Triple-negative breast cancer suppressive activities, antioxidants and pharmacophore model of new acylated rhamnopyranoses from Premna odorata

• Published in: RSC advances 2020-03, Vol.10 (18), p.10584-10598
• Main Authors: Elmaidomy, Abeer H, Mohammed, Rabab, Owis, Asmsaa I, Hetta, Mona H, AboulMagd, Asmaa M, Siddique, Abu Bakar, Abdelmohsen, Usama Ramadan, Rateb, Mostafa E, El Sayed, Khalid A, Hassan, Hossam M
• Format: Article
• Language: English
• Subjects: Antioxidants; Aromatic compounds; Biotechnology; Breast cancer; Cell adhesion & migration; Chemistry; Free radicals; Hydrogen bonds; NMR; Nuclear magnetic resonance; Pharmacology; Scavenging; Two dimensional analysis; Wound healing
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d0ra01697g

Phytochemical investigation of Blanco "Lamiaceae" young stems afforded four new acylated rhamnopyranoses 1-4, along with fourteen known compounds 5-19. The structures of the new compounds were confirmed using extensive 1D, 2D NMR, and HRESIMS analysis. The isolated compounds were tested for their cell proliferation and migration inhibition activities against the invasive human triple-negative breast cancer cells MDA-MB-231 and MCF-7, and the normal human breast cell line MCF-10A. In addition, free radical scavenging activities using 2,2'-diphenyl-1-picrylhydrazyl (DPPH) were studied. Compound 1 was the most active as an antiproliferative agent, showing a high to moderate antiproliferative effect with an IC value of 4.95 and 17.7 μM against MCF-7 and MDA-MB-231, respectively. The antiproliferative activities of compounds 1-5 against the normal breast cell line MCF-10A were moderate to low with IC values of 13.91 to 27.70 μM. On the other hand, compounds 1 and 10 suppressed MDA-MB-231 cell migration in the wound-healing assay at 10 μM concentration. Meanwhile, compounds 1-5 exhibited the highest value of DPPH radical scavenging activities with an IC value range of 17.5-20.43 ± 0.5 μg mL . The pharmacophore model generated using Molecular Operating Environment (MOE) for compounds 1-5 showed three hydrogen bond acceptors (HBAs), one hydrogen bond donor (HBD), one aromatic ring (Aro), and one hydrophobic (Hyd.) group. The central HBA feature lies at a distance of 4.36 Å and 6.38 Å from the remaining two HBA features. Also, the HBD feature maintains a distance of 2.74 Å from the aromatic feature. Acylated rhamnopyranoses can be considered good scaffolds for developing new anti-breast cancer and antioxidant compounds.