Fluoroquinolone antibiotics: An overview

Abstract

Fluoroquinolones are the type of antibacterial agents more extensively used from the past few years and will be continued to be used even in the next decade. The fluoroquinolones show their action by inhibiting the DNA gyrase and topoisomerase enzymes. The main mechanism fluoroquinolones is mutations that alter the accumulation of fluoroquinolones in bacteria. The broad use of the fluoroquinolones is discussed. They are useful in the treatment of urinary tract infections, prostatitis, sexually transmitted diseases, gastrointestinal infections, osteomyelitis, and respiratory tract infections. Their structure–activity relationship is also discussed and that is helpful in ongoing new researches on quinolones that may enhance the antibacterial activity of quinolones.

A multivariate comparative clinical pharmacotherapeutic efficacy and chronopharmacovigilance assessment study of ofloxacin, one of the commonplace, TGFβ1 inducing and telomerase impairing fluoroquinolones, in treating acute gastroenteritis, chronic obstructive pulmonary disease, new drug-sensitive tuberculosis, recurrent mixed cutaneous infections, and post-surgical refractory wound infections, among the global patients, with heterogenous pharmacogeographic and pharmacogenomic constitution

“…DNA gyrase establishes negative super-helical twists in the bacterial DNA. 4 Ofloxacin has an inhibitory effect on DNA gyrase, DNA topoisomerase IV and IL-1α, IL-6, IL-8, TNF; and a superinducing effect on IL-2.…”

“…This study re-emphasised, with all its investigative aspects, that ofloxacin was, is, and would always remain an extremely necessary 'essential drug', as it has numerous therapeutic uses, high efficacy, confirmed safety, easy availability and accessibility, and suitability in both acute and chronic complicated disease conditions; shown also in several studies, performed throughout the world. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] The initial quinolone compounds had a limited spectrum of activity against gram negative organisms thus, restricting their clinical use. To the core quinolone ring structure, addition of moieties like fluorine at C6 and piperazinyl at C7, increased the gram-negative coverage and improved the systemic retention of the drugs.…”

“…The quinolone structure consists of a bicyclic system with a substituent at position N-1, a carboxyl group at position 3, a keto group at position 4, a fluorine atom at position 6, and a substituent (often nitrogen heterocycle moiety) at the C-7. 4 Ofloxacin is quite significantly efficacious for its (a) bactericidal inhibitory effect on: (i) DNA gyrase, caused by the binding of fluoroquinolones to the A subunits (gyr A), thus inhibiting the replication and transcription of bacterial DNA, responsible for the proper functioning of the cell, and the subsequent change of conformity of DNA gyrase molecule caused by the binding of fluoroquinolones to the DNA binding groove between A (gyr A) and B (gyr B) subunits; (ii) Par C subunits (par C) and Par E subunits (par E) of DNA topoisomerase IV, thus inhibiting decatenation and relaxation of DNA and segregation of replicating chromosomes or plasmids in bacteria; (iii) Pro-inflammatory cytokines, like interleukins: IL-1α, IL-6, IL-8, and tumour necrosis factor , and, (b) a superinducing effect on IL-2, causing an indirect immunomodulation, tending to increase both the growth and activity of T and B lymphocytes; and also affecting the development of immune responses by influencing of the expression of other cytokines and mediators. [1][2][3][4][5] The dual inhibitory activity of fluoroquinolones against the bacterial replication enzymes, DNA gyrase and topoisomerase IV, protects them from the development of resistance.…”

