Coumarins and Coumarin-Related Compounds in Pharmacotherapy of Cancer

Abstract

Cancer is one of the most common causes of disease-related deaths worldwide. Despite the discovery of many chemotherapeutic drugs that inhibit uncontrolled cell division processes for the treatment of various cancers, serious side effects of these drugs are a crucial disadvantage. In addition, multi-drug resistance is another important problem in anticancer treatment. Due to problems such as cytotoxicity and drug resistance, many investigations are being conducted to discover and develop effective anticancer drugs. In recent years, researchers have focused on the anticancer activity coumarins, due to their high biological activity and low toxicity. Coumarins are commonly used in the treatment of prostate cancer, renal cell carcinoma and leukemia, and they also have the ability to counteract the side effects caused by radiotherapy. Both natural and synthetic coumarin derivatives draw attention due to their photochemotherapy and therapeutic applications in cancer. In this review, a compilation of various research reports on coumarins with anticancer activity and investigation and a review of structure-activity relationship studies on coumarin core are presented. Determination of important structural features around the coumarin core may help researchers to design and develop new analogues with a strong anticancer effect and reduce the potential side effects of existing therapeutics.

Synergy, Additivity, and Antagonism between Cisplatin and Selected Coumarins in Human Melanoma Cells

“…Naturally occurring coumarins are the largest group of benzopyrone derivatives (1,2-benzopyrones or 2 H -1-benzopyran-2-ones), widespread in plant species belonging to various families, including Apiaceae, Rutaceae , Asteraceae , Fabaceae , Oleaceae , Moraceae , and Thymelaeaceae [ 23 ]. These compounds are classified into different groups: simple coumarins such as osthole (OST), furanocoumarins (e.g., xanthotoxin (XIN), xanthotoxol (XOL), isopimpinellin (ISO), and imperatorin (IMP)— Figure 1 ), pyranocoumarins (e.g., visnadin, xanthyletin, and seselin), dicoumarins, and pyrone-substituted coumarins, such as alternariol, gravelliferone, coumestrol, warfarin, dicumarol, and novobiocin [ 24 ].…”

Trending Topics on Coumarin and Its Derivatives in 2020

“…The activity of coumarins as anticancer agents is at the top of reviews published in 2020 [ 5 , 6 , 7 , 8 ], as well as research papers. Potent inhibitors ( Figure 2 , general structure I ) of aldo–keto reductase (AKR) presenting an iminocoumarin scaffold, with activities between 25 and 56 nM, have been described for the treatment of prostatic cancer [ 9 ].…”

Coumarin Derivatives in Inflammatory Bowel Disease

“…Coumarins are categorized into four main subtype classes of compounds: simple coumarins, furanocoumarins, pyranocoumarins, and the pyrone-substituted coumarins. Simple coumarins are composed of molecules with hydroxyl, alkoxyl, and alkyl substitution patterns on the basic structure and their glucosides [ 11 ]. Simple coumarin class represents the main class of coumarin derivatives with intestinal anti-inflammatory properties, particularly esculetin, esculin, 4-hydroxycoumarin, osthole, and 4-methylesculetin ( Figure 2 ).…”

“…Furanocoumarins are composed of coumarins derivatives in which a furan ring is fused with the basic structure of coumarin via C6-C7 or C7-C8 [ 10 , 11 ], generating linear furanocoumarins (fusion via C6-C7) such as psolaren, imperatorin, and xanthotoxin or angular furanocoumarins (fusion via C7-C8) such as isobergapten and angelicin ( Figure 3 ). Similarly, in the pyranocoumarins, a six-membered pyran ring is fused with the benzene ring of the basic structure of coumarins via C6-C7 or C7-C8 [ 10 , 11 ]. Decursin (a linear pyranocoumarin) and seselin (an angular pyranocoumarin) are some examples of pyranocoumarins ( Figure 3 ), which have no intestinal anti-inflammatory activity.…”

“…Finally, pyrone-substituted coumarins are coumarin derivatives containing different chemical radicals fused with the pyran ring of coumarin [ 10 , 11 ]. Pyrone-substituted coumarins include natural and synthetic coumarins such as warfarin and dicoumarol ( Figure 3 ).…”