ee ‘Send Orders for Reprints to reprints@benthamscience.ae Curren Topics in Medicinal Chemist, 18 18, 12448 REVIEW ARTICLE Coumarin Compounds in Medicinal Chemistry: Some Important Exam- ples from the Last Years ‘Thiago Moreira Pereira, Daiana Portella Franco, Felipe Vitorio, and Arthur Eugen Kiimmerle” Laboratério de Diversidade Molecular e Quimica Medicinal (LaDMol-OM, Molecular Diversity and Medicinal Chemis- try Laboratory), Departament of Chemistry, Universidade Federal Rural do Rio de Janeiro, Seropédica, Rio de Janeiro, 239897-000, Brazil Abstract: Coumarins are natural products characterized as 1,2 benzopyrones wilely distibuted in plans, as well as, in many species of fungi and bacteria. Nowadays, many synthetic procedures allow the discovery of coumarins with expanded chemical space. The ability to exert noncovalent interactions with many enzymes and receptors in live organisms lead the coumarins to exhibit a wide range of bio logical activities and applications, Then, this manuscript provides an overview of the use of coumarins ‘compounds in medicinal chemistry in treating many diseases. Important examples of the lst years have been selected concerning the activities of coumarins as anticoagulant, anticancer, antioxidant, antiviral, anti-diabetis,ant-nflammatory, antibacterial, antifungal and ani-neurodegerative agents. Additional it also includes applications of coumarins as Nuorescent sensors for biological systems. Thus, this work ‘ims to contribute to the development of new rational research projects forthe teatment and diagnosis ‘of pathologies using coumarin derivatives. ‘cp ora 18 Keywords: Coumarins, biological activity, fluorescent sensors, structure-activity relationship, fungi, enzymes. 1. INTRODUCTION Coumarins are organic heterocycles characterized as 1,2 benzopyrones (1, Fig. 1) and comprise a group of natural products found in a wide range of plants [1]. Coumarin was first isolated by Vogel in 1820 from dipteryx odorata, popu- larly known as cumaru. After this first report, many works ‘were published demonstrating the isolation and synthesis of ‘coumarins and analogues from other species (2). Fig. (1). Chemical structure ofthe coumarin, Coumarins are an important class of secondary metabo- lites widely distributed and found in several parts of plants, such as roots, lowers and fruits. Plants with much divers fied habits are able to biosynthesize coumarins, such as tree shrubs and herbs [3] More than 1300 coumarins were identified from natural sources, mainly green plants [4]. However, the biosynthesis ‘of coumarins are not restricted to plants, and some species of “Adare comeipondence ty his autor at he Labor de Drerade Molecule e Quimica Medicinal (LaDMO/-QM, Molecular Diversity and ‘Medicinal Chemisty Laboratory), Departament of Chemistry, Universidade Feder Rural do Rio de Tanci, Serpéis, Rio de Janeiro, 239897-000, ‘Brazil Ema: kummere@hotmailcom 1873429418 358.007.00 fungi (Armillariella tabescens, Fomitopsis officinalis) and bacteria (Streptomyces niveus, Escherichia coli), are also able to biosynthesize coumarins [5]. ‘The main pathway of coumarin biosynthesis occurs by shikimic acid route, via cinnamic acid, through phenyla- Janine metabotism. In this pathway, L-phenylalanine und ‘goes deamination by phenylalanine ammonium lyase (PAL), producing trans-cinnamic acid (6, Then, orto/para hydroxy- lation of ans-cinnamic acid is carried out by the enzymes cinnamate 2'-hydroxylase and cinnamate 4’-hydroxylase, which generate 2-,4- and 2,4-hydroxycinnamic acids, respec- tively [5,7]. After hydroxylation, cinnamic acids undergo EVZ isomerization, followed by lactonization [5]. From this biosynthesis, umbelliferone, esculetin and scopoletin, the ‘most common coumarins derivatives found in nature, are obtained [7], Coumarins are important to plant physiology, acting as antioxidants and enzymatic inhibitors. This class. of sub- stances is involved in the control of plant growth, respira- tion, photosynthesis and defense against infections [1]. The interesting biological properties of coumarins have led to the development of organic synthesis process [8], which allowed to obtain known coumarin compounds at a larger scale as well as new derivatives with biological and industrial pur- poses. ‘The synthesis of coumarins began in the mid-nineteenth ‘century with the discovery of the famous condensation be- tween salicylaldehyde and acetic anhydride by Perkin [9] (© 2018 Bentham Scence Publishers