“…4 Ofloxacin is quite significantly efficacious for its (a) bactericidal inhibitory effect on: (i) DNA gyrase, caused by the binding of fluoroquinolones to the A subunits (gyr A), thus inhibiting the replication and transcription of bacterial DNA, responsible for the proper functioning of the cell, and the subsequent change of conformity of DNA gyrase molecule caused by the binding of fluoroquinolones to the DNA binding groove between A (gyr A) and B (gyr B) subunits; (ii) Par C subunits (par C) and Par E subunits (par E) of DNA topoisomerase IV, thus inhibiting decatenation and relaxation of DNA and segregation of replicating chromosomes or plasmids in bacteria; (iii) Pro-inflammatory cytokines, like interleukins: IL-1α, IL-6, IL-8, and tumour necrosis factor , and, (b) a superinducing effect on IL-2, causing an indirect immunomodulation, tending to increase both the growth and activity of T and B lymphocytes; and also affecting the development of immune responses by influencing of the expression of other cytokines and mediators. [1][2][3][4][5] The dual inhibitory activity of fluoroquinolones against the bacterial replication enzymes, DNA gyrase and topoisomerase IV, protects them from the development of resistance. [1][2][3][4][5][6][7] Quinolones, like ofloxacin, possess an ever-expanding spectrum of clinical indications like : (i) multiple, multiresistant, concurrent and recurrent infections, including drug-resistant tuberculosis, drug-resistant leprosy and coronaviridae-19; (ii) refractory inflammations; (iii) diabetes mellitus; (iv) obesity; (v) anti-cancer radiotherapy; (vi) immune disorders; (vii) malignancies; and (vii) complicated and refractory diseases and disorders; due to their profound a. bactericidal, b. antiviral, c. anti-fungal, d. anti-protozoal, e. comedolytic, f. anti-comedogenic, g. anti-inflammatory, h. anti-diabesity, i. radioprotective, j. immunomodulatory (transcription factors -like NF-kB/NFAT/AP1 -mediated, and on regulation of cyclic AMP or phosphodiesterase), k. antineoplastic, pro-apoptotic, p53 mediated S phase arrest/TGF1 targeted G2 phase cell cycle arrest, antiproliferative (by suppression of OncomiR expression, impairment of telomerase activity, DNA synthesis inhibition, inhibition of cell colony formation, mitochondrial membrane potential disruption), antimetastatic (migration, invasion and metastasis-MET inhibitor), and cancer stemness regulator potential.…”

“…[1][2][3][4][5][6][7] Quinolones, like ofloxacin, possess an ever-expanding spectrum of clinical indications like : (i) multiple, multiresistant, concurrent and recurrent infections, including drug-resistant tuberculosis, drug-resistant leprosy and coronaviridae-19; (ii) refractory inflammations; (iii) diabetes mellitus; (iv) obesity; (v) anti-cancer radiotherapy; (vi) immune disorders; (vii) malignancies; and (vii) complicated and refractory diseases and disorders; due to their profound a. bactericidal, b. antiviral, c. anti-fungal, d. anti-protozoal, e. comedolytic, f. anti-comedogenic, g. anti-inflammatory, h. anti-diabesity, i. radioprotective, j. immunomodulatory (transcription factors -like NF-kB/NFAT/AP1 -mediated, and on regulation of cyclic AMP or phosphodiesterase), k. antineoplastic, pro-apoptotic, p53 mediated S phase arrest/TGF1 targeted G2 phase cell cycle arrest, antiproliferative (by suppression of OncomiR expression, impairment of telomerase activity, DNA synthesis inhibition, inhibition of cell colony formation, mitochondrial membrane potential disruption), antimetastatic (migration, invasion and metastasis-MET inhibitor), and cancer stemness regulator potential. [1][2][3][4][5][6][7][8][9][10][11][12] As an anti-cancer drug, ofloxacin, when administered, has the following actions: (i) in a dose >200 μg/ml for >48 hours, in transitional cell carcinoma, ofloxacin inhibits proliferation by impairment of telomerase activity in MBT-2 and T24 type of tumour cells; (ii) at a dose of 0-800 μg/ml for 24-120 hours, in transitional cell carcinoma, ofloxacin inhibits proliferation and DNA synthesis in TCCSUP, T24 and J82 type of tumour cells; (iii) 1000 μg/ml ofloxacin, administered for 24-96 hours, in bladder cancer, would inhibit proliferation in the T24, HTB9 and TccSup type tumour cells; (iv) at a dosage of 100 μg/ml for 24 hours, under the exposure of 3.5 W/cm 2 UVA for 30 mins, ofloxacin causes apoptosis and S/G2 -phase arrest in the HeLa and A431 tumour cell lines, in epidermoid carcinoma, by DNA plasmid photocleavage via carbocation; (v) with 0-100 μg/ml, administered for 0-5 days, ofloxacin inhibits proliferation by suppressing OncomiR expression, in the A375, Mel-Ho, and Mel-Juso type melanoma tumour cells, MCF7 type breast tumour cells, A2780 type ovarian tumour cells and H1299 type lung tumour cells, by suppressing OncomiRs targeting splicing machinery, and activating the wild type p53, with the downregulation of MdmX. 1,2,[8]…”