Cytotoxic meroterpenoids from brown alga Stypopodium schimperi (Kützing) Verlaque & Boudouresque with comprehensive molecular docking & dynamics and ADME studies

DEMİRKIRAN Ö., EROL E., ŞENOL H., Kesdi İ. M., ALİM TORAMAN G. Ö., OKUDAN E. Ş., ...Daha Fazla

Process Biochemistry, cilt.136, ss.90-108, 2024 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 136
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1016/j.procbio.2023.11.029
  • Dergi Adı: Process Biochemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Aqualine, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, Compendex, Food Science & Technology Abstracts, INSPEC, Metadex, Pollution Abstracts, Veterinary Science Database, Civil Engineering Abstracts
  • Sayfa Sayıları: ss.90-108
  • Anahtar Kelimeler: Breast cancer, Cytotoxicity, Molecular docking & dynamics, Secondary metabolites, Stypopodium schimperi
  • Akdeniz Üniversitesi Adresli: Evet

Özet

In this study, five known meroterpenoids sargaol (1), flabellinone (2), stypodiol (3), atomarianone A (4), atomarianone B (5), and a known steroid fucosterol (6) were isolated from brown alga Stypopodium schimperi. Their structures were elucidated by 1D- and 2D NMR and mass spectroscopic analyses. Isolated compounds were tested against human healthy fibroblast cells (CCD-1079Sk), and two different types of human breast cancer cell lines (MDA-MB-231 and MCF-7). They were also investigated by molecular docking studies on estrogen receptor alpha (ERα), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2), cyclin-dependent kinases 2, 4 and 6 (CDK2/4/6) proteins. Molecular dynamics simulations were carried out to determine their ligand-protein stability and binding affinity. The four isolates (1-3, 6) showed strong cytotoxic activity in vitro against both cancer cell lines, particularly the aggressive MDA-MB-231 cell line, which was verified by in silico screening. Fucosterol was found to be the most selective compound against cancer cell lines, particularly the aggressive MDA-MB-231 cell line with a selectivity index (SI>16). The ADME prediction was also carried out and all the isolate compounds showed drug likeness. As a result, stypodiol and fucosterol were found to be the most potent compounds against both cancer cell lines by in vitro and in silico studies.