Amberboin and lipidiol: X-ray crystalographic data, absolute configuration and inhibition of cholinesterase


Elsebai M. F., Ghabbour H. A., Marzouk A. M., Salmas R. E., ERDOĞAN ORHAN İ., ŞENOL DENİZ F. S.

PHYTOCHEMISTRY LETTERS, cilt.27, ss.44-48, 2018 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 27
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1016/j.phytol.2018.06.023
  • Dergi Adı: PHYTOCHEMISTRY LETTERS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.44-48
  • Anahtar Kelimeler: Amberboin, Lipidiol, Volutaria abyssinica, Natural products, Acetylcholinesterase, Butyrylcholinesterase, Molecular modeling, HEPATITIS-C VIRUS, DISCOVERY, LACTONES, PROTEIN
  • Lokman Hekim Üniversitesi Adresli: Hayır

Özet

The phytochemical investigation of the extract of Volutaria abyssinica (A. Rich.) C. Jeffrey (Asteraceae) resulted in the identification of the two sesquiterpene lactones, i.e. amberboin and lipidiol. Amberboin and lipidiol are interesting tricyclic sesquiterpene lactone derivatives with a guaianolide skeleton. In the current study, the absolute structure and absolute configuration of amberboin were determined for the first time. The structure of amberboin was unambiguously determined with the single crystal X-ray measurements and the absolute configuration of the seven chiral centers was determined to be C2(R), C3(R), C4(S), C7(R), C10(S), C11(R) and C12(R). The biological investigation of both compounds 1 and 2 against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) showed that both compounds are promising inhibitors of AChE with IC50 values of 0.79 +/- 0.03 mu M and 0.52 +/- 0.01 mu M for amberboin and lipidiol, respectively, while amberboin (IC50 = 0.58 +/- 0.13 mu M) also effectively inhibited BChE. Additionally, in order to get a better understanding of the inhibition mechanism and also the crucial amino acids contributing to the interactions between the ligands and protein atoms, the catalytic domains of the complexes were studied using molecular modeling approaches. The results suggested that the ligands were quite accommodated inside the binding domains and able to form strong polar and nonpolar contacts with the active site amino acids.