Abstract
Fluoroquinolones represent an interesting synthetic class of antimicrobial agents with broad spectrum and potent activity. Since the discovery of nalidixic acid, the prototype of quinolones, several structural modifications to the quinolone nucleus have been carried out for improvement of potency, spectrum of activity, and to understand their structure activity relationship (SAR). The C-7 substituent was reported to have a major impact on the activity. Accordingly, Substitution at C-7 or its N-4-piperazinyl moiety was found to affect potency, bioavailability, and physicochemical properties. Also, it can increase the affinity towards mammalian topoisomerases that may shift quinolones from antibacterial to anticancer candidates. Moreover, the presence of DNA topoisomerases in both eukaryotic and prokaryotic cells makes them excellent targets for chemotherapeutic intervention in antibacterial and anticancer therapies. Based on this concept, several fluoroquionolones derivatives have been synthesized and biologically evaluated as antibacterial, antituberculosis, antiproliferative, antiviral and antifungal agents. This review is an attempt to focus on the therapeutic prospects of fluoroquinolones with an updated account on their atypical applications such as antitubercular and anticancer activities.
Keywords: Fluoroquinolones, ciprofloxacin, antibacterial, antitubercular, antiproliferative, SAR, antibiotic trends.
[PMID: 20050522]
[http://dx.doi.org/10.1016/S0167-4781(98)00127-4] [PMID: 9748496]
[http://dx.doi.org/10.1021/jm501881c] [PMID: 25738967]
[http://dx.doi.org/10.1128/MMBR.00016-10] [PMID: 20805405]
[http://dx.doi.org/10.1038/355167a0] [PMID: 1729651]
[http://dx.doi.org/10.1016/0163-7258(93)90056-J] [PMID: 8361993]
[http://dx.doi.org/10.1021/bi00435a038] [PMID: 2546584]
[PMID: 22365088]
[http://dx.doi.org/10.14233/ajchem.2013.14738]
[http://dx.doi.org/10.1093/jac/33.4.685] [PMID: 8056688]
[http://dx.doi.org/10.1002/(SICI)1098-1128(199609)16:5<433:AID-MED3>3.0.CO;2-W] [PMID: 8865150]
[http://dx.doi.org/10.1099/00222615-44-5-320] [PMID: 8636945]
[http://dx.doi.org/10.1021/jm00149a003] [PMID: 3934382]
[http://dx.doi.org/10.7439/ijpc.v2i4.755]
[http://dx.doi.org/10.1086/430066] [PMID: 15889370]
[http://dx.doi.org/10.1164/ajrccm.163.5.2007122] [PMID: 11316634]
[http://dx.doi.org/10.1164/rccm.2309011] [PMID: 14644920]
[http://dx.doi.org/10.1016/j.ejmech.2014.08.063] [PMID: 25173851]
[http://dx.doi.org/10.1016/j.ejmech.2016.01.052] [PMID: 26871658]
[http://dx.doi.org/10.1016/j.bmcl.2013.03.118] [PMID: 23602443]
[http://dx.doi.org/10.1080/09273940600976953] [PMID: 17162605]
[http://dx.doi.org/10.1016/j.ejmech.2010.09.036] [PMID: 20933306]
[http://dx.doi.org/10.1016/j.bmcl.2007.07.073] [PMID: 17804222]
[http://dx.doi.org/10.1016/j.apsb.2011.11.003]
[http://dx.doi.org/10.1158/1078-0432.CCR-09-2236] [PMID: 20233886]
[http://dx.doi.org/10.1016/j.jmgm.2013.07.004] [PMID: 23911994]
[http://dx.doi.org/10.1016/j.bmc.2014.02.046] [PMID: 24657052]
[http://dx.doi.org/10.1111/j.1469-0691.2005.01131.x] [PMID: 15760423]
[PMID: 10954961]
[http://dx.doi.org/10.1016/j.survophthal.2004.01.005] [PMID: 15028482]
[http://dx.doi.org/10.1016/S0924-8579(98)00059-4] [PMID: 9916897]
[http://dx.doi.org/10.3345/kjp.2013.56.5.196] [PMID: 23741232]
[PMID: 20957609]
[http://dx.doi.org/10.1128/AAC.01374-09] [PMID: 20176911]
[http://dx.doi.org/10.1128/AAC.01201-10] [PMID: 21135179]
