Cytotoxic activity, molecular docking, pharmacokinetic properties and quantum mechanics calculations of the brown macroalga <i>Cystoseira trinodis</i> compounds
Shimaa A. Ahmed, Shimaa A. Ahmed, Aziz Abdur Rahman, Khaled N. M. Elsayed, H. R. Abd El-Mageed, Hussein S. Mohamed, Sayed A. Ahmed, Sayed A. Ahmed
Abstract
In this study, nine compounds were isolated, eight of them were isolated for the first time from Cystoseira trinodis. The biological activity of the extract, fractions and pure compounds was evaluated. The antimicrobial activity was investigated against 3 fungi species, 3 gram + ve and 3 gram –ve bacteria. The crude extract and fractions showed moderate inhibition against some of the tested microorganisms, especially the butanol fraction exhibited the maximum inhibition zone against Salmonella typhimurium (16 ± 0.60 mm). Cytotoxicity was evaluated against HepG-2 and MCF-7 cell lines. Hexane fraction exhibited the highest cytotoxic effect against HepG-2 and MCF-7 cell lines with an IC50 value of 14.3 ± 0.8 and 19.2 ± 0.7 µg/ml, respectively with compared to other fractions. The isolates were identified as octacosanoic acid (1), glyceryl trilinoleate (2), oleic acid (3), and the epimeric mixture of saringosterols (4, 5), β-sitosterol (6), glycoglycerolipid (7) and a mixture of kjellmanianone and loliolide (8, 9) by spectroscopic analysis. Among the all tested compounds kjellmanianone and loliolide mixture exhibited significant cytotoxic activity with an IC50 value of 7.27 µg/ml against HepG-2 cells. The major and minor constituents of the extract and fractions were identified using GC-MS analysis. Molecular docking analysis confirmed that most of the studied compounds especially compounds 8 and 9 strongly interact with TPK and VEGFR-2 with highest binding energies supported that the high cytotoxicity of these compounds against human hepatocellular cancer in the experimental part. The energetic, geometric and topological properties of compounds 8 and 9 binding with cytosine base were computed by DFT methods. Molecular properties descriptors, bioactivity score and ADMET analysis confirmed that most of the studied compounds especially compounds 8 and 9 exhibit significant biological activities and have a better chance to be developed as drug leads. Communicated by Ramaswamy H. Sarma