Inhibition of Human Colorectal Cancer by a Natural Product 7-Acetylhorminone and Interactions with BSA/HSA: Multispectral Analysis and In Silico and In Vitro Studies.
Sourav PakrashySouvik ChakrabortySounik MannaJuli Nanda GoswamiBiswajit BhattacharyaFranziska EmmerlingJishu MandalSourav MisraSujata Maiti ChoudhuryMohammad K OklaAdity BosePawan Kumar MauryaAnjoy MajhiMalay DolaiPublished in: ACS applied bio materials (2024)
We have semi-synthesized a natural product 7-acetylhorminone from crude extract of Premna obtusifolia (Indian headache tree), which is active against colorectal cancer after probation through computational screening methods as it passed through the set parameters of pharmacokinetics (most important nonblood-brain barrier permeant) and drug likeliness (e.g., Lipinski's, Ghose's, Veber's rule) which most other phytoconstituents failed to pass combined with docking with EGFR protein which is highly upregulated in the colorectal carcinoma cell. The structure of 7-acetylhorminone was confirmed by single crystal X-ray diffraction studies and 1 H NMR, 13 C NMR, and COSY studies. To validate the theoretical studies, first, in vitro experiments were carried out against human colorectal carcinoma cell lines (HCT116) which revealed the potent cytotoxic efficacy of 7-acetylhorminone and verified preliminary investigation. Second, the drugability of 7-acetylhorminone interaction with serum albumin proteins (HSA and BSA) is evaluated both theoretically and experimentally via steady-state fluorescence spectroscopic studies, circular dichroism, isothermal titration calorimetry, and molecular docking. In summary, this study reveals the applicability of 7-acetylhorminone as a potent drug candidate or as a combinatorial drug against colorectal cancer.
Keyphrases
- molecular docking
- case control
- endothelial cells
- high resolution
- molecular dynamics simulations
- magnetic resonance
- single cell
- stem cells
- epidermal growth factor receptor
- induced pluripotent stem cells
- mesenchymal stem cells
- white matter
- pluripotent stem cells
- molecular dynamics
- mass spectrometry
- brain injury
- oxidative stress
- solid state
- emergency department
- adverse drug
- tyrosine kinase
- bone marrow
- computed tomography
- amino acid
- cerebral ischemia