product of thymidine phosphorylase (TP) catalyzed reaction. Both TP and 2-deoxy-d-ribose are known to promote unwanted angiogenesis in cancerous cells. Discovery of potent inhibitors of thymidine phosphorylase (TP) can offer appropriate approach in cancer treatment. A series of ciprofloxacin 2, 3a-3c, 4a-4d, 5a-5b, 6 and 7 has been synthesized and characterized using spectroscopic techniques. Afterwards, inhibitory potential of synthesized ciprofloxacin 2, 3a-3c, 4a-4d, 5a-5b, 6 and 7 against thymidine phosphorylase enzyme was assessed. Out of these twelve analogs of ciprofloxacin nine analogues 3a-3c, 4a-4c, 5a-5b and 6 showed good inhibitory activity against thymidine phosphorylase. Inhibitory activity as presented by their IC50 values was found in the range of 39.71 ± 1.13 to 161.89 ± 0.95 µM. The 7-deazaxanthine was used as a standard inhibitor with IC50 = 37.82 ± 0.93 µM. Furthermore, the chick chorionic allantoic membrane (CAM) assay was used to investigate anti-angiogenic activity of the most active ciprofloxacin-based inhibitor 3b. To enlighten the important binding interactions of ciprofloxacin derivatives with target enzyme, the structure activity relationship and molecular docking studies of chosen ciprofloxacin analogues was discussed. Docking studies revealed key π-π stacking, π-cation and hydrogen bonding interactions of ciprofloxacin analogues with active site residues of thymidine phosphorylase enzyme.

Biochanin A: A novel bioactive multifunctional compound from nature.

Natural products (NPs) will continue to serve humans as matchless source of novel drug leads and an inspiration for the synthesis of non-natural drugs. As our scientific understanding of 'nature' is rapidly expanding, it would be worthwhile to illuminate the pharmacological distinctions of NPs to the scientific community and the public. Flavonoids have long fascinated scientists with their remarkable structural diversity as well as biological functions. Consequently, this review aims to shed light on the sources and pharmacological significance of a dietary isoflavone, biochanin A, which has been recently emerged as a multitargeted and multifunctional guardian of human health. Biochanin A possesses anti-inflammatory, anticancer, neuroprotective, antioxidant, anti-microbial, and hepatoprotective properties. It combats cancer development by inducing apoptosis, inhibition of metastasis and arresting cell cycle via targeting several deregulated signaling pathways of cancer. It fights inflammation by blocking the expression and activity of pro-inflammatory cytokines via modulation of NF-κB and MAPKs. Biochanin A acts as a neuroprotective agent by inhibiting microglial activation and apoptosis of neurons. As biochanin A has potential to modulate several biological networks, thus, it can be anticipated that this therapeutically potent compound might serve as a novel lead for drug development in the near future.

Salvianolic acid A & B: potential cytotoxic polyphenols in battle against cancer via targeting multiple signaling pathways.

Nature has generously offered life-saving therapies to mankind by providing evolutionarily optimized drug-like entities in the form of natural products. These splendid gifts of nature have served as most suitable candidates for anti-cancer drug discovery due to their pleiotropic activity on target molecules. This review aims to provide an update on the natural sources and bioactivities of such gifts from nature, salvianolic acid A & B, which are major bioactive constituents of a traditional Chinses medicinal herb, Salvia miltiorrhiza. Salvianolic acid A & B have been reported to owe anti-cancer, anti-inflammatory and cardioprotective activities. Currently salvianolic acids have been emerged as potent anti-cancer molecules. Salvianolic acid A & B fight cancer progression by prompting apoptosis, halting cell cycle and adjourning metastasis by targeting multiple deregulated signaling networks of cancer. Moreover, salvianolic acid A & B display potency towards sensitizing cancer cells to chemo-drugs. The review purposes that salvianolic acid A & B supply a novel opportunity for drug discovery but further experimentation is mandatory to embellish the knowledge of their pharmacological usage and to access their toxicological limits in order to establish these compounds as potential multitarget future drugs.