105404-65-7Relevant articles and documents
From 6-aminoquinolone antibacterials to 6-amino-7- thiopyranopyridinylquinolone ethyl esters as inhibitors of staphylococcus aureus multidrug efflux pumps
Pieroni, Marco,Dimovska, Mirjana,Brincat, Jean Pierre,Sabatini, Stefano,Carosati, Emanuele,Massari, Serena,Kaatz, Glenn W.,Fravolini, Arnaldo
, p. 4466 - 4480 (2010)
The thiopyranopyridine moiety was synthesized as a new heterocyclic base to be inserted at the C-7 position of selected quinolone nuclei followed by a determination of antibacterial activity against strains of Staphylococcus aureus. Selected thiopyranopyridinylquinolones showed significant antimicrobial activity, including strains having mutations in gyrA and grlA as well as other strains overexpressing the NorA multidrug (MDR) efflux pump. Most derivatives did not appear to be NorA substrates. The effect of the thiopyranopyridinyl substituent on making these quinolones poor substrates for NorA was investigated further. Several quinolone ester intermediates, devoid of any intrinsic antibacterial activity, were tested for their abilities to inhibit the activities of NorA (MFS family) and MepA (MATE family) S. aureus MDR efflux pumps. Selected quinolone esters were capable of inhibiting both MDR pumps more efficiently than the reference compound reserpine. Moreover, they also were able to restore, and even enhance, the activity of ciprofloxacin toward some genetically modified resistant S. aureus strains.
Light-triggered release of ciprofloxacin from an in situ forming click hydrogel for antibacterial wound dressings
Shi, Yue,Truong, Vinh X.,Kulkarni, Ketav,Qu, Yue,Simon, George P.,Boyd, Richard L.,Perlmutter, Patrick,Lithgow, Trevor,Forsythe, John S.
, p. 8771 - 8774 (2015)
Light triggered release of an antibiotic from a click crosslinked hydrogel was developed by conjugating ciprofloxacin through a photo-cleavable linker to the hydrogel network structure. Upon irradiation of the hydrogel material with UV light (365 nm) at low intensity, native ciprofloxacin was released into the surrounding environment and could be detected by HPLC. The antimicrobial activity of the released compound on Staphylococcus aureus was demonstrated.
Design of ciprofloxacin derivatives that inhibit growth of methicillin resistant staphylococcus aureus (MRSA) and methicillin susceptible staphylococcus aureus (MSSA)
Bartzatt, Ronald,Cirillo, Suat L.G.,Cirillo, Jeffrey D.
, p. 51 - 56 (2010)
Three derivatives of ciprofloxacin (compound B, C, and D) were constructed utilizing microwave synthesis methodology (compound D) or diazoalkane reaction in nonaqueous solvent (compounds B and C). The final structures of the derivatives featured an ester group in place of the original carboxyl group of the ciprofloxacin. These ester groups contained aliphatic single carbon (compound B), two carbon length (compound C), or three carbon length propyl ester group (compound D). The ester groups strongly affected the molecular properties of the parent ciprofloxacin. As the size of the ester group increased the formula weight, molar volume, and number of rotatable bonds increased. The Log P for these compounds were -0.701, -0.441, -0.065, 0.437 for ciprofloxacin, B, C, and compound D, respectively. Numerical values of dermal permeability coefficient (Kp) increased rapidly as length of the ester carbon chain increased. The immediate consequence of Kp increase is an increased skin penetration rate based on dose and time span of administration. Polar surface area for ciprofloxacin is 74.569 Angstroms2, but decreases to 63.575 Angstroms2 for all three derivatives. All three derivatives of ciprofloxacin showed zero violations of the Rule of 5, indicating these drugs would have favorable bioavailability. Compounds A, B, C, and D were placed into tissue culture with methicillin resistant and susceptible Staphylococcus aureus (MRSA and MSSA, respectively) to determine levels of bacterial growth inhibition. All compounds induced greater than 60 % inhibition of MSSA at concentrations as low as 15.63 micrograms/milliliter. All four compounds induced greater than 80 % inhibition of MRSA at concentratins as low as 15.63 micrograms/milliliter. Development of novel drug designs will benefit the clinical treatment of dangerous infections of MSSA and MRSA.
