Synthesis and antimicrobial activity of some 2- Piperidinomethylamino-4-(7-H/substituted coumarin-3-yl)- 6-chlorosubstitutedphenyl pyrimidines

Purpose: To prepare and evaluate some 2-piperidinomethylamino-4-(7-H/substitutedcoumarin-3-yl)-6- chlorosubstitutedphenyl pyrimidines as antimicrobial agents. Methods: Some 2-piperidinomethylamino-4-(7-H/substitutedcoumarin-3-yl)-6-chlorosubstitutedphenyl pyrimidines were prepared by reacting 2-amino-4-(7-H/substitutedcoumarin-3-yl)-6- (chlorosubstitutedphenyl) pyrimidines with piperidine and formaldehyde. The chemical structures of the synthesized compounds were elucidated by Fourier transform infrared (FTIR), 1H-nuclear magnetic resonance (1H-NMR), mass spectrometry and elemental analysis. These compounds were investigated for their antimicrobial activity against ten bacteria and five fungi by serial plate dilution method using standard drugs, namely, ofloxacin and ketoconazole, respectively, and their minimum inhibitory concentrations (MICs) were also determined. Results: A total of eighteen new compounds (1a-18a) were synthesized. Compound 6a (MIC = 50 μg/mL; p < 0.05 or less) displayed the highest activity against S. aureus , E. faecalis , Staphylococcus epidermidis , B. subtilis , and B. cereus . Compound 6a further showed good activity (MIC = 25 μg/mL; p < 0.05 or less) against E. coli ; P. aeruginosa K. pneumonia , B. bronchiseptica , and P. vulgaris . Compounds 6a (MIC = 25 μg/mL; p < 0.0001) and 17a (MIC = 25 μg/mL; p < 0.0001) displayed very good activity against C. albicans , A. niger , A. flavus , M. purpureous , and P. citrinum , respectively. Analysis of structure-activity relationship revealed that the presence of bromo group at 7-postion of the coumarin moiety along with the 4-chlorophenyl group at position-6 of the pyrimidine ring is critical for antimicrobial activity against Gram-positive bacteria, Gram negative bacteria and fungi. Conclusion: The synthesized 2-piperidino derivatives are better antifungal and antibacterial agents than the earlier reported 2-morpholino derivatives, but require further investigations against other microbial strains to ascertain their broad spectrum antimicrobial activity.

Synthesis and antibacterial study of some s-substituted aliphatic analogues of 2-mercapto-5-(1-(4-toluenesulfonyl) piperidin-4-yl)-1,3,4-oxadiazole

Purpose: To synthesize a series of analogues of 1,3,4-oxadiazole and to evaluate their antibacterial activity. Methods: Ethyl piperidin-4-carboxylate (1) was mixed with 4-toluenesulfonyl chloride (2) in benignant conditions to yield ethyl 1-(4-toluenesulfonyl)piperidin-4-carboxylate (3) and then 1-(4- toluenesulfonyl)piperidin-4-carbohydrazide (4). Intermolecular cyclization of 4 into 2-mercapto-5-(1-(4- toluenesulfonyl) piperidin-4-yl)-1,3,4-oxadiazole (5) was obtained on reflux with CS2 in the presence of KOH. Molecule 5 was stirred with alkyl halides, 6a-i, in DMF in the presence of LiH to synthesize the final compounds, 7a-i. The structures of these molecules were elucidated by Fourier transform infra-red (FTIR) spectroscopy, proton nuclear magnetic resonance (1H-NMR) and electron impact mass spectrometry (EI-MS). Antibacterial activity was evaluated against five bacterial strains, namely, Salmonella typhi, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis, with ciprofloxacin used as standard antibacterial agent. Results: Out of nine synthesized derivatives, compound 7a was the most active against three bacterial strains, S. typhi, E. coli and P. aeruginosa, with minimum inhibitory concentration (MIC) of 9.11 ± 0.40, 9.89 ± 0.45 and 9.14 ± 0.72 μM, respectively, compared with 7.45 ± 0.58, 7.16 ± 0.58 and 7.14 ± 0.18 μM, respectively, for the reference standard (ciprofloxacin). Similarly, compounds 7a - 7c showed relatively good antibacterial activity against B. subtilis strain while compound 7e - 7g revealed good results against S. typhi bacterial strain. Conclusion: The results indicate that S-substituted derivatives of the parent compound are more effective antibacterial agents than the parent compound, even with minor differences in substituents