## 4 Discussion
Thereafter, the absolute configuration for gracilioether M (**6**) and 11,12-dihydroracilioether M (7) at C6 and C10 could be inferred following a similar strategy. In the first place, we successfully transformed compounds **6** and **7** into plaktortone G (**9**) and 9,10-dihydroracilio G (**8**), respectively, through chemoselective PCC oxidative cleavage, as outlined by [PERSON] [23] [PCC (0.03 mmol), 4 A MS (10.0 mg), 1,2-dichloroethane (10 mL), reflux 15 h]. Since we had already succeeded at converting **6** into **7** by selective catalytic hydrogenation, the **6**\(\Rightarrow\)**9** and **7**\(\Rightarrow\)**8** degradations effectively established the absolute stereochemistry of all the new compounds. A summary of all the chemical interconversions conducted during this investigation is shown in Scheme 1. In the second place, in so far as the configurational assignments for the \(\Delta^{2}\) and \(\Delta^{11}\) olefins in **6** (or \(\Delta^{2}\) in **7**) are concerned, we used the following strategy: The (\(Z\))-geometry shown at \(\Delta^{2}\) in **6** and **7** was based on the presence of strong nuclear Overhauser effect (NOE) interactions between the protons attached to C2 and C15 (Figure 5). Regarding the geometry of \(\Delta^{11}\) in **6**, the large coupling constant (15.1 Hz) detected between protons H11 and H12 combined with the conspicuous absence of NOEs between them support the (\(E\))-geometry. Figure 5: Selected NOE interactions observed in the 2D NOESY spectra for gracilioether M (**6**). Arguably, the lack of activity of **6-9** against _P. berghei_ might be attributed to the absence of an endoperoxide ring system in them. Prior research has consistently highlighted the pivotal role of this specific structural feature in conferring antimalarial activity [36,37]. The endoperoxide ring system is known for its ability to generate reactive oxygen species within the parasite's cells, ultimately leading to the destruction of the malaria-causing pathogen [38, 39, 40, 41]. Hence, the absence of this moiety in compounds **6** and **7** and the mixture of **8** and **9** aligns favorably with the observed lack of activity against the malaria parasite. This finding underscores the importance of the endoperoxide motif in the design and development of antimalarial agents and provides valuable insights for future research in this field. As far as our in vitro cell viability experiments are concerned, we noticed that our data revealed that none of the tested natural marine products exhibited discernible anticancer activity against the cell line used throughout this work. The reduced effectiveness of compounds **6-9** against MCF-7 cells may be explained by the absence of hydrophilicity in their molecular structures. This contrasts with letrozole (**10**), which contains several nitrile and 1H-1,2,4-triazole groups, as indicated in Figure 4. These functional groups within structure **10** provide multiple sites for potential interactions through hydrogen bonding within the enzyme pocket site of MCF-7 cells [42]. The observation regarding a plausible hydrophilic binding in the enzyme pocket site of MCF-7 cells finds support in the fact that several natural marine products, renowned for their remarkable anticancer activity against this breast cancer cell line, exhibit even lower \(\text{IC}_{50}\) values than those reported for letrozole (**10**), since they also feature highly hydrophilic functional groups throughout their molecular structures. For instance, 2,2-bis(6'-bromo-3'-indolyl)ethylamine (**11**), an alkaloid that was isolated for the first time from the marine tunicate _Didemmum candidum_[43] and later reisolated from the marine sponge _Gellius sp._, demonstrated an \(\text{IC}_{50}\) of 3.4 \(\upmu\)M against MCF-7 cells [44].