PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES

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1 PHARMA SCIENCE MNITR AN INTERNATINAL JURNAL F PHARMACEUTICAL SCIENCES FURANNE DERIVATIVES: DIVERSE BILGICAL ACTIVITIES Sachin Singh*, Pramod Kumar Sharma, Nitin Kumar, Rupesh Dudhe Department of armaceutical Technology, Meerut Institute of Engineering and Technology, Meerut ABSTRACT From a last decade heterocyclic compounds are playing an important role in medicinal chemistry. Article is based on the different pharmacological aspects of the furanone ring, from a last decade a lot of work is going on, on the furanones, scientists develop a lots of new compounds related to this moiety and screened them for there different pharmacological activities to get a molecule which have good pharmacological activity and lesser side effect. Heterocyclic compounds having, N, S atoms shows various pharmacological activities. Furanones are hetrocyclic compounds containing oxygen atom in their ring structure, having various pharmacological activities like antiinflammatory, anticancer, antibacterial, and antiviral, antioxidant activity. In this review we have attempted to compile various biological activities of furanone derivatives. Keywords: Anti-inflammatory activity, Furanone, Antioxidant, Antiviral activity. INTRDUCTIN Furanone (Fig.1) is a heterocyclic compound containing two oxygen atoms in five membered ring systems. It is a natural product synthesized by biochemical pathways in plants of the genus Angelica. Furanone is also known as g-crotonolactone or β-angelica lactone [1]. Furanone moieties have been incorporated into a wide variety of therapeutically interesting drug candidates such as Penicillic acid [2] (Fig. 2) and Basidalin [3] (Fig. 3) are butenolide natural products [4] shows antitumour activity in the smaller range. Butalactin (Fig. 4) is another example of epoxide side chain containing antibiotic having Furanone ring as basic moiety [5]. The novel furanone antibiotics such as aminofuranones correspond to Narthogenin bioisosteres [6] ( Fig. 5) where the methoxy group present at C3 position was replaced by amino groups [7]. Furanone derivatives shows different biological activities such as antibacterial, antifungal, antiviral, anticancer, anti-tubercular, anti- inflammatory and thus can be used as a lead in the discovery of new drug molecule. IC VALUE 4.01 S - 51

2 The various substituted furanones have been synthesized that posses various pharmacological activities against so many microorganisms. Furanone is a colourless liquid, natural products synthesized by biochemical pathways, especially plants of the genus Angelica, hence it is called as β-angelica lactone. It is the simplest butenolide thus it is called "butenolide" in the context of natural product synthesis. Me NH 2 H Figure 1 Figure 2 Figure 3 H H 3 C H H Figure 4 Figure 5 Anti-inflammatory and analgesic activity: M. M. Alam et al 2009 synthesized a series of 3-arylidene-5-(4-chloro-phenyl)- 2(3h)-furanones and evaluated for their anti-inflammatory activity. ut of the 11 synthesized compounds, compound (a) and (b) (Fig. 6) showed higher degree of antiinflammatory activity [8]. R X Compound X R 6 a NCH 2 C 6 H b NCH 2 C 6 H 5 4-F Figure 6 IC VALUE 4.01 S - 52

3 Two series of new furanones, which was substituted by methylsulfonylphenyl or methylsulfamidophenyl moieties were synthesized by V. Weber et al 2005 and found to protect against oxidation damage in vitro experiments. Two compounds 1 and 2 (Fig. 7) showed potent anti-inflammatory activity [9]. R 2 R 1 H Compound R 1 R 2 1 S 2 CH 3 H 2 S 2 CH 3 CH 2 CH 2 CH 2 CH 2 H Figure 7 C. K. Lau et al 1999 synthesized a series of 3-heteroaryloxy-4-phenyl-2-(5H)- furanones and evaluated for their potency and selectivity as CX-2 inhibitors. Compound 3-(5-bromopyridin-2-yloxy)-5, 5-dimethyl-4-(4-(methylsulfonyl) phenyl) furan-2(5h)- one (Fig. 8) found to be potent selective CX-2 inhibitors [10]. S 2 CH 3 H 3 C CH 3 N Figure 8 Antioxidant activity: A series of 4, 5-diaryl-3-hydroxy-2(5H)-furanones were synthesized by F. Bailly et al 2008 and evaluated for their antioxidant potencies. Compound 3-hydroxy-5-(3,4- IC VALUE 4.01 S - 53 Br

4 dihydroxyphenyl)-4-(4-hydroxyphenyl)furan-2(5h)-one (Fig. 9) showed potent antioxidant activity [11]. H H H H Figure 9 Pascal Couderta et al 2005 synthesized two series of new furanones substituted by methylsulfonylphenyl or methylsulfamidophenyl moieties and evaluated their anti oxidants and anti-inflammatory activity. Compound 3-hydroxy-5-(4-hydroxyphenyl)-4- (4-(methylsulfonyl) phenyl) furan-2(5h)-one (Fig.10) and 5-(4-chlorophenyl)-4-hydroxy- 3-(hydroxyphenyl) furan-2(5h)-one (Fig.11) shows more potent activity [12]. H H 3 C 2 S H H H Figure 10 Figure 11 V. Weber et al 2002 synthesized a series of thirteen novels 4, 5-diaryl-3-hydroxy- 2(5H)-furanones with various substitutions patterns and screened their antioxidant activity. Compound 3-hydroxy-5-(3, 4-dihydroxyphenyl)-4-phenylfuran-2(5H)-one (Fig.12) showed the most powerful antioxidant activity [13]. IC VALUE 4.01 S - 54

