57152-56-4Relevant academic research and scientific papers
Chiral separation and modeling of quinolones on teicoplanin macrocyclic glycopeptide antibiotics CSP
Ali, Imran,Suhail, Mohd,Asnin, Leonid
, p. 1304 - 1311 (2018/10/24)
New chiral high-performance liquid chromatography (HPLC) method for the enantiomeric resolution of quinolones is developed and described. The column used was Chirobiotic T (150?×?4.6?mm, 5.0?μm). Three mobile phases used were MeOH:ACN:Water:TEA (70:10:20:0.1%), (60:30:10:0.1%), and (50:30:20:0.1%). The flow rate of the mobile phases was 1.0?mL/min with UV detection at different wavelengths. The values of retention, resolution, and separation factors ranged from 1.5 to 6.0, 1.80 to 2.25, and 2.86 to 6.0, respectively. The limit of detection and quantification ranged from 4.0 to 12?ng and 40 to 52?ng, respectively. The modeling studies indicated strong interactions of R-enantiomers with teicoplanin chiral selector than S-enantiomers. The supra molecular mechanism of the chiral recognition was established by modeling and chromatographic studies. It was observed that hydrogen bondings and π-π interactions are the major forces for chiral separation. The present chiral HPLC method may be used for enantiomeric resolution of quinolones in any matrices.
Scalable preparation and differential pharmacologic and toxicologic profiles of primaquine enantiomers
Nanayakkara, N. P. Dhammika,Tekwani, Babu L.,Herath, H. M. T. Bandara,Sahu, Rajnish,Gettayacamin, Montip,Tungtaeng, Anchalee,Van Gessel, Yvonne,Baresel, Paul,Wickham, Kristina S.,Bartlett, Marilyn S.,Fronczek, Frank R.,Melendez, Victor,Ohrt, Colin,Reichard, Gregory A.,McChesney, James D.,Rochford, Rosemary,Walker, Larry A.
, p. 4737 - 4744 (2014/08/18)
Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) activity is the major limitation of primaquine (PQ), the only antimalarial drug in clinical use for treatment of relapsing Plasmodium vivax malaria. PQ is currently clinically used in its racemic form. A scalable procedure was developed to resolve racemic PQ, thus providing pure enantiomers for the first time for detailed preclinical evaluation and potentially for clinical use. These enantiomers were compared for antiparasitic activity using several mouse models and also for general and hematological toxicities in mice and dogs. (+)-(S)-PQ showed better suppressive and causal prophylactic activity than (-)-(R)-PQ in mice infected with Plasmodium berghei. Similarly, (+)-(S)-PQ was a more potent suppressive agent than (-)-(R)-PQ in a mouse model of Pneumocystis carinii pneumonia. However, at higher doses, (+)-(S)-PQ also showed more systemic toxicity for mice. In beagle dogs, (+)-(S)-PQ caused more methemoglobinemia and was toxic at 5 mg/kg of body weight/day given orally for 3 days, while (-)-(R)-PQ was well tolerated. In a novel mouse model of hemolytic anemia associated with human G6PD deficiency, it was also demonstrated that (-)-(R)-PQ was less hemolytic than (+)-(S)-PQ for the G6PD-deficient human red cells engrafted in the NOD-SCID mice. All these data suggest that while (+)-(S)-PQ shows greater potency in terms of antiparasitic efficacy in rodents, it is also more hematotoxic than (-)-(R)-PQ in mice and dogs. Activity and toxicity differences of PQ enantiomers in different species can be attributed to their different pharmacokinetic and metabolic profiles. Taken together, these studies suggest that (-)-(R)-PQ may have a better safety margin than the racemate in human. Copyright
