Coumarins antibacterial activity

Coumarins. - There is interest in the synthesis of 3-substituted coumarins cyclization of substituted salicylaldehydes with cyanoacetamide, followed by treatment with phosphoryl chloride in DMF, has given coumarin-3-carbonitriles. High yields of 3-phenylcoumarins were obtained when ortho-hydroxy-aldehydes or -ketones were treated with phenylacetyl chloride-potassium carbonate.When cyclohexane-1,3-diones (187) were condensed with triethyl orthoformate and either urea and thiourea and the initial product (188) was allowed to condense with nitriles, the 3-carboxamide (189) was obtained in good yield.The antibacterial activity of some sulphones has prompted the synthesis of 3-arylsulphonyl-coumarins by oxidation of sulphides. ... 

The antibacterial activity of a number of synthetic 3-acylamino-4-hydroxycoumarin derivatives [92] and of several other coumarins has been describe [93, 94]. However, as the carbamoyl group is of great importance to novobiocin activity, it may be that the activity of coumarin is not directly related to the activity of the antibiotic. 

Aminocoumarin antibiotics such as novobiocin, clorobiocin, and coumermycin A1 are derived from different Streptomyces species and show a very potent antibacterial activity by inhibition of DNA gyrase. Gyrase inhibitors block DNA replication, induce the SOS repair system, and eventually cause bacterial cell death (Figure 6.32) [151-154], These antibiotics possess a 3-amino-4-hydroxy-coumarin and a substituted deoxysugar noviose as common feature, which is essential for their biological activity. The biosynthetic gene clusters for novobiocin, chlorobiocin, and coumermycin A1 have been cloned in Streptomyces coelicolor M512 [155,156]. 

Since aminocoumarins have been found to exert some antibacterial activity [377], investigations were started to explore tuberculostatic activity of various coumarins related to p-aminosalicylic acid (55). 7-Amino-4-methylcoumarin (56) was found to be about one-half, and ffa s-p-aminocinnamic acid (57) one-fourth, as active as p-aminosalicylic acid [392]. The tuberculostatic action of 7-amino-4-methylcoumarin is probably dependent on the opening of the lactone... 

Recent synthetic coumarin anticoagulants also failed to support the dicou-marol theory, and even these new compounds rendered the role of 4-hydroxyl group doubtful. Derivatives of a single 4-hydroxycoumarin moiety with an aliphatic monocarboxylic acid or 4-methylcoumarin with diethylaminoethyl side chain showed some anticoagulant and antibacterial activities [418]. 

Ng TB, ling JM, Wang ZT, Cai JN, Xu GJ (1996) Examination of coumarins, flavonoids and polysaccharopeptide for antibacterial activity. Gen Pharmacol 27 1237—1240 Nowakowska Z (2007) A review of anti-infective and anti-inflammatory chalcones. Eur J Med Chem 42 125-137... 

Several coumarin derivatives have revealed pronounced medicinal value as antibacterial and antifungal agents [57,58]. Others have displayed antituber-cular activity [59] and some have insecticidal properties [60]. This prompted us to investigate the preparation of a new series of compounds containing coumarin moieties with different side chains or fused rings. 

The synthesis of 186 with a 3-thioamide substituent (93ZOR1465) succeeded. Several pyrano[3,2-c]coumarins 186 and their derivatives possessing promising antibacterial and fungicidal activity were also synthesized (01MOL519, 03MOF275). 

Rehman, S.U., Chohan, Z.H., Gulnaz, F. and Supuran, C.T. (2005) In-vitro antibacterial, antifungal and cytotoxic activities of some coumarins and their metal complexes. /. Enzyme Inhib. Med. Chem., 20,333-40. 

Particular attention has been paid to the antibacterial, antiviral, antiinflammatory and antifertility effects of Wikstroemia indica that contains abrmdant active constituents, including flavonoids, biflavonoids, coumarins, lignans, volatile oils, polysaccharides, etc. [66]... 

Erythromycin is a known inhibitor of the cytochrome P450 isoenzyme CYP3A4. However, this isoenzyme has only a minor role in the metabolism of warfarin , (p.358), specifically the less active R-isomer of warfarin. Consequently, only minor increases in the levels of warfarin have been seen in pharmacokinetic studies, which would generally not be expected to be clinically relevant. However, it is possible that even these small changes might be important in a very few patients, particularly those with a low prothrombin complex aetivity. Other macrolides (azithromycin, clarithromycin, dirithromycin, roxithromycin) have less effect on CYP3A4 than erythromycin, and consequently would be expected to have even less effect on the pharmacokinetics of warfarin or acenocoumarol, which is borne out in the few studies available. Nevertheless, cases of interactions have been reported for nearly all these macrolides. Moreover, one cohort study found that clarithromycin increased the risk of an interaction and erythromycin did not. It is possible that there is some other, as yet unidentified, mechanism involved. Alternatively, it is equally possible that the relatively few cases just represent idiosyncratic effects attributable to other factors, and not to any interaction (see also Coumarins -i- Antibacterials , p.365). 

These include the SSA-catalyzed synthesis of heterocyclic compounds such as xanthenes, coumarins, oxazoles, and so on. Xanthenes are of great therapeutic and biological interest on account of their many biological activities such as anti-inflanunatory, antiviral, antibacterial properties, and so on. Seyyed Hamzeh et al. (2008) carried out the SSA-catalyzed synthesis of aryl-14 f-dibenzo[fl,y]xanthenes from aldehydes and P-naphthol and 1,8-dioxo-octahydro-xanthenes from aldehydes and 1,3-dicarbonyl componnd such as dimedone under solvent-free conditions (Schemes 5.25, 5.26). Reactions were carried out at 80°C. Nazeruddin et al. (2011) documented an effective method for 9,10-dihydro-12-aryl-8 f-benzo[a]xanthenes-ll(12 f)-one derivatives in excellent yield and short reaction time using SSA under solvent-free conditions (Scheme 5.27). 

Rosselli S, Maggio A, Bellone G, Formisano C, Basile A, Cicala C, Alfieri A, Mascolo N, Bruno M (2007) Antibacterial and anticoagulant activities of coumarins isolated from the flowers of Magydaris tomentosa. Planta Med 73 116... 

In this review we have discussed published results concerning the QSAR research on antimicrobial properties of synthetic and natural compounds. Antifungal and antimicrobial activity of some coumarin derivatives, various types of biological activities of benzamides, several studies on cinnamic acid derivatives with antibacterial and antifungal activity, reports on the biological activity of homoisoflavanones and phenolic compounds, as well as pharmaceutical applications of furan derivatives have been shown. 

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