5 H H H H Figure 12 Anti-viral activity: A series of 3-(1, 3-diphenylpyrazol-4-yl-methylene)-5-aryl-2(3H)-furanones were synthesized A.I. Hashem et al 2007 and screened them for antiviral activity against HAV virus. Compound (3E)-5-(4-chlorophenyl)-3-((1,3-diphenyl-1H-pyrazol-4yl) methylene) furan-2(3h)-one(fig.13) showed highest activity against HAV(Hepatitis A Verena) virus [14]. H N N Figure 13 D. Iannazzo et al 2008 synthesized a series of 3-amino-2(5H)furanones compound and evaluated for there antiviral activity. In this series compound (Fig. 14) produce more potent. This compound able to block the replication of subgenomic HCV RNA in liver cells [15]. IC VALUE 4.01 S - 55

6 MeHN C()NH Me Figure 14 F. Bailly et al 2008 synthesized a series of 4, 5-diaryl-3-hydroxy-2(5H)-furanones compound. Compound with a 4-hydroxyphenyl group on position 4(Fig. 15) compounds were found to be moderate inhibitors of HIV-1 integrase activity [16]. R H H R= 3,4-diH-C 6 H 4 Figure 15 Anti-bacterial activity: E. Gondela et al 2010 synthesized a series of derivatives of (3,4-dichloro-5- hydroxy-2(5h)-furanone and screened for their antibacterial activity. ut of these substituted furanone series, compound (Fig. 16) exhibited potent antibacterial activity [17]. NHCH 2 CHHCH 2 H Figure 16 Anti-bacterial and anti-protozoal activities: Eric Lattmann et al 2005 synthesized a series of 5-hydroxy-2(5H)-furanones derivatives and tested for antibacterial activity. Compounds 3-chloro-5-hydroxy-4- IC VALUE 4.01 S - 56

7 (methylamino) furan-2(5h)-one (Fig.17) and 3-chloro-5-hydroxy-4-(phenylamino) furan- 2(5H)-one (Fig. 18) showed potent antibacterial activity [18]. CH 3 HN HN H H Figure 17 Figure 18 5-(u-Hydroxyalkylamino) derivatives of mucochloric acids was synthesized by E. Gondela (2010) et al using 3, 4-dichloro-5-hydroxy-2(5H)-furanone (mucochloric acid) (Fig. 19) acetate or 5-methylcarbonate which undergo facile substitution with suitable amino alcohol and were characterized for antibacterial and antiprotozoal activities [19]. H Figure 19 Anti-cancer activity: F. Bailly et al 2008 synthesized a series of thirteen 4, 5-diaryl-3-hydroxy-2(5H)- furanones and evaluated for their PC 3 cell proliferation by MTT method (Malignant triton tumor).compound 3-hydroxy-5-(3, 5-dihydroxyphenyl)-4-(4-hydroxyphenyl) furan- 2(5H)-one (Fig. 20) showed potent anticancer activity among the other derivatives [20]. IC VALUE 4.01 S - 57

8 H H H H Figure 20 J. P. Rappai et al 2009 was synthesized a series of two tri aryl-3(2h) - furanones and their antitumor activity was evaluated. These 2 compounds 2, 3-dihydro-3-oxo-2, 4, 5-triphenylfuran-2-yl acetate (Fig. 21) and 2-methoxy-2, 4, 5-triphenylfuran-3(2H)-one (Fig. 22) significantly reduced the proliferation of DLA cells [21]. CCH 3 CH 3 Figure 21 Figure 22 Anti-fungal activity: A series of racemic 3-phenyl-5-methyl-2H, 5H-furan-2-ones which are supposed to be related to natural product, (-)Incrustoporine, were synthesized by M. Pour et al 2000 and their antifungal activity were determined. The compound 3-(3,4- dichlorophenyl)-5-methylfuran-2(5h)-one (Fig. 23) showed potent antifungal activity, against filamentous fungi Absidia corymbifera [22]. Figure 23 IC VALUE 4.01 S - 58

9 P. Senel et al 2010 synthesized a series of 5-Acetoxymethyl-3-(4-bromophenyl)- 2, 5-dihydrofuran-2-one derivatives and evaluated for antifungal activity. Compound 3- (4-bromophenyl)-5-methylenefuran-2(5H)-one (Fig. 24) showed highest activity against Candida albicans and Candida glabrata [23]. Br CH 2 Figure 24 CNCLUSIN Furanone is a unique template that is associated with several biological activities. This article high lightened research work of many researchers reported in literature for different pharmacological activities on furanone compounds synthesized. The review has presented comprehensive details on furanone analogues, potent compounds reported for particular pharmacological activity and the method or technique involved in evaluation process. More investigations must be carried out to evaluate more activities of furanone for many diseases whose treatment are difficult in the medical sciences. REFERENCES 1. Flematti GR, Ghisalberti EL, Dixon KW and Trengove RD: Science ; 5686: Black D K J: Synthesis and antibacterial activities of 5-hydroxy-4-amino-2(5H)- furanones. Chemical Society of Japan 1966; 23: Hiyama T, ishi H, Nishide K and Saimoto H: Bull.Synthesis and antibacterial activities of 5-hydroxy-4-amino-2(5H)-furanone. Chemical Society of Japan1987; 60: Coombs J,Lattmann E and Hoffmann H M R:Synthesis and antibacterial activities of 5-hydroxy-4-amino-2(5H)-furanones. Bioorganic & Medicinal Chemistry 1998; Franco CM, Borde UP, Chatterjee S, Bulmbach J, Synthesis and antibacterial activities of 5-hydroxy-4-amino-2(5H)-furanones, Ganguli, B. N. J. Antibiotics.Bioorganic Medicinal Chemistry 1991; 44: IC VALUE 4.01 S - 59

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