[http://dx.doi.org/10.2165/11632780-000000000-00000] [PMID: 22650326]
[http://dx.doi.org/10.1016/j.ejmech.2015.08.015] [PMID: 26363871]
[http://dx.doi.org/10.1016/j.tim.2014.04.007] [PMID: 24842194]
[http://dx.doi.org/10.2174/1381612013398013] [PMID: 11254893]
[http://dx.doi.org/10.1146/annurev.biochem.70.1.369] [PMID: 11395412]
[http://dx.doi.org/10.3201/eid0702.010239] [PMID: 11294736]
[http://dx.doi.org/10.1128/AAC.01617-06] [PMID: 17724149]
[http://dx.doi.org/10.1093/nar/gkt124] [PMID: 23460203]
[http://dx.doi.org/10.1016/j.gene.2013.04.008] [PMID: 23612251]
[http://dx.doi.org/10.1006/jmbi.2001.4838] [PMID: 11469868]
[http://dx.doi.org/10.2174/156802609789630947] [PMID: 19747119]
[http://dx.doi.org/10.1080/15257770008033048] [PMID: 11097055]
[http://dx.doi.org/10.1016/S1369-5274(99)00008-9] [PMID: 10508721]
[http://dx.doi.org/10.1016/0968-0896(96)83749-7] [PMID: 8689241]
[http://dx.doi.org/10.1021/jm000153x] [PMID: 11020298]
[http://dx.doi.org/10.1086/321846] [PMID: 11524717]
[PMID: 2850902]
[http://dx.doi.org/10.1093/jac/33.4.685] [PMID: 8056688]
[http://dx.doi.org/10.1248/cpb.44.1074] [PMID: 8689718]
[http://dx.doi.org/10.1093/jac/48.2.195] [PMID: 11481288]
[http://dx.doi.org/10.1016/j.bmc.2009.04.027] [PMID: 19419875]
[http://dx.doi.org/10.2174/0929867013373435] [PMID: 11172695]
[http://dx.doi.org/10.1093/jac/39.suppl_2.1]
[http://dx.doi.org/10.1128/AAC.42.11.2978] [PMID: 9797236]
[http://dx.doi.org/10.1128/AAC.43.12.2969] [PMID: 10582891]
[http://dx.doi.org/10.1021/jm950558v] [PMID: 8558512]
[http://dx.doi.org/10.1021/jm990191k] [PMID: 10514290]
[http://dx.doi.org/10.2174/157340609789117859] [PMID: 19534679]
[http://dx.doi.org/10.1016/j.tet.2016.03.038] [PMID: 27642196]
[http://dx.doi.org/10.1016/j.carres.2010.01.016] [PMID: 20167309]
[http://dx.doi.org/10.1517/13543784.11.2.233] [PMID: 11829714]
[http://dx.doi.org/10.1128/CMR.16.3.463-496.2003] [PMID: 12857778]
[http://dx.doi.org/10.1016/j.bmcl.2015.12.049] [PMID: 26725953]
[http://dx.doi.org/10.2174/0929867322666150818103836] [PMID: 26282941]
[http://dx.doi.org/10.3797/scipharm.1307-25] [PMID: 24634839]
[http://dx.doi.org/10.1016/j.tube.2013.02.017] [PMID: 23523640]
[http://dx.doi.org/10.1016/j.pupt.2014.04.006] [PMID: 24792579]
[http://dx.doi.org/10.1016/j.ejmech.2015.10.008] [PMID: 26544629]
[http://dx.doi.org/10.1002/med.21262] [PMID: 22622957]
[http://dx.doi.org/10.1016/j.ejmech.2006.12.034] [PMID: 17316916]
[http://dx.doi.org/10.1016/j.bmcl.2005.07.005] [PMID: 16115766]
[http://dx.doi.org/10.1021/cr030101q] [PMID: 15700957]
[http://dx.doi.org/10.1016/j.ejmech.2008.09.012] [PMID: 18950903]
[http://dx.doi.org/10.1016/j.biopha.2008.01.016] [PMID: 18328669]
[http://dx.doi.org/10.1016/j.ejmech.2010.04.027] [PMID: 20493593]
[http://dx.doi.org/10.1248/cpb.55.894] [PMID: 17541188]
[http://dx.doi.org/10.1016/j.ejmech.2008.01.042] [PMID: 18358571]
[http://dx.doi.org/10.1146/annurev.bi.64.070195.000333] [PMID: 7574484]
[http://dx.doi.org/10.1016/j.bmcl.2006.08.045] [PMID: 16945530]
[http://dx.doi.org/10.1016/j.bmc.2005.04.005] [PMID: 15911308]
[http://dx.doi.org/10.1016/j.ejmech.2013.10.055] [PMID: 24333580]
[http://dx.doi.org/10.1016/j.bmcl.2014.03.010] [PMID: 24684842]
[http://dx.doi.org/10.1016/j.bmcl.2016.03.050] [PMID: 27020299]
[http://dx.doi.org/10.1016/j.ejmech.2015.09.030] [PMID: 26435513]
[http://dx.doi.org/10.1016/j.ejmech.2009.05.001] [PMID: 19482387]
