Bioactivity and molecular docking of lactones isolated from Centaurea pseudosinaica Czerep

Fatima B Alamri; Tariq R Sobahi; Hanan I Althagbi; Ahmed Abdel-Lateff; Mohammed Y Alfaifi; Ayeda Y Mohammed; Ehab Abdel-Latif; Walied M Alarif

doi:10.1016/j.jsps.2023.04.017

Bioactivity and molecular docking of lactones isolated from Centaurea pseudosinaica Czerep

Saudi Pharm J. 2023 Jun;31(6):773-782. doi: 10.1016/j.jsps.2023.04.017. Epub 2023 Apr 23.

Authors

Fatima B Alamri¹, Tariq R Sobahi¹, Hanan I Althagbi², Ahmed Abdel-Lateff³, Mohammed Y Alfaifi⁴, Ayeda Y Mohammed⁵, Ehab Abdel-Latif⁶, Walied M Alarif⁷

Affiliations

¹ Department of Chemistry, Faculty of Science, King Abdulaziz University, PO. Box 80203, Jeddah 21589, Saudi Arabia.
² Department of Chemistry, College of Science, University of Jeddah, Jeddah 21589, Saudi Arabia.
³ Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
⁴ Department of Biology, Faculty of Science, King Khalid University, Abha 9004, Saudi Arabia.
⁵ Department of Chemistry, Faculty of Science and Art, Najran University, Najran 11001, Saudi Arabia.
⁶ Department of Chemistry, Faculty of Science, Mansoura University, Mansoura 35516, Egypt.
⁷ Department of Marine Chemistry, Faculty of Marine Sciences, King Abdulaziz University, PO. Box 80207, Jeddah 21589, Saudi Arabia.

Abstract

Two cytotoxic sesquiterpene lactones, 17-epichlorohyssopifolin A (1) and chlorjanerin (2), and a monoterpene lactone, loliolide (3) were isolated from Centaurea pseudosinaica. The cytotoxicity of the total extract and terpenoids 1-3 were evaluated against three human cancer cells (HepG2, PC-3, and HT-29), along with the human normal primary epidermal keratinocytes (HEKa) cells. With IC₅₀ values ranging between 0.6 ± 0.04 and 5.0 ± 0.61 μg/mL against HepG2; 0.2 ± 0.01 and 11.9 ± 1.31 μg/mL against PC-3, and 0.04 ± 0.013 and 8.9 ± 0.97 μg/mL against HT-29, the total extract, and lactones 1-3 demonstrated cytotoxic effects. Compound 1 displayed the strongest impact on all cancer cells and a slightly safe effect on the normal cells HEKa. Compound 1 caused accumulation of HepG2 and HT-29 cells in G1 phase as displayed cell cycle analysis. On the other hand, the cell distributions were increased in the S phase in PC-3 cells. Furthermore, 1 caused apoptosis in PC-3 and HePG2 cells with 91.50%, and 79.72 %, respectively. A higher fraction of necrotic cells was observed in HT-29 cells amounting to 23.60%. These results suggested that the promising cytotoxicity exhibited by 1 is brought by the apoptosis induction in the cancer cells, which were evaluated. As the compounds showed antiproliferative effect against the HT-29 cells, the docking simulation was performed aiming at determining how they would interact with the EGFR enzyme, whose PDB: 4I23 is considered one of the two distinct wild types of EGFR enzymes. The antibacterial activity results revealed that 3 showed the most remarkable antibacterial effects, especially against the examined Gram-positive bacteria. The total extract exhibited potent activity against all examined bacteria. The total extract showed a potent antifungal effect against two Candida and two Aspergillus pathogens. The antioxidant activity revealed the potency of the total extract and 3 as antioxidant candidates. The obtained results refer to the importance of Centaurea pseudosinaica as a source of potent antiproliferative agents and the whole plant as an antipathogenic and antioxidant agent.

Keywords: Antioxidants; Antipathogens; Antiproliferation; Asteraceae; Mono- and sesquiterpene lactones.