SYNTHESIS OF BISCOUMARIN DERIVATIVES AS ANTIMICROBIAL AGENTS
Keywords:Benzylidene-bis-(4-hydroxycoumarin), benzopyranocoumarin derivatives, antibacterial assays, antifungal activity
Objective: As a further part of our chemical and biological studies in this field, we describe the preparations of the properly substituted benzylidene-bis-(4-hydroxycoumarin) derivatives 5a-h and 3-(6-oxo-(1H)-benzopyrano[4,3-b]benzopyran-7-yl)-4-hydroxycoumarin derivatives 6a-e.
Methods: The synthesized compounds were screened for their in vitro antimicrobial activity against five strains of bacteria and two fungal strains using disk diffusion assay and dilution method. The way in which the substituent group's physicochemical properties influence the antimicrobial activity is discussed in the paper.
Results: The in vitro evaluation of their inhibitory properties towards five strains of Gram-positive and Gram-negative bacteria and two fungal strains indicated that the Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â 4-trifluoromethylbenzylidene derivative of bis-(4-hydroxycoumarin) (compound 5c) and Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â 3-(6-oxo-(1H)-18-bromobenzopyrano[4,3-b]benzopyran-7-yl)-4-hydroxycoumarin derivative (compound 6b) possess the most potent antibacterial activities, with MIC of 3.9 Î¼g/mL - 7.8 Î¼g/mL against Gram-positive bacteria.
Conclusion: The compound 6b has greater antibacterial activity than the standard chloramfenicol (inhibition zone 26 mm and MIC 1.9 Î¼g/mL) against Staphyloccocus aureus and could be considered as leading compound in the future antimicrobial drug development.
Key words: Benzylidene-bis-(4-hydroxycoumarin), benzopyranocoumarin derivatives, antibacterial assays,Â antifungal activity.
Tenover FC. Mechanisms of antimicrobial resistance in bacteria. Am. J. Med. 2006; 34:64-73.
Butsch WL, Stewart JD. Administration of dicoumarin compound for prophylaxis of postoperative thrombosis and embolism. Arch. Surg. 1942; 45(4):551-553.
Manolov I, Maichle-Moessmer C, Nicolova I, Danchev N. Synthesis and anticoagulant activities of substituted 2,4-diketochromans, biscoumarins and chromanocoumarins. Arch. Pharm. 2006; 339(6):319-326.
Kostova I, Momekov G. New zirconium (IV) complexes of coumarins with cytotoxic activity. Eur. J. Med. Chem. 2006; 41(6):717-726.
Musaa AM, Khanb FO, Cooperwoodc JS. Synthesis and antiproliferative activity of coumarin-estrogen conjugates against breast cancer cell lines. Lett. Drug Des. Discov. 2009; 6(2):133-138.
Ghate M, Kusanur RA, Kulkarni MV. Synthesis and in vivo analgesic and anti-inflammatory activity of some bi heterocyclic coumarin derivatives. Eur. J. Med. Chem. 2005; 40:882-887.
Al-Ayed AS. Synthesis of new substituted chromen[4,3-c]pyrazol-4-ones and their antioxidant activities. Molecules. 2011; 16:10292-10302.
ZavrÅ¡nik D, MuratoviÄ‡ S, Makuc D, Plavec J, Cetina M, Nagl A. et al. Benzylidene-bis-(4-hydroxycoumarin) and benzopyranocoumarin derivatives: synthesis, 1H/13C-NMR conformational and X-ray crystal structure studies and in vitro antiviral activity evaluations. Molecules. 2011; 16:6023-6040.
Su CX, Mouscadet JF, Chiang CC, Tsai HJ, Hsu LY. HIV-1 Integrase Inhibition of Biscoumarin Analogues. Chem. Pharm. Bull. 2006; 54(5):682-686.
Hamdi N, Puerta MC, Valerga P. Synthesis, structure, antimicrobial and antioxidant investigations of dicoumarol and related compounds. Eur. J. Med. Chem. 2008; 43 (11):2541-2548.
Singh I, Kaur H, Kumar S, Kumar A, Lata S, Kumar A. Synthesis of new coumarin derivatives as antibacterial agents. Int. J. Chem. Tech. Res. 2010; 2(3):1745-1752.
Smyth T, Ramachandran VN, Smyth WF. A study of the antimicrobial activity of selected naturally occurring and synthetic coumarins. Int. J. Antimicrob. Agents. 2009; 33(5):421-426.
ZavrÅ¡nik D, MuratoviÄ‡ S, Å pirtoviÄ‡ S, SoftiÄ‡ DÅ¾, MediÄ‡-Å ariÄ‡ M. The synthesis and antimicrobial activity of 4-hydroxycoumarin derivatives. Bosn. J. Basic Med. Sci. 2008; 8(3):277-281.
Kayser O, Kolodziey H. Antibacterial activity of simple coumarins: structural requirements for biological activity. Z. Naturforch C. 1999; 54(3-4):169-174.
MladenoviÄ‡ M, VukoviÄ‡ N, Sukdolak S, SolujiÄ‡ S. Design of Novel 4-Hydroxy-chromene-2-one derivatives as antimicrobial agents. Molecules. 2010; 15(6):4294-4308.
El-Masry SL, Aly EI, Halem MA. New coumarin derivatives as antibacterial agents. Egypt J. Pharm. Sci. 1992; 33:379-390.
Lawson DM, Stevenson CE. Structural and functional dissection of aminocoumarin antibiotic biosynthesis: a review. J Struct Funct Genomics 2012; 13(2):125-33.
Galm U, Heller S, Shapiro S, Page M, Li SM, Heide L. Antimicrobial and DNA gyrase-inhibitory activities of novel clorobiocin derivatives produced by mutasynthesis. Antimicrob Agents and Chemother 2004; 48(4):1307-1312.
Musicki B, Periers AM, Laurin P, Ferroud D, Benedetti Y, Lachaud S et al. Improved antibacterial activities of coumarin antibiotics bearing 5â€™,5â€™-dialkylnoviose: biological activity of RU79115. Bioor. Med. Chem. Lett. 2000; 10(15):1695-1699.
Lafitte D, Lamour V, Tsvetkov PO, Makarov AA, Klich M, Deprez P et al. DNA gyrase interaction with coumarin-based inhibitors: the role of the hydroxybenzoate isopentenyl moiety and the 5'-methyl group of the noviose. Biochemistry. 2002; 41(23):7217-7223.
El Shaaer HM. Cyclocondensation, antimicrobial activity and semi-empirical AM1-MO calculations of benzopyrone derivatives. Eur. J. Med. Chem. 2012; 3(1): 51-56.
Trendafilova N, Mihaylov T. Molecular structure and reactive sites of substituted di-(4-hydroxycoumarin)s derived from DFT calculations. Internet Electron. J. Mol. Des. 2005; 4(8):591-602.
Smart BE. Fluorine substituent effects (on bioactivity). J. Fluor. Chem. 2001; 109(1): 3-11.
Dipankar B, Panneerselvam P, Asish B. Synthesis, characterization and antimicrobial activities of some 2-pyrazoline derivatives. Asian J. Pharm. Clin. Res. 2012; 5(4): 42-46
Kumudha D, Leonard JT, Muthumani M, Chidhambaranathan N, Kalavathi T. Synthesis and evaluation of some 1,2,4-triazole derivatives as anticonvulsant, anti-inflammatory and antimicrobial agents. Asian J. Pharm. Clin. Res. 2013; 6(2): 5-8
How to Cite
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.