Optimizing solubility and permeability of a biopharmaceutics classification system (BCS) class 4 antibiotic drug using lipophilic fragments disturbing the crystal lattice
Tehler, Ulrika,Fagerberg, Jonas H.,Svensson, Richard,Larhed, Mats,Artursson, Per,Bergstr?m, Christel A. S.
, p. 2690 - 2694 (2013)
Esterification was used to simultaneously increase solubility and permeability of ciprofloxacin, a biopharmaceutics classification system (BCS) class 4 drug (low solubility/low permeability) with solid-state limited solubility. Molecular flexibility was i
Enhancement of the antimalarial activity of ciprofloxacin using a double prodrug/bioorganometallic approach
Dubar, Faustine,Anquetin, Guillaume,Pradines, Bruno,Dive, Daniel,Khalife, Jamal,Biot, Christophe
, p. 7954 - 7957 (2009)
The derivatization of the fluoroquinolone ciprofloxacin greatly increases its antimalarial activity by combining bioorganometallic chemistry and the prodrug approach. Two new achiral compounds 2 and 4 were found to be 10- to 100-fold more active than ciprofloxacin against Plasmodium falciparum chloroquinesusceptible and chloroquine-resistant strains. These achiral derivatives killed parasites more rapidly than did ciprofloxacin. Compounds 2 and 4 were revealed to be promising leads, creating a new family of antimalarial agents.
Synthesis and antibacterial evaluation of a novel tricyclic oxaborole-fused fluoroquinolone
Li, Xianfeng,Zhang, Yong-Kang,Plattner, Jacob J.,Mao, Weimin,Alley,Xia, Yi,Hernandez, Vincent,Zhou, Yasheen,Ding, Charles Z.,Li, Jinpeng,Shao, Zhijun,Zhang, Hongwei,Xu, Musheng
, p. 963 - 966 (2013)
We have designed and synthesized a novel class of compounds based on fluoroquinolone antibacterial prototype. The design concept involved the replacement of the 3-carboxylic acid in ciprofloxacin with an oxaborole-fused ring as an acid-mimicking group. The synthetic method employed in this work provides a good example of incorporating boron atom in complex molecules with multiple functional groups. The antibacterial activity of the newly synthesized compounds has been evaluated.
Conjugation of ciprofloxacin with poly(2-oxazoline)s and polyethylene glycol via end groups
Schmidt, Martin,Harmuth, Simon,Barth, Eva Rebecca,Wurm, Elena,Fobbe, Rita,Sickmann, Albert,Krumm, Christian,Tiller, Joerg C.
, p. 1950 - 1962 (2015)
The antibiotic ciprofloxacin (CIP) was covalently attached to the chain end of poly(2-methyloxazoline) (PMOx), poly(2-ethyloxazoline) (PEtOx), and polyethylene glycol (PEG), and the antimicrobial activity of these conjugates was tested for Staphylococcus
On-Demand Continuous Manufacturing of Ciprofloxacin in Portable Plug-and-Play Factories: Development of a Highly Efficient Synthesis for Ciprofloxacin
Armstrong, Cameron,Miyai, Yuma,Formosa, Anna,Thomas, Dale,Chen, Esther,Hart, Travis,Schultz, Victor,Desai, Bimbisar K.,Cai, Angela Y.,Almasy, Alexandra,Jensen, Klavs,Rogers, Luke,Roper, Tom
supporting information, p. 1524 - 1533 (2021/07/21)
The experimental approach taken and challenges overcome in developing a high-purity production (>100 g) scale process for the telescoped synthesis of the antibiotic ciprofloxacin is outlined. The process was first optimized for each step sequentially with regard to purity and yield, with necessary process changes identified and implemented before scaling for longer runs. These changes included implementing a continuous liquid-liquid extraction (CLLE) step and eliminating and replacing the base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) initially used in the ring-closure step due to DBU plausibly forming a decomposition side product that negatively impacted the final product purity. Process conditions were scaled 1.5-2-fold in order to enable the ultimate project goal of producing enough crude ciprofloxacin within 24 h to manufacture 1000 250 mg tablets. Working toward this goal, several production-scale runs were carried out to assess the reproducibility and robustness of the finalized process conditions, with the first three steps being run continuously up to 22 h and the last two steps being run continuously up to 10 h. The end result is a process with a throughput of ～29 g/h (～700 g/24 h) with a crude product stream profile of 94 ± 2% and 34 ± 3 mg/mL after five chemical transformations across four reactors and one continuous CLLE unit operation with each intermediate step maintaining a purity >95% by HPLC.
