Coumarins also known as benzopyran ones are

Coumarins also known as benzopyran-2-ones are a family of nature-occurring lactones first isolated from Tonka beans in 1820. They are an important class of oxygen containing heterocycles widely found in nature, so much so that they have been routinely employed as herbal remedies since early days. Over 1300 coumarins have been identified, principally as secondary metabolites in green plants, fungi and bacteria [4], this aspect however has motivated researchers all around the globe to identify and isolate these molecules for their extensive biological properties biological activities. Ever since the first synthesis reported in 1882, this moiety has found its place in certain perfumes, fabric conditioners and in pharmaceutical industry especially as anticoagulants viz. dicoumarol and warfarin, several such naturally occurring coumarins moieties have been reported (Fig. 2). Furthermore, several synthetic coumarins with a variety of pharmacophoric groups at C-3, C-4 and C-7 positions have been intensively screened for various biological properties. Over the past two decades there has been considerable amount of work with coumarins being tested for anti-microbial [5], [6], anti- HIV [7], [8], anti-cancer [9], [10], [11], [12], [13], [14], anti-tumor [15], [16], [17], anti-oxidant [18], [19], anti-coagulation activities [20], anti-retroviral [21], anti-pyretic, antinociceptive, anti-tuberculosis [22], acetyl choline inhibitors [23], anti-inflammatory [24] and DNA Gyrase inhibitors [25]. Recent literature survey suggests quite a few coumarin derivatives that have been patented for their biological properties [26] (Fig. 3). Due to the severe existing side effects of COX-inhibitors, there is an urgent need to find newer drug molecules that could act as effective PS-341 manufacturer and analgesic while reducing side effects such as cardiac problems. A number of different of heterocylic scaffolds are being tested for their anti-inflammation properties. Coumarin and its derivatives being available widely in nature has been rising prospect, lately a number of workers have had it in their sights and have focused their efforts in this direction, recently a review has been published on coumarin scaffolds used for anti-inflammation properties [27]. Here, we make a comprehensive effort to cover coumarins that have been reported to act as COX-inhibitors.
Coumarins derived from natural sources The advances in extraction and purification methods of natural compounds has accelerated the study of natural products by leaps and bounds [28]. Various biological active coumarins such as sesquiterpene coumarins [29], [30], furocoumarins [31] have been isolated from several plant sources and have been studied for a wide variety of biological properties [6], [18], [32], [33], [34], [35], [36], [37], [38], [39], [40]. The structures of all the naturally occurring coumarin reported in this review are represented in Fig. 4, Fig. 5, Fig. 6, Fig. 7, Fig. 8. Zaman et al. studies in vitro immunomodulatory and anti-inflammatory properties of terpenoid coumarins isolated from Ferula szowitsiana, medicinally important plants from Apiaceae family on immune cells isolated from naive mice and to elucidate possible underlying mechanisms of action. With splenocytes, effects of the agents on PHA-induced proliferation and interleukin (IL)-4 and interferon (IFN)-γ release were assessed. With peritoneal macrophages, anti-inflammatory potentials were evaluated in lipopolysaccharide (LPS)/IFNγ-stimulated cells via measures of changes in nitric oxide (NO) and PGE2 secretion. Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were determined via Western blot anal. The results showed that umbelliprenin (UMB) 1 and Me galbanate (MG) 2 reduced remarkably PHA-induced splenocyte proliferation and both preferentially induced TH2 IL-4 and suppressed TH1 IFNγ secretion, meanwhile considerably suppressing LPS-induced production. of NO and PGE2, leading to reductions in inducible iNOS and COX- expression. The authors believe study is the first of its kind to report on anti-inflammatory and immunomodulatory effects of UMB and MG in vitro [41].