Chemistry and Biological Activity of Coumarins at Molecular Level

Garro, Hugo Alejandro; García, Celina; Martı́n, Victor S.; Tonn, Carlos E.; Pungitore, Carlos Rodolfo

doi:10.1177/1934578x1400900808

Cited by 5 publications

(7 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among other natural polyphenolic compounds, this plant species contains coumarin derivatives with potential therapeutic effect [15]. For example, some coumarins inhibit the activity of vitamin K-dependent γ-carboxylase involved in the activation of coagulation factors [16]. Coumarins may inhibit platelet functions through multiple mechanisms including scavenging of reactive oxygen species, inhibiting cyclic nucleotide phosphodiesterase and prostaglandin syntheses [16].…”

Section: Discussionmentioning

confidence: 99%

Anticoagulant activity of some Artemisia dracunculus leaf extracts

et al. 2015

View full text Add to dashboard Cite

Platelet hyperactivity and platelet interaction with endothelial cells contribute to the development and progression of many cardiovascular diseases such as atherosclerosis and thrombosis. The impact of platelet activity with different pharmacological agents, such as acetylsalicylic acid and coumarin derivatives, has been shown to be effective in the prevention of cardiovascular disease. Artemisia dracunculus, L. Asteraceae (Tarragon) is used for centuries in the daily diet in many Middle Eastern countries, and it is well known for its anticoagulant activity. The present study investigates the presence of coumarins in tarragon leaves and subsequently determines the extract with a major amount of coumarin derivatives. The solvents of different polarities and different pH values were used for the purpose of purifying the primary extract in order to obtain fractions with the highest coumarin content. Those extracts and fractions were investigated for their anticoagulant activity by determining prothrombin time (PT) and the international normalized ratio (INR), expressed in relation to the coagulation time of the healthy person. Purified extracts and fractions obtained from plant residue after essential oil distillation, concentrated in coumarin derivatives, showed the best anticoagulant activity, using samples of human blood. INR maximum value (2.34) and consequently the best anticoagulant activity showed the methanol extract at concentration of 5%. The INR value of normal plasma in testing this extract was 1.05.

show abstract

Section: Discussionmentioning

confidence: 99%

Anticoagulant activity of some Artemisia dracunculus leaf extracts

et al. 2015

View full text Add to dashboard Cite

show abstract

“…The aromatic ring forms hydrophobic interaction with the carbon residues of the protein to destabilize the enzyme (Musa et al, 2008; Riveiro et al, 2010). Coumarins with long chain hydrocarbon substitution such as ostruthin, ammoresinol, anthogenol, novobiocin, coumermycin, and chartreusin demonstrate anti-bacterial activity on many gram positive and gram negative bacteria (Matos et al, 2012; Garro et al, 2014). Although none of the commercially available anti-TB drugs possess coumarin scaffold, scopoletin and umbelliferone are active against Mycobacterium tuberculosis H 37 Rv, with MIC values of 42 and 58.3 μg/mL, respectively (Rezayan et al, 2012; Upadhyay et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Mutation at G103 of MtbFtsZ Altered their Sensitivity to Coumarins

et al. 2017

View full text Add to dashboard Cite

Coumarins are natural polyphenol lactones comprising of fused rings of benzene and α-pyrone. The current study demonstrates the inhibitory effect of coumarins with various substitutions on Mycobacterium smegmatis mc2 155. We also demonstrate the effect of pomegranate (Punica granatum) extract containing ellagic acid, on M. smegmatis as well as their affect on MtbFtsZ (FtsZ from Mycobacterium tuberculosis). The ellagic acid extracts from pomegranate peels inhibit mycobacteria with a MIC of 25 μM and 0.3 to 3.5 mg/mL, respectively, but failed to inhibit the polymerization of MtbFtsZ. However, the coumarins were shown to inhibit the polymerization and GTPase activity of the protein as well as have an inhibitory affect on M. smegmatis mc2 155. Docking of the most active coumarin (7-Dimethyl-4-methyl coumarin with MIC of 38.7 μM) to the GTP binding site suggests that it interacted with the G103 residue. Based on the docking results two mutants of varying activity (G103S and G103A) were constructed to elucidate the interaction of MtbFtsZ and coumarins. Mutation of G103 with Serine (a bulky group) results in an inactive mutant and substitution with alanine produces a variant that retains most of the activity of the wild type. There is a disruption of the protofilament formation of the MtbFtsZ upon interaction with coumarins as demonstrated by TEM. The coumarins increase the length of Mycobacteria five times and MtbFtsZ localization is disturbed. The mutant proteins altered the GTPase and polymerization activity of coumarins as compared to wild type protein. The results here support that coumarins inhibit proliferation of Mycobacteria by targeting the assembly of MtbFtsZ and provide the possible binding site of coumarins on MtbFtsZ. This study may aid in the design of natural products as anti-mycobacterial agents. The currently reported GTP analogs for FtsZ are toxic to the human cell lines; natural coumarins targeting the GTP binding site of MtbFtsZ may hold promise as an important drug lead for tuberculosis treatment.

show abstract

“…Some reviews on involvement of coumarin nucleus as antitumor [56,57], anti-HIV [58] and anti-Alzheimer's diseases [59,60] are available in the literature. Some compilation reports on all activities associated with coumarin nucleus are also reported [61][62][63][64][65][66]. But so far no review available in the literature where coumarin nucleated molecules with their application exclusively as anti-TB agents in detail.…”

mentioning

confidence: 93%