Recent Strategies in Design of Antitumor and Antibacterial Fluoroquinolones

Abstract

Fluoroquinolones are known widely used synthetic antibacterial agents. Generally, there were some obstacles associated with their therapeutic use. Moreover, many research studies all over the world proved the variable biological effects of fluoroquinolones such as antituberculosis, anticancer, or even antiviral activities. The current review is focused on modifications that occurred in the fluoroquinolone scaffold for their repositioning from antibacterial into anticancer agents especially modifications at C-7 or at the carboxylic C-3 groups. In addition, it includes the recent research studies carried out to improve the potency, spectrum of activity, or pharmacokinetics of antibacterial fluoroquinolones. Hence, this review may be useful for researchers in the design and synthesis of new fluoroquinolones with improved biological activities.

Recent advances in the synthesis of pharmaceutically active 4-quinolone and its analogues: a review

“…Moreover, they revealed a potent pro-apoptotic effect through the induction of apoptosis and an increase in the level of active caspase-3 compared to control and cell cycle arrest at the G2/M phase. 6 Generally, SAR studies revealed that Azoles connecting to the C-8 and N-1 positions, small ring at the C-2 position, amide, ester, and heterocycles, such as azoles at the C-3 position, -H, -F, -Me, and -OMe substitutes at the C-5 position, and N, C-H, C-F substituted at the C-8 position, can improve anticancer activity (Fig. 6).…”

“…61 Voreloxin 155 was the first quinolone derivative approved by the FDA as a therapy for acute myeloid leukemia. 6 In 2017, Zhang and coworkers reported the synthesis of a series of novel water-soluble 4-quinolone-3-carboxamide derivatives 156 for anticancer activity against seven human tumor cell lines. The authors revealed that compound 156 showed reasonable anticancer activities against tested tumor cell lines (laryngeal carcinoma (Hep-2), breast carcinoma (MCF-7), gastric carcinoma (BGC-823), liver carcinoma (HepG2), cervical carcinoma (HeLa), prostate carcinoma (PC-3) and colorectal carcinoma (HCT-8, HCT-116 and RKO)) with IC 50 values lower than 10.0 μM.…”

“…4-Quinolone is one of the most widely used N-hetero-aromatic compounds, which possess a bicyclic system of pyridine moiety fused with aromatic or hetero-aromatic scaffold at two adjacent carbons and have a carbonyl group at C-4. 6,7 Quinolones are present in equilibrium through tautomerism, the minor tautomeric form of 4-quinolone (1) and its other version 4-hydroxyquinolone (1a), as depicted in Fig. 2.…”

“…4-Quinolone is one of the most widely used N -hetero-aromatic compounds, which possess a bicyclic system of pyridine moiety fused with aromatic or hetero-aromatic scaffold at two adjacent carbons and have a carbonyl group at C-4. 6,7…”