Chromatographic separation and biological evaluation of benzimidazole derivative enantiomers as inhibitors of leukotriene biosynthesis

Sardella R., Levent S., Ianni F., ÇALIŞKAN B., Gerstmeier J., Pergola C., ...Daha Fazla

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, cilt.89, ss.88-92, 2014 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 89
  • Basım Tarihi: 2014
  • Doi Numarası: 10.1016/j.jpba.2013.10.039
  • Dergi Adı: JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.88-92
  • Anahtar Kelimeler: Chromatographic enantioisolation, Polysaccharide-based stationary phases, 5-Lipoxygenase-activating protein, FLAP, Benzimidazole, CHIRAL STATIONARY PHASES, 5-LIPOXYGENASE-ACTIVATING PROTEIN, AMYLOSE, FLAP, ENANTIORESOLUTION, SELECTIVITY, ADDITIVES, POTENT
  • Gazi Üniversitesi Adresli: Evet

Özet

For an explicit analysis of the chirality on the effectiveness of a recently identified racemic benzimidazole derivative (BRP7) as inhibitor of leukotriene biosynthesis, we optimized a HPLC-based chiral chromatographic method enabling the quantitative isolation of its enantiomers in sufficient amount to carry out biological investigations. The use of a Lux Amylose-2 column revealed especially profitable to fulfil our task. Indeed, the employment of the amylose-based chiral stationary phase (CSP) in combination with a n-hexane/EtOH/DEA - 99/1/02 (v/v/v) mobile phase allowed getting the enantiomeric peaks fully resolved (alpha = 1.80, R-S = 2.39). Four consecutive injections repeated at 1-min intervals produced overloaded peaks with a very limited level of isomeric contamination. This procedure allowed the isolation of ca. 20 mg of each enantiomer, with enantiomeric excess higher than 99% and 95% for the (S)- and the (R)-isomer, respectively. The enantiomeric elution order was established using synthetic reference compounds of lower enantiomeric excess values. The biological evaluation of the purified individual enantiomers revealed no significant difference in terms of their IC50 values with respect to the previously investigated racemic BRP7: 0.18 mu M for the (R)-enantiomer (R-2 = 0.999) and 0.26 mu M for the (S)-enantiomer (R-2 = 0.986). (C) 2013 Elsevier B.V. All rights reserved.