Cytotoxic meroterpenoids from brown alga Stypopodium schimperi (Kutzing) Verlaque & Boudouresque with comprehensive molecular docking & dynamics and ADME studies
Küçük Resim Yok
Tarih
2024
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier Sci Ltd
Erişim Hakkı
info:eu-repo/semantics/closedAccess
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 (ER alpha), 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.
Açıklama
Anahtar Kelimeler
Stypopodium Schimperi, Secondary Metabolites, Cytotoxicity, Breast Cancer, Molecular Docking & Dynamics, Natural-Products, Meroditerpenoids, Flabelliforme, Triterpenoids, Derivatives, Epitaondiol, Inhibitors, Alkaloids
Kaynak
Process Biochemistry
WoS Q Değeri
N/A
Scopus Q Değeri
Q2
Cilt
136
