ANTIMICROBIAL AND CHITINASE INHIBITORY ACTIVITIES OF 7-BENZAMIDOCOUMARINS
DOI:
https://doi.org/10.22159/ajpcr.2019.v12i7.33155Keywords:
Amidocoumarins,, Coumarin,, Antimicrobial,, Antibacterial,, Antifungal,, ChitinaseAbstract
Objective: The aim of this study was to examine in vitro antimicrobial activity of a series of 7-benzamidocoumarin derivatives against three Gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus, and Bacillus pumilus), three Gram-negative bacteria (Escherichia coli, Klebsiella pneumonia, and Salmonella typhi), and three fungi (Candida albicans, Candida tropicalis, and Aspergillus niger) by 2-fold serial dilution method.
Materials and Methods: The compounds were synthesized by amide coupling of 7-amino-4-methyl coumarin 5 and 7-amino-4-chloromethyl coumarin 6 with different aromatic acids 7 (a-h) and heteroaromatic acids 8 (i-j) in the presence of phosphorous trichloride as an acid catalyst in acetonitrile. The synthesized compounds were evaluated for antimicrobial and chitinase inhibitory activity.
Results: Compounds 9, 11, 12, 21, and 23 showed good antibacterial activity with minimum inhibitory concentration (MIC) ranging from 6.25 to 50 μg/mL. Among them, compound 21 was the most active molecule with MIC 6.25 μg/mL against S. aureus and 6.25 μg/mL against, B. pumilus and S. typhi. Compounds 11 and 21 were the most potent antifungal candidates with MIC 6.25–25 μg/mL against C. albicans and C. tropicalis. All the compounds were also evaluated for their chitinase inhibitory property and among them; compound 9 emerged as strong inhibitor of the enzyme.
Conclusion: Some of the compounds showed very good antimicrobial activities. Among these, compound 21 showing potent antimicrobial activities against five of the nine microbial strains examined in this study, was the most active compound of the series. Some of the compounds also showed chitinase inhibitory properties. This study also provides a starting point for investigating the structure-activity relationships (SARs) of synthetic 7-benzamidocoumarins.
Downloads
References
Peng XM, Cai GX, Zhou CH. Recent developments in azole compounds as antibacterial and antifungal agents. Curr Top Med Chem 2013;13:1963-2010.
Rai J, Randhawa GK, Kaur M. Recent advances in antibacterial drugs. Int J Appl Basic Med Res 2013;3:3-10.
Simmons KJ, Chopra I, Fishwick CW. Structure-based discovery of antibacterial drugs. Nat Rev Microbiol 2010;8:501-10.
Jayanthi CR, Chaithra KN, Reddy NS. A profile of adverse drug reactions to antimicrobial agents at a tertiary care hospital. Indian J Pharm Pharmacol 2017;4:16-21.
Saeed AM. Pharmaco bacteriological investigation of erythromycin, cephalexin, cephradine, amoxycillin and ciprofloxacin against different strains of Klebsiella pneumonaie, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Salmonella species. Indian J Pharm Pharmacol 2018;5:153-8.
Walsh C. Molecular mechanisms that confer antibacterial drug resistance. Nature 2000;406:775-81.
Denning DW, Bromley MJ. Infectious disease. How to bolster the antifungal pipeline. Science 2015;347:1414-6.
Badiee P, Hashemizadeh Z. Opportunistic invasive fungal infections: Diagnosis & clinical management. Indian J Med Res 2014;139:195-204.
Brown GD, Denning DW, Gow NA, Levitz SM, Netea MG, White TC. Hidden killers: Human fungal infections. Sci Transl Med 2012;4:165rv13.
Riveiro ME, De Kimpe N, Moglioni A, Vázquez R, Monczor F, Shayo C, et al. Coumarins: Old compounds with novel promising therapeutic perspectives. Curr Med Chem 2010;17:1325-38.
Borges F, Roleira F, Milhazes N, Santana L, Uriarte E. Simple coumarins and analogues in medicinal chemistry: Occurrence, synthesis and biological activity. Curr Med Chem 2005;12:887-916.
Hoult JR, Payá M. Pharmacological and biochemical actions of simple coumarins: Natural products with therapeutic potential. Gen Pharmacol 1996;27:713-22.
Barot KP, Jain SV, Kremer L, Singh S, Ghate MD. Recent advances and therapeutic journey of coumarins: Current status and perspectives. Med Chem Res 2015;24:2771-98.
Gaudino EC, Tagliapietra S, Martina K, Palmisano G, Cravotto G. Recent advances and perspectives in the synthesis of bioactive coumarins. RSC Adv 2016;6:46394-405.
Singh LK, Priyanka, Singh V, Katiyar D. Design, synthesis and biological evaluation of some new coumarin derivatives as potential antimicrobial agents. Med Chem 2015;11:128-34.
Misra S, Singh LK, Priyanka, Gupta J, Misra-Bhattacharya S, Katiyar D. Synthesis and biological evaluation of 4-oxycoumarin derivatives as a new class of antifilarial agents. Eur J Med Chem 2015;94:211-7.
Whittemore M, Guillon NH, McNeel T, Rapp R, Mariano T, Heck D, Laskin J. Synthetic approaches to 4,8-dimethyl-4’-(N-pyridinium-methyl)-4’,5’-dihydropsoralens and their activity against PAM 212 keratinocytes. Heterocycles 2001;55:1081-94.
Kathuria A, Priya N, Chand K, Singh P, Gupta A, Jalal S, et al. Substrate specificity of acetoxy derivatives of coumarins and quinolones towards calreticulin mediated transacetylation: Investigations on antiplatelet function. Bioorg Med Chem 2012;20:1624-38.
Stefanachi A, Favia AD, Nicolotti O, Leonetti F, Pisani L, Catto M, et al. Design, synthesis, and biological evaluation of imidazolyl derivatives of 4,7-disubstituted coumarins as aromatase inhibitors selective over 17-α-hydroxylase/C17-20 lyase. J Med Chem 2011;54:1613-25.
Priyanka, Neelabh, Tiwari N, Sharma RK, Gupta P, Misra-Bhattacharya S, et al. Synthesis, structure elucidation, homology modeling and antifilarialactivity of 7-benzamidocoumarin derivatives. Chem Select 2019;4:3300-7.
Vipra A, Desai SN, Junjappa RP, Roy P, Poonacha N, Ravinder P, et al. Determining the minimum inhibitory concentration of bacteriophages: Potential advantages. Adv Microbiol 2013;3:181-90.
Gangwar M, Singh V, Pandey AK, Tripathi CK, Mishra BN. Purification and characterization of chitinase from Streptomyces violascens NRRL B2700. Indian J Exp Biol 2016;54:64-71.
National Committee for Clinical Laboratory Standards. Approved Standard Document. M27-A2, Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts. Wayne, PA: National Committee for Clinical Laboratory Standards; 2002.
Hartl L, Zach S, Seidl-Seiboth V. Fungal chitinases: Diversity, mechanistic properties and biotechnological potential. Appl Microbiol Biotechnol 2012;93:533-43.
Dickinson K, Keer V, Hitchcock CA, Adams DJ. Chitinase activity from Candida albicans and its inhibition by allosamidin. J Gen Microbiol 1989;135:1417-21.
Houston DR, Synstad B, Eijsink VG, Stark MJ, Eggleston IM, van Aalten DM. Structure-based exploration of cyclic dipeptide chitinase inhibitors. J Med Chem 2004;47:5713-20.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.