PAT Implementation on a Mobile Continuous Pharmaceutical Manufacturing System: Real-Time Process Monitoring with In-Line FTIR and Raman Spectroscopy
Miyai, Yuma,Formosa, Anna,Armstrong, Cameron,Marquardt, Brian,Rogers, Luke,Roper, Thomas
supporting information, p. 2707 - 2717 (2021/12/13)
The strategies and experimental methods for implementation of process analytical technology (PAT) on the mobile pharmaceutical manufacturing system, Pharmacy on Demand (PoD), are discussed. With multiple processes to be monitored on the PoD end-to-end continuous manufacturing process, PAT and its real-time process monitoring capability play a significant role in ensuring final product quality. Here, we discuss PAT implementation for real-time monitoring of an intermediate and API concentrations with in-line Fourier-transformed infrared and Raman spectroscopy for the five-step continuous synthesis of ciprofloxacin on the PoD synthesis unit. Two partial least squares regression models were built and verified with flow chemistry experiments to obtain a root-mean-square error of prediction (RMSEP) of 2.2 mg/mL with a relative error of 2.8% for the step 2 FlowIR model and a RMSEP of 0.9 mg/mL with a relative error of 2.8% for the step 5 Raman model. These models were deployed during an 11 h step 1–3 and a 5 h step 4–5 continuous ciprofloxacin synthesis run performed on the PoD system. In these runs, the real-time prediction of intermediate and product concentration was achieved with an online model processing software (Solo_Predictor) and a PAT data collection and management software (synTQ).
Synthesis of Novel Ciprofloxacin-Based Hybrid Molecules toward Potent Antimalarial Activity
Dana, Srikanta,Dhar, Suman Kumar,Gurung, Sumiran Kumar,Kumar, Sharvan,Mondal, Neelima,Mukhopadhyay, Pritam,Valissery, Praveesh
supporting information, p. 1450 - 1456 (2020/08/14)
Antimalarial drug resistance is a serious obstacle in the persistent quest to eradicate malaria. There is a need for potent chemical agents that are able to act on drug-resistant Plasmodium falciparum populations at reasonable concentrations without any related toxicity to the host. By rational drug design, we envisaged to address this issue by generating a novel hybrid drug possessing two pharmacophores that can act on two unique and independent targets within the cell. We synthesized a new class of ciprofloxacin-based hybrid molecules, which have been integrated with acridine, quinolone, sulphonamide, and cinnamoyl pharmacophores (1-4). We realized a potent chloroquinolone-ciprofloxacin-based antimalarial hybrid (2, CQ-CFX) whose mechanism of action is unlike that of its parent molecules indicating a unique biological target. CQ-CFX is not only potent against CQ-resistant and susceptible strains of Plasmodium falciparum at low nanomolar concentrations (IC50 values are 63.17 ± 1.2 nM and 25.52 ± 4.45 nM, respectively) but is also not toxic to mammalian and bacterial systems up to 20 μM and 1 μM, respectively.