[http://dx.doi.org/10.1016/j.bmcl.2012.07.040] [PMID: 22884110]
[http://dx.doi.org/10.1016/j.biopha.2007.10.004] [PMID: 18031974]
[http://dx.doi.org/10.1038/nrm831] [PMID: 12042765]
[http://dx.doi.org/10.1016/j.ejmech.2013.08.040] [PMID: 24090914]
[http://dx.doi.org/10.1021/jm040025z] [PMID: 15509164]
[http://dx.doi.org/10.1016/S0167-4781(98)00132-8] [PMID: 9748545]
[PMID: 10363026]
[http://dx.doi.org/10.1002/hep.20174] [PMID: 15122760]
[http://dx.doi.org/10.1002/iub.5] [PMID: 18380002]
[http://dx.doi.org/10.1038/nrc2607] [PMID: 19377506]
[http://dx.doi.org/10.1016/j.chembiol.2010.04.012] [PMID: 20534341]
[http://dx.doi.org/10.1016/0022-2836(92)90863-F] [PMID: 1335085]
[PMID: 7875053]
[http://dx.doi.org/10.1016/j.bmc.2009.06.053] [PMID: 19595598]
[http://dx.doi.org/10.2174/1568011033482279] [PMID: 14529452]
[http://dx.doi.org/10.1016/S1369-5274(99)00008-9] [PMID: 10508721]
[http://dx.doi.org/10.2174/138955706776361493] [PMID: 16613574]
[http://dx.doi.org/10.1074/jbc.274.50.35927] [PMID: 10585479]
[http://dx.doi.org/10.1016/j.bcp.2007.11.014] [PMID: 18191106]
[http://dx.doi.org/10.1186/s12885-015-1560-y] [PMID: 26260159]
[PMID: 20436225]
[http://dx.doi.org/10.4161/cbt.7.1.5136] [PMID: 18059176]
[http://dx.doi.org/10.1038/sj.bjc.6600079] [PMID: 11875713]
[http://dx.doi.org/10.1002/art.23518] [PMID: 18512786]
[http://dx.doi.org/10.1038/sj.bjc.6603355] [PMID: 17047652]
[http://dx.doi.org/10.1371/journal.pone.0047796] [PMID: 23133524]
[http://dx.doi.org/10.1016/j.mrgentox.2011.11.012] [PMID: 22142834]
[http://dx.doi.org/10.1016/j.cbi.2013.01.003] [PMID: 23340199]
[http://dx.doi.org/10.1186/s12941-016-0150-4] [PMID: 27215369]
[http://dx.doi.org/10.1016/0960-894X(95)00160-U]
[http://dx.doi.org/10.1016/j.ejmech.2007.01.029] [PMID: 17408810]
[http://dx.doi.org/10.1128/AAC.36.1.81] [PMID: 1317151]
[PMID: 10197041]
[http://dx.doi.org/10.1128/AAC.38.1.130] [PMID: 8141566]
[http://dx.doi.org/10.1128/AAC.44.2.320-325.2000] [PMID: 10639357]
[http://dx.doi.org/10.1073/pnas.91.23.11007] [PMID: 7971998]
[http://dx.doi.org/10.1128/AAC.36.4.751] [PMID: 1323952]
[http://dx.doi.org/10.1016/j.biopha.2005.06.006] [PMID: 16263236]
[http://dx.doi.org/10.1016/j.ejmech.2004.11.008] [PMID: 15804535]
[http://dx.doi.org/10.1016/j.bmc.2016.07.070] [PMID: 27555286]
[http://dx.doi.org/10.1016/j.cclet.2012.01.029]
[http://dx.doi.org/10.1016/j.bmcl.2013.09.077] [PMID: 24138941]
[http://dx.doi.org/10.1016/j.bmcl.2011.01.061] [PMID: 21316236]
[http://dx.doi.org/10.1371/journal.pone.0010186] [PMID: 20419121]
[http://dx.doi.org/10.1097/JTO.0b013e318200e509] [PMID: 21252718]
[http://dx.doi.org/10.1093/jac/dkn473] [PMID: 19109335]
[PMID: 9614214]
[http://dx.doi.org/10.1128/AAC.41.6.1250] [PMID: 9174179]
[http://dx.doi.org/10.1016/S0960-894X(99)00537-5] [PMID: 10560726]
[http://dx.doi.org/10.1016/S0960-894X(02)00003-3] [PMID: 11858992]
[http://dx.doi.org/10.1093/jac/dki328] [PMID: 16150861]
[http://dx.doi.org/10.1128/AAC.00988-08] [PMID: 19015358]
[http://dx.doi.org/10.1086/650698] [PMID: 20146631]
[http://dx.doi.org/10.1021/jm070609b] [PMID: 18281931]
[http://dx.doi.org/10.1177/095632029800900504] [PMID: 9875393]
[PMID: 2405016]
[http://dx.doi.org/10.1086/428051] [PMID: 15942877]
[http://dx.doi.org/10.1021/bi5000564] [PMID: 24576155]
[http://dx.doi.org/10.1128/AAC.45.1.105-116.2001] [PMID: 11120952]
[PMID: 11321578]
[http://dx.doi.org/10.1093/jac/dkg223] [PMID: 12697643]