Abstract
A series of novel N-Sulphonamidomethyl piperzinyl fluoroquinolones were synthesized and screened antiviral activity. Eight compounds were synthesized through modifying the N4-hydrogen of piperazine in fluoroquinolones with formaldehyde and sulphanomides by Mannich reactions. The structures of the synthesized compounds were characterized by means of their IR and 1H-NMR spectral data. Synthesized compounds were screened for antiviral activity against influenza A (H1N1, H3N2, H5N1) and influenza B viruses in MDCK cell culture. The antiHIV activities of the new compounds were screened for antiviral activity against replication of HIV-1(IIIB) in MT-4 cells. Cytotoxicity of the synthesized compounds was also tested in mock-infected MDCK and MT-4 cells. Compound CF-SD and CF-SDM inhibits the influenza A (H1N1) and compound GF-SDM inhibit the replication of influenza A (H5N1) and B in MDCK cells. All compounds displayed cytostatic propertity in MT-4 cells. Among the compounds tested, GF-SDM (CC50=39.44 μM) most toxic compound in this series.
Highlights
1 containing unsubstituted phenyl ring in 2nd position of the 4-phenyl morpholine exhibits greater activity than the substituted one
We report a study of replacing the N4-hydrogen of piperazine in flouroquinolone with different substitutions of sulphonamide moiety via mannich reactions to form N-sulphonamido- methyl flouroquinolone derivatives
Compound CF-SD and CF-SDM inhibited the replication of influenza A (H1N1)
Summary
Scheme 1: Synthesis of N-sulphonamidomethyl fluoroquinolones For NF-SA, R1 is ethyl, R2 is H and R3 is benzenesulphonamide; for NF-SD, R1 is ethyl, R2 is H and R3 is -(2-pyrimidinyl)benzenesulphonamide; NF-SDM, R1 is ethyl, R2 is H and R3 is -(4,6-dimethyl-2-primidiniyl)-benzenesulphonamide; for GF-SA, R1 is cyclopropyl, R2 is methoxy and R3 is benzenesulphonamide; for GF-SD, R1 is cyclopropyl, R2 is methoxy and R3 is -(2-pyrimidinyl)benzenesulphonamide; for GF-SDM, R1 is cyclopropyl, R2 is methoxy and R3 is -(4,6-dimethyl-2-primidiniyl)-benzenesulphonamide; for CF-SD, R1 cyclopropyl, R2 is H and R3 is -(2-pyrimidinyl)benzenesulphonamide; for CF-SDM, R1 is cyclopropyl, R2 is H and R3 is -(4,6-dimethyl -2-primidiniyl)-benzenesulphonamide. 1H-NMR (DMSO-d6) δ ppm: 0.42 (s, 2H, cyclopropyl), 1.36 (s, 1H, cyclopropyl), 2.2 (s, 6H, 2×CH3), 2.6 (s, 4H,-piperazinyl), 3.5 (s, 4H,piperazinyl), 3.23 (s, 3H, -OCH3), 4.0 (s, 1H, NH), 4.12 (s, 2H, -N-CH2-N-), 6-7.7 (m,7H, Ar-H), 11.0 (s, 1H, COOH); EI-MS (m/z): 651. Compound CF-SD and CF-SDM inhibited the replication of influenza A (H1N1) Their inhibitory concentration (EC50) was 16 and 18 μg/ml, respectively, whereas the cytotoxic concentration (CC50) was found to be more than 100 μg/ml (Table 1). Cytotoxic concentrations of test compounds were found to be 39-75 μM, whereas the standard AZT showed 65.9 μM in mock infected MT-4 cells Compound GF-SDM (CC50=39.44 μM)displayed marked cytostatic activity in the MT-4 cells. These lead molecules are suitable for designing newer derivatives against influenza viruses based upon promising antiviral activity seen
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