Document Type: Original Article

Authors

1 Guru Gobind Singh College of Pharmacy, Yamuna Nagar-135001, Haryana, India

2 Ex Scientist G, Department of Natural Product Chemistry, Indian Institute of Integrative Sciences (IIIM), Jammu

Abstract

The efficient synthesis of novel 2,2-dimethyl-chroman-6-yl pentadienoic acid amides (7a-e) as synthetic piperine analogs has been established by the condensation of 5-(2,2-dimethyl-chroman-6-yl)-4-methyl-penta-2,4-dienoic acid 6 with various aromatic amines. All the synthesized piperine analogs were bioevaluated for their potential as inhibitors of multidrug efflux pump NorA overexpressing Staphylococcus aureus SA 1199B. Out of all the prepared analogs, 5-(2,2-dimethyl-chroman-6-yl)-4-methyl-penta-2,4-dienoic acid ethyl ester 5 and 5-(2,2-Dimethyl-chroman-6-yl)-4-methyl-2E,4E-pentadienoic acid pyrrolidide 7d were found promising. The active compounds were also evaluated for their synergistic effect with ciprofloxacin, whose results substantially increase the activity of ciprofloxacin against both Nora overexpressing and wild type Staphylococcus aureus isolates. Structures of the synthesized compounds have been elucidated on the basis of spectral data (IR, 1H NMR and Mass analysis).

Graphical Abstract

Keywords

Main Subjects

[1] Karchmer A.W. Clin. Infect Dis., 2000, 31:S139

[2] Weisblum B. Antimicrob. Agents Chem., 1995, 39:577

[3] Ruiz J. J. Antimicrob. Chem., 2003, 51:1109

[4] Bush K., Miller G.H. Curr. Opin. Microbiol., 1998, 1:509

[5] Courvalin P. Antimicrob. Agents Chem., 1994, 38:1447

[6] Rogers B.L. Curr. Opin. Drug. Discov. Devel., 2004, 7:211

[7] Ackermann G., Rodloff A.C. J. Antimicrob. Chem., 2003, 51:497

[8] Bozdogan B., Appelbaum P.C. Int. J. Antimicrob. Agents, 2004, 23:113

[9] Hooper D.C. Clin. Infect Dis., 2005, 40:1811

[10] Webber M.A., Piddock L.J.V. J. Antimicrob. Chem., 2003, 51:9

[11] Van Bambeke F., Balzi E., Tulkens P.M. Biochem. Pharmacol., 2000, 60:457

[12] Hsieh P.C., Siegel S.A., Rogers B., Davis D., Lewis K. Proc. Nat. Acad. Sci., 1998, 95:6602

[13] Lomovskaya O., Lee A., Hoshino K., Hoshino K., Mistry A., Warren M.S., Boyer E., Chamberland S., Lee V.J.  Antimicrob. Agents Chem., 1999, 43:1340

[14] Khan I.A., Mirza Z.M., Kumar A., Verma V. Qazi G.N. Antimicrob. Agents Chem., 2006, 50:810

[15] Koul S., Koul J.L., Taneja S.C., Gupta P., Khan I.A., Mirza Z.M., Kumar A., Johri R.K., Pandita M., Khosa A., Tikko A.K., Sharma S.C., Verma V., Qazi G.N. U. S. Patent 103527, 2006.

[16] Kumar A.,  Khan  I.A., Koul S., Koul  J.L., Taneja  S.C., Ali I., Ali F., Sharma S., Mirza Z.M., Kumar M.,  Sangwan P.L., Gupta P., Thota N., Qazi G.N. J. Antimicrob. Chem., 2008, 61:1270