Coumarins as Emerging Anti-Viral Compounds from Natural Origins: Ethnopharmacology, Chemistry, Mechanism of Action, Clinical and Preclinical Studies, and Future Perspectives

From the natural origin, more than 1300 coumarins have already been recognized. Coumarins are natural products and secondary metabolites in plants, and they can be synthesized chemically. Coumarins are fused benzene and pyrone ring systems. Coumarin is a fragrant chemical that emits a distinctive odor. They are anti-viral compounds having anti-HIV, anti-dengue, anti-hepatitis, anti-influenza, and anti-chikungunya properties. Coumarins are classified into different classes. Pyranocoumarins are classified into two classes: first one is the angular type, and the second is the linear type. Moreover, angular-type pyranocoumarins show anti-viral activity; calanolide A, B, and F (+)-dihydrocalanolide A and B pseudocordatolide from inophyllum A, B, C, E, P, G1, and G2 are examples. Coumarins show other pharmacology activities like antitumor, cytotoxicity, antioxidant, antimalarial, anticancer, and anticoagulant. The pattern of substitution affects the pharmacological, biochemical, and therapeutic properties of simple coumarins. The anticoagulants warfarin and dicoumarol, aflatoxins, and psoralens are much more complex-related substances based on the coumarin nucleus. Calanolide A, calanolide B, (+)-12-oxo-calanolide A, and dihydrocalanolide B were tested in vitro in combination with NRTIs, NNRTIs, and PIs. They had different anti-viral synergistic or additive interactions with NRTIs, NNRTIs, and PIs. Coumarin derivatives have been synthesized using a variety of methods: Perkin reaction, Bachmann-Duisbery reaction, Pechmann reaction, and Kostanecki acylation of o-hydroxy ketones.